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Biomedical subjects

S A Moser

Publications and source records attributed to S A Moser.

At least 37 records · Page 2Linked to original sources

Cytokine involvement in immunomodulatory activity affected by Candida albicans mannan.

Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates the production of splenic CD8+ effector cells which downregulate delayed hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction and/or elicitation of downregulation was studied by (i) examining murine splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, and gamma interferon (IFN-gamma), (ii) quantitating splenocyte mRNA for IL-12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii) measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked immunosorbent assay, each performed at selected intervals over 96 h after giving MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h period, whereas those for IL-4 and IFN-gamma were either weak or undetectable prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the downregulatory effect of MAN only when given at the time of MAN administration. Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at 48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s) for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-gamma, interacting with MAN-activated cells in the absence of biologically active IL-12, may induce the production of CD8+ downregulatory effector cells. Partial abrogation of downregulatory activity in animals treated with anti-IL-4 at the time of induction of such activity lends support to this hypothesis.

Animals↗

Comparison of the MB/BacT system with a revised antibiotic supplement kit to the BACTEC 460 system for detection of mycobacteria in clinical specimens.

The MB/BacT system (MB/BacT) with a revised antibiotic supplement kit was compared with the BACTEC 460 system (BACTEC 460) in a test of 488 specimens submitted for mycobacterial culture from 302 patients. Twenty-four Mycobacterium tuberculosis isolates were detected by the BACTEC 460 versus 23 isolates by the MB/BacT. Mean time until detection of M. tuberculosis isolates identified by both systems was 11.9 days for the BACTEC 460 versus 13.7 days for the MB/BacT (P = 0.046). M. avium complex was detected in 12 specimens by the MB/BacT versus 10 specimens by the BACTEC 460. Only 8 of 14 (57%) M. avium isolates were detected by both systems, with a mean time until detection of 10.1 days for the BACTEC 460 and 14.2 days for the MB/BacT (P = 0.009). The BACTEC 460 and the MB/BacT detected M. gordonae in four specimens, but only a single specimen was positive by both systems. One M. fortuitum isolate and one of five M. kansasii isolates were recovered only by the BACTEC 460. The bacterial overgrowth rate was 7.0% for the MB/BacT versus 4.1% for the BACTEC 460. We found the MB/BacT to be comparable to the BACTEC 460 for mycobacterial detection. Even though time until detection with the MB/BacT was slightly longer (1.8 days longer for M. tuberculosis and 4.1 days for M. avium [mean values]) and the bacterial overgrowth rate was somewhat higher, the decreased labor, the availability of a computerized data management system, and the noninvasive, nonradiometric aspects of the MB/BacT offset these relative disadvantages and make it an acceptable alternative for use in the diagnostic laboratory.

Anti-Bacterial Agents↗

Direct susceptibility testing with positive BacT/Alert blood cultures by using MicroScan overnight and rapid panels.

Studies were conducted on a method of direct inoculation of MicroScan dried overnight and of rapid panels with positive aerobic blood cultures obtained from the BacT/Alert to determine antimicrobial susceptibilities. Inocula were limited to specimens that appeared unimicrobic on Gram stain. Results were compared to those obtained from panels inoculated following subculture. For 133 gram-negative bacilli, there were 94.7 and 93.5% categorical agreements between direct and standard methods for all drugs tested with overnight and rapid panels, respectively. For 104 gram-positive cocci, there were 93.2 and 93.1% categorical agreements for overnight and rapid panels, respectively. The major error (false resistance) rate for gram negatives was 1.4% for overnight versus 0.7% for rapid panels. The very major error (false susceptibility) rate was 2.7% for overnight versus 8.1% for rapid panels. The total error rates were 1.6% for overnight panels and 1.5% for rapid panels. The major error rates for gram-positive direct susceptibility tests were 2.6% for overnight and 2.5% for rapid panels. The very major error rates were 8.8 and 7.2% for overnight and rapid panels, respectively. Total error rates were 3.6% for overnight and rapid gram-positive panels. These findings suggest that susceptibility results obtained from directly inoculated gram-negative overnight panels have the greatest correlation to those obtained by standard methods. When discrepant results occur with direct-susceptibility testing, they are more likely to show false susceptibility than false resistance.

Aerobiosis↗

Pathology information systems: data mining leads to knowledge discovery.

Information systems in pathology provide opportunities for pathologists and clinical laboratory scientists to impact both clinical care and modern research agendas. The paradigm shift in health care from individualized care to population-based and standardized delivery systems has created both of these opportunities. In research, pathology information systems can provide key databases for health services research and new informatics-based approaches to database research. The latter is characterized by utilization of pathology databases for data mining to discover new patterns that provide new knowledge. The multidisciplinary knowledge discovery and data mining program at the University of Alabama at Birmingham focuses on this health care application, which has the potential to make a major impact on health care research and delivery.

Artificial Intelligence↗

Genotypic investigation of multidrug-resistant Acinetobacter baumannii infections in a medical intensive care unit.

Multi-resistant Acinetobacter baumannii isolates obtained from 13 hospitalized patients over a six-month period were evaluated. One patient had an isolate susceptible only to imipenem; the next three had isolates susceptible to imipenem and ampicillin/sulbactam; the next six patients had isolates which were susceptible to imipenem, amikacin, and ampicillin/sulbactam; while the final three patients had isolates which were susceptible to imipenem and ampicillin/sulbactam. Ten patients died, five within 10 days of a positive culture. Five of six patients with bacteraemia succumbed to the infection. DNA extracted from all isolates was amplified by polymerase chain reaction using four random primers (RAPD). The resulting band patterns were compared and strains identified. In addition, all isolates were biotyped. RAPD analysis and biotyping showed that there were two distinct strains involved. The first four patients were infected with one strain (genotype ¿A', biotype 9), the subsequent nine patients were infected with a second strain (genotype ¿B', biotype 1). These results suggested that there was patient-to-patient spread of strains. Institution of, and strict adherence to, isolation procedure and other infection control practices controlled the spread of infection. These data emphasize the need for active surveillance for multidrug-resistant organisms in critically ill patients, and the value of molecular typing of strains in a hospital setting to investigate spread of infection.

Acinetobacter↗

Alterations to the cell wall of Histoplasma capsulatum yeasts during infection of macrophages or epithelial cells.

Many Histoplasma capsulatum strains have alpha-(1,3)-glucan in their cell walls and spontaneously produce variants that lack this polymer. The variants, in contrast to the parents, exist in aberrant shapes within macrophages. Here, the ultrastructure of the parental and variant cell walls was examined. All yeasts had identical electron-lucent, thick walls when grown in broth culture. However, ingestion by either macrophages or hamster trachea epithelial (HTE) cells caused the walls of variants to become electron-dense, thin, and sinuous. Parental strains remained unchanged in macrophages. Within HTE cells inoculated with parental strains, some organisms retained a thick wall and alpha-(1,3)-glucan but appeared to be degrading. In contrast, apparently intact intracellular yeasts had thin, wavy walls lacking alpha-(1,3)-glucan. A microenvironment within HTE cells that is unfavorable for the parental phenotype may trigger this ultrastructural change, potentially explaining why only variant yeasts are harvested from such cultures.

Animals↗

Comparative in vitro antimicrobial susceptibilities of nosocomial isolates of Acinetobacter baumannii and synergistic activities of nine antimicrobial combinations.

The in vitro susceptibilities of 69 nosocomial Acinetobacter isolates were determined by the broth microdilution method. Fourteen (20%) isolates were resistant to at least two aminoglycosides and two extended-spectrum penicillins. Nine antimicrobial combinations were then tested for synergy against these 14 isolates by checkerboard titration: imipenem with ciprofloxacin, amikacin, and tobramycin and ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate with amikacin and tobramycin. Synergy was detected with one or more antimicrobial combinations against 9 of 14 (64%) isolates, partial synergy was detected with one or more combinations against all 14 isolates, and an additive effect alone was observed with two different combinations against two isolates. No antagonism was detected with any combination. Imipenem plus either amikacin or tobramycin resulted in a synergistic or partial synergistic response against all 14 isolates. Specific combinations showing synergy against A. baumannii isolates were imipenem with tobramycin (four isolates), imipenem with amikacin (three isolates), ampicillin-sulbactam with tobramycin (six isolates), ampicillin-sulbactam with amikacin (three isolates), and ticarcillin-clavulanate with tobramycin (one isolate). Genotyping by randomly amplified polymorphic DNA analysis showed that 9 of the 14 isolates were of one strain, 4 isolates were of a second strain, and the remaining isolate was of a different strain. Eight of 14 (57%) patients infected with resistant A. baumannii isolates died. Only 3 of 14 patients had received a therapeutic regimen which was tested for synergy. Clinical studies are needed to determine the significance of these findings.

Acinetobacter↗

Detection of oxacillin-resistance in Staphylococcus aureus by MicroScan MIC panels in comparison to four other methods.

Two hundred fifty-two isolates of Staphylococcus aureus were tested for oxacillin susceptibility by MicroScan Gram positive overnight and rapid MIC panels. Results were compared with nonautomated methods including disk diffusion, MRSA Crystal ID, and Etests using MRSA Screen Agar as reference. One hundred sixty-nine isolates (67.1%) were oxacillin-susceptible and 83 (32.9%) were resistant. All methods agreed for 234 (92.9%) isolates. Very major error rates were 1.2% for disk diffusion, 3.6% for Etest, and 0 for all other methods. Major error rates were 5.3% for MicroScan overnight panels, 3% for rapid panels, 2.4% for disk diffusion, 1.2% for Etest, and 0.6% for MRSA Crystal ID. Nine oxacillin-susceptible isolates with borderline MICs and discrepant results for 1 or more methods were tested for the mec A gene and all were negative. Each was susceptible to beta lactam/beta lactamase inhibitor combinations, suggesting that false resistance may have been due to excessive beta lactamase production. Oxacillin-resistant S. aureus with borderline MICs determined by MicroScan should be confirmed by an alternate method. The most practical and cost-effective means among those we tested is the MRSA Screen Agar.

Diffusion↗

Usefulness of follow-up electrophysiologic study and event monitoring after successful radiofrequency catheter ablation of supraventricular tachycardia. Atakr Multicenter Investigators Group.

We assessed the usefulness of routine follow-up electrophysiologic studies after successful catheter ablation for supraventricular tachycardia and the role of event monitoring as an alternative modality in 310 patients at 11 centers using an investigational catheter ablation system with closed-loop temperature control. A routine follow-up electrophysiologic study between 1 and 3 months after ablation was required as part of the study protocol, and patients developing palpitations after ablation were encouraged to use event monitors. Recurrence of the initially targeted arrhythmia developed in 23 patients (7.4%) at a mean of 1.5 +/- 1.5 months after ablation. However, only 2 of these 23 recurrences were discovered by routine follow-up electrophysiologic study in asymptomatic patients (both with concealed accessory pathways); in the remaining 21 patients a positive follow-up electrophysiologic study was heralded by either recurrent symptoms, documented recurrent supraventricular tachycardia, and/or preexcitation on the electrocardiogram. Eighteen patients complained of palpitations after ablation and received an event monitor, which correctly diagnosed another cause of palpitations and ruled out recurrence of the ablated arrhythmia in 8 patients. Thus, the combination of clinical follow-up and event monitoring appears to be an effective alternative to routine follow-up electrophysiologic studies after catheter ablation of supraventricular tachycardia.

Adolescent↗

Comparison of four DNA-based methods for strain delineation of Candida lusitaniae.

Four methods for the accurate delineation of epidemiologically related and unrelated strains of Candida lusitaniae were compared. Three pulsed-field electrophoretic methods, including two contour-clamped homogeneous field gel electrophoresis methods (EKP-1 and EKP-2) yielding electrophoretic karyotype patterns of intact chromosomal DNA and a method in which the chromosomal DNA was macrodigested with the endonuclease SfiI prior to pulsed-field electrophoresis (MDP), and a random amplified polymorphic DNA (RAPD) assay were evaluated. A selected panel of 21 well-characterized isolated representing 13 strains of C. lusitaniae, including 7 epidemiologically related isolates of one strain (group I-A), 3 epidemiologically related isolates of another strain (group I-B), and 11 epidemiologically unrelated isolates (group II), were tested. All isolates were coded and tested in a blinded manner. All seven group I-A isolates were confirmed to be a single strain by the EKP-1 and MDP methods, and the three group I-B isolates were shown to be a single strain by the EKP-1, EKP-2, MDP, and RAPD methods. Subtle differences were noted with two of the group I-A isolates by the EKP-2 method, whereas three of these isolates were different by the RAPD method. Each group II isolate had distinct patterns by all four methods. These data support the fact that the three pulsed-field electrophoretic methods and the RAPD method can be used to delineate strains of C. lusitaniae. The EKP-1, EKP-2, and MDP gave results that correlated with the epidemiologic characteristics of the isolates tested in the study, whereas the RAPD method was perhaps too sensitive in detecting DNA changes for epidemiologic studies.

Candida↗

Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia.

Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis conida produces chronic pulmonary and disseminated blastomycosis characterized by pyogranulomatous inflammation. To study the evolution of the pulmonary infection, mice were killed at varying intervals after inoculation, their lungs cultured and examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas, which developed first as central microabscesses associated with a peripheral zone of M phi and giant cells containing internalized yeast, were a prominent feature of the infection. Lymphocytic and plasmacytic infiltrates, accumulating next to granulomas, formed the major peripheral component of the granuloma by Day 35. Formation of pyogranulomas was coincident with the host's failure to contain fungal growth measured by the sharp rise in colony-forming units recovered from lungs. Antibody against B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion. During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data contribute to our knowledge of this model and help form the basis for investigations into the roles of fungal pathogenic and host defense mechanisms in blastomycosis.

Animals↗

Interleukin-1 is linked to the respiratory epithelial cytopathology of pertussis.

Bordetella pertussis, the causative agent of whooping cough, releases a muramyl peptide known as tracheal cytotoxin (TCT) that is responsible for destruction of ciliated epithelial cells lining the large airways. In vitro, TCT has been shown to cause this specific pathology in human or hamster respiratory epithelium and to inhibit the proliferation of cultured hamster trachea epithelial cells. The diverse biological actions of muramyl peptides, including adjuvanticity, somnogenicity, and pyrogenicity, have been correlated with the production and release of the inflammatory mediator interleukin-1 (IL-1). Consistent with its ability to reproduce other muramyl peptide actions, recombinant IL-1 caused TCT-like damage to the respiratory epithelium. In the nanogram-per-milliliter range, exogenous IL-1 inhibited DNA synthesis in hamster trachea epithelial cells and reproduced the pathology of TCT in hamster tracheal organ culture. Tumor necrosis factor alpha and IL-6, cytokines also associated with inflammation, were unable to reproduce TCT cytopathology. Furthermore, exposure of respiratory epithelial cells to TCT stimulated production of cell-associated IL-1 alpha, which could be detected within 2 h of TCT treatment. In contrast, there was no evidence of TCT-triggered release of IL-1. Previous studies have suggested that intracellular IL-1 alpha, as well as exogenous IL-1 alpha and IL-1 beta, can inhibit cell proliferation. Our results therefore implicate IL-1 alpha, produced by epithelial cells in response to TCT, as a potential intracellular mediator of the primary respiratory cytopathology of pertussis.

Animals↗

IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1,25 dihydroxyvitamin D3.

IL-1-induced osteoblast IL-6 production represents one possible mechanism by which IL-1 augments bone resorption. In this report, we show that the murine osteoblastic cell line (MC3T3-E1) expresses type 1 IL-1 receptors based on 125I-HrIL1 alpha binding, blocked by type 1 IL-1R antibodies (35F5), and analysis of MC3T3 RNA by reverse transcription (RT)-DNA amplification and Northern analysis. MC3T3 cells do not express detectable type 2 IL-1R mRNA by RT-DNA amplification. IL-1 induces (IL-1 ED50, 0.1 pM) IL-6 production through the type 1 IL-1R as 35F5 antibodies block IL-1-stimulated IL-6 production. Vitamin D3 increases IL-1R expression dose- and metabolite-dependently, with 1,25-(OH)2D3 having the greatest potency, and also enhances IL-1's capacity to stimulate IL-6 production at low IL-1 levels. Both IL-1 and 1,25-(OH)2D3 induce type 1 IL-1R and not type 2 IL-1R upregulation based on ligand binding and RT-DNA amplification. Increased IL-1R expression requires a 5-7-h treatment and is protein/RNA synthesis dependent. These observations imply that IL-1-induced IL-6 production in osteoblasts is mediated by type 1 IL-1Rs and that increased IL-1R expression could play a role in mediating IL-1-induced skeletal responses.

3T3 Cells↗

Updated care guidelines for patients with automatic implantable cardioverter defibrillators.

Since its clinical introduction, AICD therapy has gained significant acceptance. Some physicians consider it the "gold standard" in treating malignant tachyarrhythmias associated with sudden cardiac death. As the technology and therapy application have grown, nursing responsibilities have evolved as well. And, with the forthcoming combinations of technology such as AICDs with antitachycardia pacing and bradycardia pacing, the sophistication of the therapy is expected to increase. However, the most critical role for nurses in AICD patient care remains education. Increased utilization has made AICD implants more common, but many patients still lack the initial information and acceptance needed for therapeutic success. Health-care professionals who continue to update and share their understanding of this life-saving technology make invaluable contributions to the care of these patients who have received a second chance at life.

Defibrillators, Implantable↗

Sensing aberration by the automatic implantable cardioverter defibrillator during intraoperative testing.

A 50-year-old man underwent replacement of his automatic implantable cardioverter defibrillator (AICD) because a magnet test revealed severe battery depletion. He had had his unit implanted 18 months previously after an episode of sudden cardiac death. He had documented torsades de pointes and inducible ventricular tachycardia, confirmed by electrophysiologic study. Before a new unit was implanted thresholds were measured by an external cardioverter defibrillator. Ventricular fibrillation (VF) was induced by alternating current through a standard, line-operated battery charger with stimulation delivered to the epicardium via rate-sensing electrodes. VF was allowed to continue for 10 seconds before shock was delivered. Termination of VF required 15 joules, which was higher than that required at initial implantation 18 months earlier. The new pulse generator was activated for testing and VF was again induced. The AICD discharged after 12.3 seconds. Prior to wound closing, the AICD was deactivated by magnet. Instead of R-wave synchronous beeping tones during deactivation, double beeping tones were heard. Electrogram recordings revealed abnormalities of the T-wave and ST segment of the rate-sensing electrodes, which were the cause of the tone irregularities. Stabilization of the T-wave and ST segment occurred within 8 minutes and the tones became normal. The procedure was then completed.

Electric Countershock↗