Biomedical subjects

David R Park

Publications and source records attributed to David R Park.

5 recordsLinked to original sources

PubMed2006

cDNA microarray analysis reveals fundamental differences in the expression profiles of primary human monocytes, monocyte-derived macrophages, and alveolar macrophages.

We report the systematic use of large-scale cDNA microarrays to study the gene expression profiles of primary human peripheral blood monocytes (MONO) in comparison with in vitro-differentiated, M-CSF-induced MONO-derived macrophages (MAC) and primary human alveolar MAC (AM), obtained by bronchoalveolar lavage from the lungs of normal volunteers. These studies revealed large-scale differences in the gene expression profile between both MAC types (MAC and AM) and MONO. In addition, large differences were observed in the gene expression profiles of the two MAC types. Specifically, 21% of genes on the array (2904 out of 13,582) were differentially expressed between AM and MONO, and 2229 out of 13,583 probes were differentially expressed between MAC and AM. Our expression data show remarkable differences in gene expression between different MAC subpopulations and emphasize the heterogeneity of different MAC populations. This study underscores the need to scrutinize models of MAC biology for relevance to specific disease processes.

Adult↗

PubMed2005

The microbiology of ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a common complication of ventilatory support for patients with acute respiratory failure and is associated with increased morbidity, mortality, and costs. Awareness of the microbiology of VAP is essential for selecting optimal antibiotic therapy and improving these outcomes. The specific microbial causes of VAP are many and varied. Most cases of VAP are caused by bacterial pathogens that normally colonize the oropharynx and gut, or that are acquired via transmission by health-care workers from environmental surfaces or from other patients. Common pathogens include Pseudomonas species and other highly resistant Gram-negative bacilli, staphylococci, the Enterobacteriaceae, streptococci, and Haemophilus species. Antibiotic-resistant pathogens such as Pseudomonas and Acinetobacter species and methicillin-resistant strains of Staphylococcus aureus are much more common after prior antibiotic treatment or prolonged hospitalization or mechanical ventilation, and when other risk factors are present. The bacterial pathogens responsible for VAP also vary depending on patient characteristics and in certain clinical circumstances, such as in acute respiratory distress syndrome or following tracheostomy, traumatic injuries, or burns. But these differences appear to be due primarily to the duration of mechanical ventilation and/or degree of prior antibiotic exposure of these patients. The causes of VAP can vary considerably by geographic location (even between units in the same hospital), emphasizing the importance of local epidemiological and microbiological data. Atypical bacteria, viruses, and fungi also have been implicated as causes of VAP, but these pathogens have not been studied systematically and their role is presently unclear. In conclusion, information about the microbiology of VAP serves to guide optimal antibiotic therapy. The risk of antibiotic-resistant pathogens can be estimated using simple clinical features and awareness of local microbiology patterns. The roles of atypical bacterial and nonbacterial pathogens in VAP are incompletely understood and should be investigated further.

Anti-Bacterial Agents↗

PubMed2005

Antimicrobial treatment of ventilator-associated pneumonia.

Ventilator-associated pneumonia is a common complication of ventilatory support for patients with acute respiratory failure and is associated with increased morbidity, mortality, and costs. Optimal antimicrobial therapy is an essential part of successful management of ventilator-associated pneumonia. Numerous safe and effective antimicrobial drugs are available, and their efficacy can be optimized by attention to basic pharmacokinetic and pharmacodynamic principles. An adequate initial empiric antimicrobial regimen is essential, because inadequate initial therapy is consistently associated with increased mortality. This regimen must be selected before final microbiology results become known, but likely pathogens and antimicrobial resistance patterns can be predicted based on published guidelines, patient-specific factors, and local epidemiologic data. Nevertheless, the initial regimen must often be broad-spectrum and typically requires combination therapy, with 2 or 3 different drugs, if there are risk factors for multidrug-resistant pathogens. The antimicrobial regimen can be narrowed or discontinued as culture and susceptibility results permit. This de-escalation strategy ensures adequate initial antimicrobial therapy for most patients but lessens unnecessary antimicrobial exposure. The best diagnostic approach used to guide therapy, the optimum duration of therapy, and the roles of combination therapy, rotating therapy, and unconventional approaches to antimicrobial therapy all remain uncertain.

Anti-Bacterial Agents↗

PubMed2003

Fas (CD95) induces proinflammatory cytokine responses by human monocytes and monocyte-derived macrophages.

Fas (CD95, APO-1) is regarded as the prototypical cell death receptor of the TNFR superfamily. Fas-induced apoptosis is generally considered to be a noninflammatory process, contributing to the silent resolution of immune and inflammatory responses. However, accumulating evidence indicates that Fas may also induce cellular activation signals. We hypothesized that Fas could activate proinflammatory cytokine responses by normal human monocytes and macrophages. Monocytes were isolated by negative immunoselection from the PBMC fraction of venous blood from healthy volunteers, and monocyte-derived macrophages were cultivated in vitro. Both monocytes and monocyte-derived macrophages released TNF-alpha and IL-8 following Fas ligation, and conditioned medium from Fas-activated monocytes and macrophages induced the directed migration of neutrophils in a chemotaxis assay. Fas-induced monocyte cytokine responses were associated with monocyte apoptosis, nuclear translocation of NF-kappaB, and cytokine gene expression and were blocked by caspase inhibition but not by inhibition of IL-1beta signaling. In contrast, Fas-induced macrophage cytokine responses occurred in the absence of apoptosis and were caspase independent, indicating maturation-dependent differences in the Fas signaling pathways that lead to proinflammatory cytokine induction. Rather than contributing to the resolution of inflammation, Fas ligation on circulating monocytes and tissue macrophages may induce proinflammatory cytokine responses that can initiate acute inflammatory responses and tissue injury.

Apoptosis↗

PubMed2003

Cost and incidence of social comorbidities in low-risk patients with community-acquired pneumonia admitted to a public hospital.

CONTEXT: There are up to 1 million patients treated in acute-care hospitals for community-acquired pneumonia (CAP), with an estimated annual cost > 8 billion dollars. A newly validated CAP outcomes prediction rule developed by Fine and colleagues has been advocated as a guide to hospitalization decisions. OBJECTIVE: To evaluate the clinical characteristics, costs of care, and resource utilization of patients with low-risk CAP at an urban public hospital serving an indigent population. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study from June 1, 1994 to May 31, 1996. MAIN OUTCOME MEASURES: Clinical characteristics and costs of care of patients with low-risk CAP and features associated with low-risk CAP in this population. RESULTS: A total of 522 patients were identified at the time of hospital admission as having CAP; 97 patients (19%) were HIV positive on hospital admission and excluded. Of the remaining 425 patients, 253 patients (60%) were classified as pneumonia severity index (PSI) class I-III (low risk). Of the patients with low-risk CAP, only four patients (1.6%; 95% confidence interval, 0.4 to 4.0%) died during hospitalization. Low-risk CAP was both costly and accounted for significant resource use (35.4% of total CAP costs, and 45% of all CAP bed days). Of the patients with low-risk CAP, there were 138 patients (55%) who could potentially have been treated as outpatients (absence of altered mental status, hypotension, hypoxia on hospital admission, or direct ICU admission). However, 49% of these patients had a history of alcoholism, 20% had a blood alcohol level > 50 mg/dL, and 44% were homeless. CONCLUSIONS: A significant proportion of the patients admitted with CAP to a public hospital had low-risk CAP and accounted for a significant proportion of the CAP bed days and costs. The use of the PSI accurately predicted which patients would be at low risk for death; however, the utility of using the PSI to reduce low-risk CAP hospital admissions would have been of limited benefit. High rates of homelessness, substance abuse, and medical needs not captured in the PSI would preclude many of these patients from unsupervised outpatient treatment.

Adolescent↗