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Biomedical subjects

Daniel A Culver

Publications and source records attributed to Daniel A Culver.

12 recordsLinked to original sources
PubMed2005

Suppression of activin A in autoimmune lung disease associated with anti-GM-CSF.

Pulmonary alveolar proteinosis (PAP) is an autoimmune disorder characterized by neutralizing autoantibodies to granulocyte-macrophage colony stimulating factor (GM-CSF). Surfactant metabolism is severely dysregulated in PAP, resulting in a foam cell appearance of alveolar macrophages. Microarray analysis of RNA from PAP bronchoalveolar lavage (BAL) cells to explore autoimmune-related genes yielded evidence of a deficiency of activin A, a cytokine implicated in regulation of B-cell proliferation and reduction of foam cell formation. Subsequent studies confirmed a severe deficiency of activin A gene expression and protein secretion in PAP BAL cells and marked reduction of activin A protein in PAP BAL fluids compared to healthy controls. PAP cells, however, like those of healthy controls, were capable of elevated activin A production in response to GM-CSF. Treatment with activin A in vitro suppressed proliferation of PAP peripheral blood B-cells in a receptor-dependent manner and also reduced secretion of anti-GM-CSF autoantibody. These studies are the first to suggest that activin A may play a role in autoimmune disease.

Activins↗
PubMed2005

Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.

Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo.

Adult↗
PubMed2005

Discordant utility of ideal body weight and body mass index as predictors of mortality in lung transplant recipients.

BACKGROUND: An upper limit of 130% predicted ideal body weight (PIBW) has been promulgated for assessing lung transplant (LTx) candidacy, but no data in the lung transplant population support this value. A prior study used body mass index (BMI) to suggest greater mortality risk in obese allograft recipients, but the number of studied patients was small. METHODS: Pre-operative PIBW percentage and BMI were obtained for all first-time, adult LTx recipients at our institution (n = 283). We compared survival data at 90 days and as of July 31, 2002, using multivariable regression and Cox modeling. RESULTS: There were 46 obese (BMI > or = 30) patients and 72 patients >130% PIBW, including 43 patients previously thought to fall within a normal PIBW range who were reclassified as overweight for this analysis. Cox modeling revealed no significant impact of PIBW (>130% or continuous) or BMI (>30 kg/m(2) or continuous) on overall survival. Predicted ideal body weight also had no influence on 90-day mortality. When we tested PIBW in the group previously deemed of acceptable weight, we likewise found no association with mortality at 90 days or overall. For BMI only, 90-day odds ratios for death were significantly greater for obese (BMI > or = 30; odds ratio, 3.16; 95% confidence interval, 1.05-9.48) patients than for normal-weight patients. CONCLUSION: Indices of pre-operative obesity did not predict long-term outcome in this large cohort of LTx recipients. The data suggest that BMI stratification may identify a group of patients at risk for increased short-term mortality, whereas PIBW is not a significant outcome predictor.

Adolescent↗
PubMed2005

Auto-positive end-expiratory pressure: mechanisms and treatment.

Auto-positive end-expiratory pressure (auto-PEEP) is a common problem in patients receiving full or partial ventilatory support, as well as in those ready to be weaned from the ventilator. Physicians should be alert for it and take measures to reduce it, as it can have serious consequences.

Humans↗
PubMed2004

Reprocessing the bronchoscope: the challenges.

Spread of infection through the flexible bronchoscope is underrecognized and underreported. Prevention of bronchoscopy-induced infection requires increased vigilance by the physician, assiduous implementation of reprocessing protocols, and closer collaboration between bronchoscopy personnel, infection control practitioners, and instrument manufacturers. Patient safety depends on adequate disinfection of bronchoscopes and accessories used, as well as proper training of bronchoscopists, nurses, and ancillary staff. It is important to recognize that microbial transmission may occur via any part of instruments or anything in contact with the instruments including cleaning solutions, automated washers, and rinsing water. Numerous surveys have suggested poor adherence to published preventive guidelines. To address the challenges of reprocessing bronchoscopes, all users must comply with guidelines for cleaning and disinfection and each procedure should be performed with a clean, disinfected bronchoscope.

Journal Article↗
PubMed2004

Pulmonary sarcoidosis: new genetic clues and ongoing treatment controversies.

The wide-ranging, multisystemic manifestations of sarcoidosis can make diagnosis and management difficult. Corticosteroid treatment is effective, but the optimal time to start, the dose, and the duration of treatment are controversial. We are just beginning to understand the genetic basis of sarcoidosis.

Adrenal Cortex Hormones↗
PubMed2003

Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis.

The ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR gamma), has pleiotropic effects on lipid and glucose metabolism as well as modulating immune activity. In Th1-predominant models of inflammatory bowel disease and arthritis, PPAR gamma ligands can ameliorate clinical disease severity, partly by downregulating a range of inflammatory cytokines. However, PPAR gamma has not been evaluated in chronic sarcoidosis, a disease characterized by persistent activation of Th1 immune responses in alveolar macrophages. We hypothesized that a deficiency of PPAR gamma activity contributes to ongoing inflammation in pulmonary sarcoidosis via failure to repress proinflammatory transcription factors. To address this, we studied eight patients with active sarcoidosis and nine healthy control subjects by bronchoscopy. Bronchoalveolar lavage specimens from patients revealed a striking reduction of PPAR gamma activity by electrophoretic mobility shift assay in alveolar macrophages compared with healthy control subjects, with a concomitant upregulation of nuclear factor (NF)-kappa B activity. Immunostaining and real-time polymerase chain reaction demonstrated reductions of PPAR gamma nuclear protein and gene expression. The data show for the first time that alveolar macrophages from patients with active sarcoidosis exhibit activation of NF-kappa B and deficiency of PPAR gamma. Although these results do not demonstrate a direct causal effect, they are consistent with the hypothesis that insufficient PPAR gamma activity contributes to ongoing dysregulated inflammation in pulmonary sarcoidosis by failing to suppress NF-kappa B.

Base Sequence↗
PubMed2002

Arterial infection and staphylococcus aureus bacteremia after transfemoral cannulation for percutaneous carotid angioplasty and stenting.

In this report, we present a patient who developed an infected femoral artery after repuncture cannulation for carotid angioplasty and intraluminal stenting. The case was complicated by persistent bacteremia and a delay in diagnosis before it was managed successfully with an autogenous replacement graft and appropriate antibiotics. Overt stent infection is exceedingly rare, but according to the literature describing transfemoral coronary artery intervention, the spectrum of clinical syndromes related to infection of the arterial puncture site includes local invasion, pseudoaneurysm formation, septic embolization to the distal limb, and bacteremia. The diagnosis requires a high degree of clinical suspicion and is often delayed. Although the incidence of infectious complications reported for percutaneous intra-arterial interventions historically has been low, the absolute number of these complications almost certainly will increase in the future because of the expanding array of interventional procedures that is becoming available.

Aged↗
PubMed2002

Syndrome of iron pill aspiration.

Bronchial stenosis (BS) consequent to iron pill aspiration (IPA) has been observed in few reported cases. This condition is often irreversible and may necessitate lobectomy in severe cases. Unlike most foreign bodies (FBs), the iron pill disintegrates in the airway and cannot be detected on bronchoscopy. However, bronchial biopsy and lung tissue may reveal iron deposits along with airway inflammation months after the aspiration. Thus, IPA can be diagnosed by a triad of aspiration, airway inflammation, and iron deposits on histology even in the absence of an FB. We report a case of IPA with BS in which the diagnosis was established by bronchial biopsy and was successfully managed with balloon bronchoplasty and therapy with topical mitomycin C.

Aged↗
PubMedDate not supplied

Transudative chylothorax: report of two cases and review of the literature.

Transudative chylothorax is a rare entity that has been associated with a limited range of clinical settings. To date, transudative chylothoraces have been described in only 13 patients, most commonly as a result of hepatic cirrhosis. Recognition of the transudative nature of these effusions is important to avoid unnecessary diagnostic testing and inappropriate management strategies. This report describes the presentation, diagnosis and management of two patients with transudative chylothoraces, and provides a brief review of the relevant literature.

Ascites↗