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Thomas A Neff

Publications and source records attributed to Thomas A Neff.

22 records · Page 2Linked to original sources

Long-term assessment of lung function in survivors of severe ARDS.

STUDY OBJECTIVES: To investigate the long-term outcome of lung function in survivors of severe ARDS after modern treatment strategies including lung protective mechanical ventilation and prone positioning maneuvers. DESIGN: Follow-up cohort study. SETTING: University hospital pulmonary division and level 1 trauma center. PATIENTS: Sixteen survivors of severe ARDS (from 1992 to 1994) with a lung injury score > or = 2.5. MEASUREMENTS: The follow-up study (from 1995 to 1996) included interview, physical examination, chest radiographs, static and dynamic lung volumes, diffusion capacity of the lung for carbon monoxide (DLCO), blood gas analysis, and cardiopulmonary exercise testing (CPET). RESULTS: The mean +/- SD interval between hospital discharge and functional assessment was 29.5 +/- 8.7 months (range, 15.0 to 40.7 months). In approximately one half of the patients, mild abnormalities in static and dynamic lung volumes were found. In 25% (4 of 16 patients), lung function was obstructive; in 25% (4 of 16 patients), lung function was restrictive; and in 6.3% (1 of 16 patients), a combined obstructive-restrictive pattern was revealed. DLCO was impaired in 12.5% (2 of 16 patients); gas exchange during exercise was impaired in 45.5% (5 of 11 patients). CONCLUSIONS: Residual obstructive and restrictive defects as well as impaired pulmonary gas exchange remain common after severe ARDS. CPET is a very sensitive measure to evaluate residual impairment of lung function after ARDS. Using CPET, reduced pulmonary gas exchange can be detected in many patients with normal DLCO.

Adult↗

The Panomat P-10 micro-volumetric infusion pump is suitable for continuous drug administration at minimal flow rates.

PURPOSE: To evaluate the performance of the Panomat P-10 micro-volumetric infusion pump for its use in drug administration at minimal flow rates (microL x hr(-1); e.g., intrathecal application). METHODS: Fluid delivery at steady state conditions, and after vertical displacement of the syringe pump by -50 cm was determined gravimetrically. The Panomat P-10 infusion pump was evaluated at 4, 10, 20, 50 and 100 microL x hr(-1), and compared to a conventional syringe pump assembly at 100, 200, 500 and 1000 microL x hr(-1). Measurements were repeated twice with two different devices of each syringe pump system, and with two syringes. Data are reported as mean +/- SD. RESULTS: Steady state fluid delivery of the Panomat P-10 infusion pump revealed less than 5% deviation to set flow rate at 10, 20, 50 and 100 microL x hr(-1), and 12% deviation at 4 microL x hr(-1). Mean zero-drug delivery time (ZDDT) after lowering the pump by 50 cm at 4 microL x hr(-1) flow rate was 38.4 +/- 7.3 min. At 100 microL x hr(-1) and with original infusion line ZDDT was almost 20 times shorter when compared to the conventional syringe pump assembly (1.5 +/- 0.5 min vs 28.5 +/- 5.0 min). CONCLUSION: The tested Panomat P-10 micro-volumetric pump shows an acceptable flow accuracy as well as a low susceptibility to vertical displacement, and is therefore suitable for continuous drug administration at minimal flow rates. The technology used in this pump carries potential implications for a new generation of syringe pumps.

Drug Delivery Systems↗

Protection of innate immunity by C5aR antagonist in septic mice.

Innate immune functions are known to be compromised during sepsis, often with lethal consequences. There is also evidence in rats that sepsis is associated with excessive complement activation and generation of the potent anaphylatoxin C5a. In the presence of a cyclic peptide antagonist (C5aRa) to the C5a receptor (C5aR), the binding of murine 125I-C5a to murine neutrophils was reduced, the in vitro chemotactic responses of mouse neutrophils to mouse C5a were markedly diminished, the acquired defect in hydrogen peroxide (H2O2) production of C5a-exposed neutrophils was reversed, and the lung permeability index (extravascular leakage of albumin) in mice after intrapulmonary deposition of IgG immune complexes was markedly diminished. Mice that developed sepsis after cecal ligation/puncture (CLP) and were treated with C5aRa had greatly improved survival rates. These data suggest that C5aRa interferes with neutrophil responses to C5a, preventing C5a-induced compromise of innate immunity during sepsis, with greatly improved survival rates after CLP.

Animals↗

Increased C5a receptor expression in sepsis.

Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.

Animals↗