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Biomedical subjects

W Chamberlin

Publications and source records attributed to W Chamberlin.

13 recordsLinked to original sources

Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury.

Neutrophil (PMN) functions, such as production of toxic oxygen (O2) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis. We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs. We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H2O2) production by zymosan-activated PMN. We examined the mixed venous to arterial difference in H2O2(delta H2O2) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization. Septic patients had higher mixed venous H2O2/10(6) PMN, whereas lung injury patients had higher arterial H2O2/10(6) PMN. The control group had the same H2O2/10(6) PMN in mixed venous and arterial blood. The delta H2O2 in septic, lung injury, and control groups were 0.35 +/- 0.22, -0.31 +/- 0.48, and -0.01 +/- 0.04 nmol H2O2/10(6) PMN, respectively. The mixed venous to arterial H2O2 gradient distinguished septic patients from the control and lung injury patients (p less than 0.05). Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery. Alternatively, neutrophil-endothelial interactions may downregulate toxic O2 metabolite production by PMN during their transit through microvascular beds.

Adult

Effect of sodium azide on hydrogen peroxide production by zymosan-activated human neutrophils.

Stimulated neutrophils (PMNs) produce large quantities of superoxide anion, which is the precursor for hydrogen peroxide (H2O2). We developed a new fluorimetric assay to measure the H2O2 released by zymosan A-activated PMNs utilizing the oxidation of p-hydroxyphenylacetic acid by H2O2 to its fluorescent dimer in the presence of horseradish peroxidase. Zymosan-activated PMNs isolated from nine healthy volunteers and 20 patients with acute hypoxemic respiratory failure (AHRF) released after 90 min 2.3 +/- 0.3 and 2.4 +/- 1.3 nmol H2O2/10(6) PMNs, respectively. Inhibition of the heme enzymes by 1.0 mM sodium azide (NaN3) increased the H2O2 production to 21.6 +/- 4.4 nmol H2O2/10(6) PMNs in the control group (P less than 0.001), and to 22.5 +/- 14.7 nmol H2O2/10(6) PMNs in patients with AHRF (P less than 0.001). Incubation temperature, room temperature or 37 degrees C, did not change the total amount of H2O2 produced after 90 min by zymosan-activated PMN. Addition of NaN3 improved both the sensitivity and reproducibility of the measurement of H2O2 and allowed detection of H2O2 released by PMNs with coefficients of variation of less than 5% at PMN concentrations as low as 0.1 x 10(6) cells/ml. The amount of H2O2 released by activated PMNs did not distinguish healthy controls from patients with AHRF.

Adult

The epidemiology of Pseudomonas aeruginosa in oncology patients in a general hospital.

Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.

Female

Occult aminoglycoside resistance in Pseudomonas aeruginosa: epidemiology and implications for therapy and control.

The epidemiology of aminoglycoside-resistant Pseudomonas aeruginosa was evaluated in an intensive care unit (ICU) with serial surveillance cultures of throat and rectum. Bacterial population analysis performed by replica plating of primary isolation plates onto gentamicin-containing agar revealed the presence of resistant subpopulations in the initial isolates from 41 (71%) of 58 consecutive assessable patients; these isolates were stably resistant and proportionately less susceptible to other aminoglycosides. An increase in resistant subpopulations occurred during the ICU stay in 34% of 38 colonized patients cultured serially as opposed to none of 23 followed after ICU discharge (P = .0008). Isolates of P. aeruginosa from patients who received aminoglycosides in the ICU were more likely to show an increase in resistance than were isolates from other patients (55% vs. 11%; P = .005); decreasing resistance after ICU discharge followed discontinuation of antibiotic administration. ICU mortality was higher in patients with increasingly resistant subpopulations (69% vs. 16%; P = .0004). The difficulty in treating infections with P. aeruginosa and in controlling drug resistance likely relates to the common carriage of clinically undetected resistant subpopulations that emerge during therapy.

Aminoglycosides

Antibiotic-resistant flora in nursing home patients admitted to the hospital.

To study carriage of multiply resistant gram-negative bacilli, 50 patients admitted to the hospital from nursing homes (NHs) and 50 control admissions not from NHs were matched for age and recent antibiotic use. Their antibiotic resistance patterns were similar: 20 NH patients and 14 controls had resistant strains. However, significantly more patients (64%) from NHs with large numbers of "skilled beds" had resistant bacteria than did patients from small NHs (21%) or controls (28%). Also, more patients from NHs had members of the Proteus-Providencia-Morganella group in their urine than did controls. Discriminant analysis showed that residence in NHs with large numbers of skilled beds, recent antibiotic use, and bladder dysfunction (indwelling catheter or incontinence) were independently important in predicting carriage of resistant strains in NH and control patients. Over 75% of resistant isolates were from rectal specimens, emphasizing the occult way that such strains are brought into the hospital.

Aged

Epidemiology of endemic Pseudomonas aeruginosa: why infection control efforts have failed.

The epidemiology of Pseudomonas aeruginosa was evaluated in an intensive care unit for a period of six months by means of serial surveillance and environmental cultures. One hundred (37%) of 270 patients were noted to be colonized: 63 at the time of their admission and 37 during their stay on the unit. Colonization at the time of admission was associated with length of hospitalization before admission to the intensive care unit, age, gastrointestinal disease, and prior use of antibiotics. The strains acquired on the intensive care unit represented several different serotypes, with little clustering; the source of most strains was not found. In only 12 cases did the acquisition of P. aeruginosa appear to represent cross-infection; the use of barrier isolation could have prevented at most five of these cases. Undetected endogenous gastrointestinal carriage may have been responsible for many other apparent acquisitions. Clinical infection in association with preceding gastrointestinal colonization developed in 20 patients. The data indicate that traditional control measures aimed at the prevention of exogenous acquisition of P. aeruginosa are unlikely to have an impact on the overall incidence of infection and that efforts to prevent infection in patients who are already colonized are necessary.

Communicable Disease Control

Effects of radiation on hematopoietic stroma.

The effects of x-irradiation on the CFU-S and on the hematopoietic stroma (HS-P) were studied and compared. Exposure to 300 rad reduced the CFU-S population to less than 1% of normal; by contrast more than 500 rad was required to detectably damage the HS-P. Although exposture to 500 rad did not detectably affect HS-P function, a second exposure to 500 rad as much as 4 weeks later did appreciably affect the HS-P. In addition, whereas the CFU-S returned to the pre-irradiation level within 6 weeks, the HS-P did not significantly recover. From these data we conclude that, with respect to the initial impact and exposure dose, HS-P is more radioresistant than CFU-S, but recovery from radiation induced damage of HS-P occurs slowly or does not take place.

Animals