PubMed Health⌕ Search

Biomedical subjects

L McCaig

Publications and source records attributed to L McCaig.

16 recordsLinked to original sources
PubMed2001

Effects of alveolar surfactant aggregates on T-lymphocyte proliferation.

The effects of alveolar large aggregate (LA) and small aggregate (SA) surfactant subfractions isolated from healthy adult rats on mitogen-stimulated proliferative responses of human peripheral blood mononuclear cells (PBMC) was examined. Various concentrations of total surfactant suppressed proliferation of stimulated lymphocytes by up to 95% of mitogen-stimulated cells alone. LA subfractions of total surfactant had no effect on proliferation, whereas SA significantly enhanced the lymphocyte proliferation at lower concentrations (7.8 microg/ml) compared to mitogen-stimulated cells alone. Higher concentrations of SA (62.5 microg/ml) inhibited lymphocyte proliferation. This concentration-dependent effect of SA on proliferation of PBMC was also present when cells were stimulated with various lectins including anti-CD3, concanavalin A and phytohemagglutinin. Analysis of the supernatant of mitogen-stimulated cell cultures treated with inhibitory concentrations of SA showed decreased amounts of interleukin (IL)-2, compared to cells alone, which could be reversed by adding exogenous IL-2 to the cell cultures with the SA. These results suggest that alveolar surfactant subfractions have distinct functions within the alveoli, both biophysically and with respect to their effects on the host's immunomodulatory responses.

Animals↗
PubMed2001

Mechanical ventilation of isolated septic rat lungs: effects on surfactant and inflammatory cytokines.

The effects of mechanical ventilation (MV) on the surfactant system and cytokine secretion were studied in isolated septic rat lungs. At 23 h after sham surgery or induction of sepsis by cecal ligation and perforation (CLP), lungs were excised and randomized to one of three groups: 1) a nonventilated group, 2) a group subjected to 1 h of noninjurious MV (tidal volume = 10 ml/kg, positive end-expiratory pressure = 3 cmH(2)O), or 3) a group subjected to 1 h of injurious MV (tidal volume = 20 ml/kg, positive end-expiratory pressure = 0 cmH(2)O). Nonventilated sham and CLP lungs had similar compliance, normal lung morphology, surfactant, and cytokine concentrations. Injurious ventilation decreased compliance, altered surfactant, increased cytokines, and induced morphological changes compared with nonventilation in sham and CLP lungs. In these lungs, the surfactant system was similar in sham and CLP lungs; however, tumor necrosis factor-alpha and interleukin-6 levels were significantly higher in CLP lungs. We conclude that injurious ventilation altered surfactant independent of sepsis and that the CLP lungs were predisposed to the secretion of larger amounts of cytokines because of ventilation.

Animals↗
PubMed2001

Effects of mechanical ventilation of isolated mouse lungs on surfactant and inflammatory cytokines.

Mechanical ventilation of the lung is an essential but potentially harmful therapeutic intervention for patients with acute respiratory distress syndrome. The objective of the current study was to establish and characterize an isolated mouse lung model to study the harmful effects of mechanical ventilation. Lungs were isolated from BalbC mice and randomized to either a nonventilated group, a conventionally ventilated group (tidal volume 7 mL x kg(-1), 4 cm positive endexpiratory pressure (PEEP)) or an injuriously ventilated group (20 mL x kg(-1), 0 cm PEEP). Lungs were subsequently analysed for lung compliance, morphology, surfactant composition and inflammatory cytokines. Injurious ventilation resulted in significant lung dysfunction, which was associated with a significant increase in pulmonary surfactant, and surfactant small aggregates compared to the other two groups. Injurious ventilation also led to a significantly increased concentration of interleukin-6 and tumour necrosis factor-a in the lavage. It was concluded that the injurious effects of mechanical ventilation can effectively be studied in isolated mouse lung, which offers the potential of studying genetically altered animals. It was also concluded that in this model, the lung injury is, in part, mediated by the surfactant system and the release of inflammatory mediators.

Animals↗
PubMed1999

Dosing and delivery of a recombinant surfactant in lung-injured adult sheep.

The purpose of this study was to evaluate a surfactant based on a recombinant surfactant protein-C (rSP-C) at three different doses (25, 100, and 200 mg lipid/kg) in the saline lavage adult sheep model of acute lung injury. All three doses resulted in significant improvements in gas exchange, although the 100 and 200 mg/kg doses were superior to the 25 mg/kg dose. There were no significant differences in effect of the 100 and 200 mg/kg doses. In addition, the physiologic efficacy and lobar surfactant distribution patterns were similar when two different surfactant delivery methods were compared. This comparison involved administering the surfactant directly into each lobe under bronchoscopic guidance, versus instilling the surfactant through an endotracheal tube into the lungs. However, the former technique took significantly longer to perform (24.5 +/- 3.3 min versus 11.6 +/- 2.5 min, p < 0.05) and required a skilled bronchoscopist. In conclusion, rSP-C surfactant was effective in improving gas exchange in this model of lung injury, although higher doses were required for optimal responses. The bronchoscopic administration technique produced results similar to those of the tracheal instillation method, but had some disadvantages that may limit the widespread clinical use of this technique in patients with lung injury.

Animals↗
PubMed1998

Characterizing alterations in the pulmonary surfactant system in a rat model of Pseudomonas aeruginosa pneumonia.

Bacterial pneumonia remains a significant cause of patient morbidity and mortality worldwide. Pulmonary surfactant serves to maintain homeostasis in the lung through the maintenance of alveolar stability and the regulation of the alveolar immune response. The purpose of this study was to characterize the lung injury and associated surfactant alterations in a rat model of acute Pseudomonas aeruginosa pneumonia. Pneumonia was induced in male Sprague-Dawley rats via intratracheal injection of 0.2 ml, phosphate-buffered saline (PBS) containing P. aeruginosa (6x10(8) colony-forming units x mL(-1)). Control animals received 0.2 mL sterile PBS. Twenty-four hours after inoculation, the pneumonia group (PN) exhibited clinical signs of pneumonia including deficits in gas exchange, leukopenia and elevated arterial lactate levels. Morphological assessment confirmed the presence of pneumonia with airspaces filled with polymorphonuclear cells. Lung homogenate analysis demonstrated evidence of bacterial colonization of pneumonic lung tissue. Lung compliance was also significantly lower in the PN group. Lung lavage analysis of PN rats revealed the pooled surfactant levels to be lower and the surfactant function reduced compared to control rats. Surfactant composition was also found to be altered in PN rats. These results demonstrate that in Pseudomonas aeruginosa pneumonia, the pulmonary surfactant system is both poorly functioning and reduced in quantity. These alterations may contribute to the lung dysfunction characteristic of this disorder.

Acute Disease↗
PubMed1997

Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and in vitro.

Within the alveolar space pulmonary surfactant is converted from the surface active large aggregates (LA) to the inactive small aggregates (SA). This conversion is affected by a change in surface area, lung injury, breathing pattern, and protease activity. This study examined the effect of N-nitroso-N-methylurethane-induced acute lung injury on aggregate conversion in mechanically ventilated and spontaneously breathing rabbits. Both the in vitro surface area cycling techniques and the in vivo technique of intratracheally injecting radiolabeled LA were used for analyzing aggregate conversion. Mechanical ventilation of injured lungs resulted in increased aggregate conversion and increased surfactant aggregate ratios compared with controls. Spontaneously breathing injured animals had aggregate conversion and aggregate ratios that were not significantly different from controls. In vitro aggregate conversion was slower for LA obtained from injured animals compared with normal animals. We conclude that the mechanical stress of mechanical ventilation results in increased aggregate conversion and aggregate ratios. Furthermore, in vitro conversion of isolated LA does not necessarily reflect the conversion of aggregates within the alveoli.

Animals↗
PubMed1997

Alterations of the endogenous surfactant system in septic adult rats.

Sepsis is the most common factor leading to the acute respiratory distress syndrome (ARDS) and is associated with the highest mortality rate. It has been suggested that the pulmonary surfactant system is altered and contributes to the lung dysfunction associated with ARDS. The objective of this study was to characterize the lung injury, specifically the endogenous surfactant system in septic adult rats. Sepsis was induced in male Sprague-Dawley rats by cecal ligation and perforation and resulted in significant increases in heart rates, respiratory rates, and lactate levels along with positive blood cultures in septic animals compared with a sham control group. Two distinct septic groups were developed, a septic group and a sepsis with lung injury (septic+LI) group. The septic group had no significant differences in oxygenation compared with the sham group, whereas the septic+LI group had significantly lower PaO2 and higher A-a gradient values compared to both the sham and septic groups. The total surfactant pool size was significantly lower in the septic+LI group compared with the sham group. The small surfactant aggregate to large surfactant aggregate ratio was significantly lower in the septic group and was further reduced in the septic+LI group. There were also significantly higher levels of surfactant protein A (SP-A) in both septic and septic+LI groups compared to the sham group. These results demonstrated that the endogenous surfactant system was altered in systemic sepsis without lung dysfunction and is further altered when a lung injury is present.

Analysis of Variance↗
PubMed1996

Emergency department uses of physician assistants and nurse practitioners: a national survey.

A study was undertaken to determine the extent to which physician assistants (PAs) and/or nurse practitioners (NPs) are a source of health care delivery in emergency departments (EDs) in the United States. The National Hospital Ambulatory Medical Survey (NHAMCS) uses a multistage probability sample that examines patient visits within EDs. The sample included 437 hospitals with EDs. Visits were mostly from self-referred patients to EDs within nonfederal, short-stay hospitals, or general hospitals. Analysis of NHAMCS data found that a PA and/or NP was seen for 3.5 million ED visits in 1992. Remarkably little difference in gender, reason for visit, diagnosis, and medication prescribed was found between PA/NP visits and visits to all providers. This was the first study that systematically identified the extent of PA/NP-delivered ED services in the United States and compared it with physician services. Overall, PAs and NPs were found to be significant sources of health care service for hospital EDs. They are involved in care for almost 4% of all ED visits nationally and manage a wider range of conditions than has been previously reported. When types of visits are analyzed, including reasons for ED care, diagnosis, and treatment, it appears that visits associated with care by ED-based PA/NPs are similar to all ED visits, including those attended by emergency medicine physicians. More studies are needed to better understand the role of PAs and/or NPs in various ED settings. Recruitment and use of PAs and NPs may be a cost-effective strategy for improved delivery of emergency services.

Adolescent↗
PubMed1996

Alveolar surfactant aggregate conversion in ventilated normal and injured rabbits.

Alveolar surfactant can be separated into two subtypes; large aggregates and small aggregates. Large aggregates represent the surface active form of surfactant and are the metabolic precursors of small aggregates. Previous studies examined the mechanism by which large aggregates are converted into small aggregates in vitro. We used intratracheal injection of radiolabeled large aggregates in rabbits to probe the aggregate conversion in vivo. After this injection, animals were mechanically ventilated for 60 min. After the animals were killed, the lungs were lavaged, and the percentage of radiolabel present in the small aggregate fraction was determined. Our results showed that ventilation resulted in aggregate conversion and that increases in tidal volume, but not in respiratory rate, correlated with increased conversion. Aggregate conversion in rabbits with acute lung injury correlated significantly with severity of injury. We conclude that a change in surface area (i.e., respiration) is necessary for aggregate conversion in vivo and that the ventilation strategy can affect this conversion. Furthermore, increased aggregate conversion in injured lungs might contribute to increased small-to-large aggregate ratios in these lungs compared with normal lungs.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Timing of exogenous surfactant administration in a rabbit model of acute lung injury.

The purpose of this study was to evaluate early vs. late administration of exogenous surfactant in an adult rabbit model of acute lung injury. Lung injury was induced by repetitive whole lung saline lavage and subsequent mechanical ventilation. Bovine lipid extract surfactant was instilled either 1 (Early) or 4 h (Late) after the last lavage. Animals were monitored for 7 h after the last lavage. Although arterial PO2 values increased significantly immediately after treatment in both the Early and Late groups, this improvement was not sustained in the Late group. There was also a higher incidence of pneumothoraxes in the Late group vs. both the Early group and a nontreated control group. The ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates was higher in the Late group compared with the Early group. Morphological analysis revealed that early surfactant treatment prevented the progression of lung injury over time. We conclude that administration of exogenous surfactant at an early time point in lung injury resulted in superior responses compared with later treatments.

Animals↗
PubMed1994

Altered alveolar surfactant is an early marker of acute lung injury in septic adult sheep.

The purpose of this study was to characterize changes in the endogenous surfactant system in adult sheep rendered septic via cecal ligation and perforation (CLP). Forty-eight hours after CLP, septic animals had significant increases in mean pulmonary artery pressure (PAP) (p < 0.01), cardiac index (CI) (p < 0.01), and arterial lactate (p < 0.05) values compared with their respective baseline values, while the same measurements in a sham-operated control group did not change significantly. The changes in the septic group were associated with significantly lower PaO2 (p < 0.05) and alveolar to arterial (A-a) oxygen gradient values (p < 0.01) at 48 h compared with baseline measurements. No changes in oxygenation occurred within the sham-operated group. Surfactant phospholipid (PL) composition and surface activity measurements of isolated alveolar surfactant aggregate forms were similar for the two groups at 48 h. However, the ratio of poorly functioning small aggregate forms (SA) to superior functioning large aggregates (LA) was significantly increased in the septic versus the sham-operated animals (p < 0.01). This was associated with significantly decreased surfactant protein A (SP-A), B (SP-B), and C (SP-C) levels in septic versus sham-operated animals (p < 0.05). We conclude that sepsis-associated lung injury resulted in altered alveolar surfactant aggregate forms. These changes, together with altered surfactant protein levels, may represent a very sensitive marker of acute lung injury in high-risk patients. Furthermore, these findings suggest that exogenous surfactant given at an early stage of lung injury may mitigate progressive lung dysfunction.

Acute Disease↗
PubMed1993

Aerosolized versus instilled exogenous surfactant in a nonuniform pattern of lung injury.

Previous studies have shown that the underlying patterns of lung injury influence subsequent responses to aerosolized exogenous surfactant. The purpose of this study was to compare aerosolized versus tracheally instilled surfactant in a nonuniform lung injury. Adult sheep underwent whole lung lavage with subsequent HCl instillation into the right middle lobe (RML) and lingula (LING) to create a nonuniform injury. Animals were treated with either nebulized surfactant (Neb.Surf.), tracheally instilled surfactant (Inst.Surf.), or nebulized saline (Neb. Saline). PaO2, alveolar-arterial O2 gradient (PAO2-PaO2), PaCO2, and peak inspiratory pressure (PIP) values all significantly improved during 180 min of continuous aerosolization for Neb.Surf. animals compared with pretreatment values (p < 0.01) and with the other two treatment groups (p < 0.01). Although PaO2 and (PAO2-PaO2) values improved for the Inst.Surf. group by 180 min after treatment (p < 0.05), PaCO2 and PIP values were significantly increased 30 min after surfactant instillation (p < 0.05). Neb. Saline animals had no significant changes in physiologic parameters over 180 min. Approximately 8% of the total aerosolized surfactant deposited in lung tissue was recovered from the more severely damaged RML and LING, compared with approximately 50% of the total instilled surfactant recovered from these lobes. This resulted in significantly greater percentages of the total aerosolized surfactant deposited in each of the remaining lobes compared with the percent deposition of instilled surfactant (p < 0.05). Both the underlying pattern of lung injury and the exogenous surfactant delivery technique may influence clinical responses to surfactant therapy in patients with the adult respiratory distress syndrome (ARDS).

Aerosols↗
PubMed1987

Shedding of oocysts in immunocompetent individuals infected with Cryptosporidium.

In June 1985, we investigated an outbreak of cryptosporidiosis at a day-care center in Florida. Through day-care center-wide stool screening, 33% (28/84) of the children and 22% (4/18) of the staff members submitting stool specimens were found to have cryptosporidiosis. Children 12-35 months of age and their teachers were at highest risk. All but 1 of the Cryptosporidium-positive patients reported diarrhea, which lasted between 1-44 days. Serial stool specimens were obtained from 8 infected individuals (5 children and 3 adults). Duration of oocyst shedding ranged from 8 to more than 50 days and continued in 5 individuals after diarrhea ceased. No relationship was found between duration of oocyst shedding and the age of the patient or duration or severity of diarrhea. Results of the investigation indicate that infected individuals may continue to excrete oocysts and, therefore, may remain infectious for days or weeks after gastrointestinal symptoms disappear.

Adult↗
PubMedDate not supplied

The clinical and laboratory diagnosis of Trichomonas vaginalis infection.

One hundred consecutive female patients attending an inner-city clinic for treatment of sexually transmitted diseases were evaluated for the presence of Trichomonas vaginalis by history, physical examination, 0.85% NaCl wet mount, Papanicolaou smear, and culture. Of the 100 women, 54 were found to be harboring the parasite, as determined by one or more positive diagnostic tests. This prevalence corresponds with that reported previously. The information gained from the history (symptoms and phase of menstrual cycle) and physical examination correlated poorly with results of cultures for T. vaginalis; the organism was isolated more often than symptoms or physical findings would have indicated. Culture was the most sensitive of diagnostic techniques; 48 (89%) of the 54 patients were identified by this method. The Papanicolaou smear detected 35 infections (65%), and the 0.85% NaCl wet mount, 28 (59%). The simplest and most efficient technique for screening women for infection with T. vaginalis may be the Papanicolaou smear, since it is part of the annual physical examination.

Adolescent↗