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P Vacek

Publications and source records attributed to P Vacek.

At least 19 recordsLinked to original sources
PubMed2001

Different accumulation of activated extracellular signal-regulated kinases (ERK 1/2) and role in cell-cycle alterations by epidermal growth factor, hydrogen peroxide, or asbestos in pulmonary epithelial cells.

The extracellular signal-regulated kinase (ERK) pathway is induced by cytokines and oxidative stress. In this study we examined the patterns of localization of phosphorylated ERK proteins in relationship to subsequent phenotypic responses by the mitogenic agent epidermal growth factor (EGF) (5 ng/ ml); hydrogen peroxide (H(2)O(2)) (100 to 300 microM), an inducer of apoptosis; and crocidolite asbestos (5 microg/cm(2) dish) in a nontransformed murine alveolar type II epithelial cell line (C10). Laser scanning cytometry and flow cytometry were used to determine: (1) whether expression of phosphorylated ERKs was cell cycle-related; and (2) whether cell-cycle alterations by agents could be modified after addition of the mitogen-activated protein kinase/ERK kinase (MEK) 1 inhibitor PD98059. In contrast to other stimuli which induced transient increases in phosphorylated ERKs, asbestos caused fiber-associated localization of phosphorylated ERKs that were elevated from 1 to 24 h (P < or = 0.05), and striking apoptosis followed by increased numbers of cells in the S phase at 72 h. In both control and asbestos-exposed cells, the percentage of phosphorylated ERK-positive cells was greatest in cells in the G(2)/M and S phases of the cell cycle. All stimuli caused increased proportions of cells in G(2)/M at 24 h that were inhibited by PD98059 (30 microM). Increases in G(2)/M cells by H(2)O(2) and asbestos also were decreased at 48 h by the MEK1 inhibitor. In addition, PD98059 abrogated elevations in S-phase cells by EGF and H(2)O(2) at 24 h and by asbestos at 72 h. Our results suggest that ERKs mediate cell-cycle alterations during the development of epithelial cell apoptosis or proliferation by diverse ERK stimuli.

Animals↗
PubMed2000

Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro.

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated and/ or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappaB-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are the first to show NF-kappaB-related inflammatory and cytokine gene expression after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity by PM(2.5) in pulmonary epithelial cells.

Air Pollutants↗
PubMed1998

Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells.

Numerous epidemiological studies have demonstrated a positive association between ambient air pollution and adverse health effects including respiratory morbidity, asthma, and lung cancer. It has been suggested in some experimental studies that airborne particulate matter (PM) can produce inflammatory effects, but nothing is known about the possible proliferative and carcinogenic effects of these particles on cells of the lung. We show here that exposure of pulmonary epithelial cells, a cell type affected in acute lung injury, asthma, and lung carcinomas, to nontoxic concentrations of PM in vitro results in increases in c-jun kinase activity, levels of phosphorylated cJun immunoreactive protein, and transcriptional activation of activator protein-1-dependent gene expression. These changes are accompanied by elevations in numbers of cells incorporating 5'-bromodeoxyuridine, a marker of unscheduled DNA synthesis and/or cell proliferation. Data here are the first to demonstrate that interaction of ambient PM with target cells of the lung initiates a cell signaling cascade related causally to aberrant cell proliferation and carcinogenesis.

Air Pollution↗
PubMed1998

Atypical background somatic mutant frequencies at the HPRT locus in children and adults with Down syndrome.

People with Down syndrome are 10-30 fold more likely to develop leukemia than the normal population. To date, little is known regarding the molecular mechanisms underlying this phenomenon. We have previously demonstrated that the spontaneous somatic mutant frequency (Mf) at a reporter gene, hypoxanthine-guanine phosphoribosyl transferase (HPRT), from a normal population showed a strict age dependency with an exponential increase in Mf from birth to late adolescents with a subsequent linear 2-5% increase per year in adults. In this study, we compared HPRT Mf in children and adults with Down syndrome using the HPRT T-cell cloning assay. We determined the Mf at the HPRT locus in 27 subjects with Down syndrome from ages 6 months to 53.4 years. Results demonstrated that background somatic Mf at the HPRT locus in children and adults with Down syndrome are not dependent on age as seen in a normal control population. Results also show that adults with Down syndrome have a significantly lower Mf than normal adults, and that children with Down syndrome have a significantly higher Mf than normal children, although the latter appears to be due to a decreased cloning efficiency (CE). These observations demonstrate that the frequency of spontaneous somatic mutations in children and adults with Down syndrome are atypical compared to normal controls, and suggest that the genetic mechanisms associated with background somatic mutational events in children and adults with Down syndrome may be different.

Adolescent↗
PubMed1998

Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.

Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

Animals↗
PubMed1998

Patterns of c-fos and c-jun proto-oncogene expression, apoptosis, and proliferation in rat pleural mesothelial cells exposed to erionite or asbestos fibers.

Erionite, a naturally occurring fibrous zeolite, is associated with the development of nonmalignant and malignant lung diseases and is more carcinogenic than asbestos fibers in man and rodent inhalation models of disease. To investigate the possible molecular mechanisms of erionite-induced toxicity and carcinogenesis and whether cationic content of erionite fibers was important, we examined c-fos and c-jun mRNA levels, activator protein-1 (AP-1) binding to DNA, and changes in cell proliferation and apoptosis in rat pleural mesothelial (RPM) cells exposed to different cation-substituted erionite fibers or crocidolite asbestos at various concentrations (1, 5, or 10 microg/cm2 dish) at time periods from 8 to 48 h after addition of minerals. c-fos mRNA levels in cells exposed to equal weight concentrations of various erionites and crocidolite fibers were increased comparably. When compared to other fibers, Na-erionite caused significantly increased levels of c-jun mRNA at lower mass concentrations (1 and 5 microg/cm2) than crocidolite asbestos, but comparable AP-1 binding to DNA. In comparison to untreated controls, numbers of RPM cells incorporating 5'-bromodeoxyuridine (BrdU) were increased dramatically after exposure to asbestos or Na-erionite at 5 and 10 microg/cm2. Significant dose-dependent increases in apoptosis were observed with asbestos at all time points, whereas erionites failed to induce apoptosis at 8 or 24 h, with minimal induction at higher concentrations than asbestos at 48 h. These data suggest that erionite increases the balance between cell proliferation (and/or abnormal DNA repair) and apoptosis, a normal mechanism of elimination of transformed or proliferating cells.

Animals↗
PubMed1998

Variations in physicians' judgments about corticosteroid induced osteoporosis by physician specialty.

OBJECTIVE: Longterm corticosteroid use is associated with an increased risk of osteoporosis and fractures. Calcium and vitamin D supplementation and estrogen replacement therapy can decrease this risk, but the majority of patients receiving longterm corticosteroid treatment do not receive treatments to prevent bone loss. We assess whether this is due to variations in physicians' judgments about risks and efficacy of treatments to prevent corticosteroid-induced osteoporosis. METHODS: Questionnaires were mailed to 425 physicians, who were sampled so that half were generalists and half were specialists. Physicians were given hypothetical clinical scenarios involving patients taking corticosteroids and asked to judge the importance of osteoporosis as a risk of corticosteroid treatment, the importance of discussing this side effect with patients, and to indicate how often they would use calcium with vitamin D and estrogen for a hypothetical postmenopausal patient receiving longterm corticosteroid treatment. RESULTS: In total 198 physicians (50%) responded to this survey. Most physicians rated osteoporosis as one of the 3 most significant side effects of corticosteroid treatment for postmenopausal women, but there was significant variation in physician judgments about the importance of corticosteroid induced osteoporosis for premenopausal women (p=0.03) and men (p=0.001). There was also significant variation in physician judgments about the importance of discussing osteoporosis as a side effect with patients (p=0.001), and their use of both calcium and vitamin D (p=0.002) and estrogen replacement therapy (p=0.001) for a hypothetical postmenopausal patient. The physician characteristics most associated with these differences were physician specialty and experience with corticosteroid use. Primary care physicians and physicians who more commonly prescribe corticosteroids were more likely to report that they would use estrogen and calcium to prevent corticosteroid induced bone loss. Physician age, sex, and university affiliation had no association with physician assessments. CONCLUSION: Physicians' judgments varied significantly by physician specialty and experience with corticosteroid use. These data suggest that patients cared for by physicians in different specialties will get varying advice about osteoporosis risk and preventive treatments when receiving longterm corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed1997

Inhibition of protein kinase C prevents asbestos-induced c-fos and c-jun proto-oncogene expression in mesothelial cells.

Asbestos and the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), increase c-fos and c-jun mRNA levels and AP-1 DNA binding activity in rat pleural mesothelial (RPM) cells, a target cell of asbestos-induced mesotheliomas (N. H. Heintz et al., Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Because protein kinase C (PKC) is the intracellular receptor of phorbol ester tumor promoters and asbestos is a putative tumor promoter in the respiratory tract, we hypothesized that PKC might play a critical role in asbestos-induced cell signaling pathways associated with regulation of proto-oncogenes. Using a panel of PKC antibodies, we identified PKC alpha as the major PKC isozyme in RPM cells. We then pretreated cells with phorbol ester dibutyrate to down-modulate PKC or with calphostin C, a specific PKC inhibitor, to determine if depletion of PKC alpha could block asbestos-induced c-fos/c-jun expression. Quantitation of Northern blots showed that fiber-associated c-fos/c-jun mRNA levels were significantly lower either after PKC alpha down-modulation or pretreatment with calphostin C. In addition, to determine whether tyrosine kinases also were involved in proto-oncogene activation by asbestos, tyrphostin AG82 or herbimycin A was added to RPM cells before exposure to asbestos. These inhibitors decreased crocidolite-induced c-fos but not c-jun levels, suggesting that tyrosine kinases have different regulatory roles in asbestos-induced c-fos versus c-jun signaling pathways. The ability to block induction of asbestos-induced proto-oncogene expression using pharmacological intervention may be important in prevention and treatment of asbestos-induced proliferative diseases including lung cancers, mesothelioma, and pulmonary fibrosis.

Animals↗
PubMed1997

Handwashing and glove use in a long-term-care facility.

OBJECTIVES: To determine glove use and handwashing practices, the factors associated with infection control practices, and the frequency of potential microbial transmission in a long-term-care facility (LTCF). DESIGN: Observational study of 230 staff-resident interactions in an LTCF. We recorded resident characteristics, type of activity, staff credentials, and movements of the staff member's hands, then used the LTCF's guidelines to judge appropriateness of glove use and handwashing. SETTING: 255-bed, university-based LTCF in Baltimore, Maryland. PARTICIPANTS: A systematic sample of staff-resident interactions. RESULTS: Gloves were worn in 139 (82%) of 170 interactions when indicated, but changed appropriately in only 1 (16%) of 132. Hands were washed when needed before an interaction in 27%, during an interaction in 0%, and after an interaction in 63%. Gloves were less likely to be used when caring for residents with gastrostomy tubes compared with other residents (relative risk, 0.85; 95% confidence interval, 0.73-0.98). Guidelines were followed more frequently during wound care than during other activities. Microbial transmission potentially could have occurred in 158 (82%) of 193 evaluable interactions. CONCLUSIONS: We documented marked deficiencies in glove and handwashing, demonstrated the possible impact of these deficiencies, and identified factors associated with inadequate handwashing and glove use. This information can be used in future educational and research efforts to improve infection control practices.

Baltimore↗
PubMed1997

Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2.

Stimulation of cell signaling cascades by oxidants may be important in the pathogenesis of pulmonary and pleural diseases. Here, we demonstrate in rat pleural mesothelial cells that apoptotic concentrations of crocidolite asbestos and H2O2 induce phosphorylation and activation of extracellular signal-regulated protein kinases (ERK). Activation of c-jun-NH2-terminal protein kinases (JNK)/stress-activated protein kinases was also observed in response to H2O2. In contrast, asbestos caused more protracted activation of ERK without JNK activation. Both H2O2- and asbestos-induced activation of ERK was abolished by catalase. Moreover, chelation of surface iron from crocidolite fibers or addition of N-acetyl-L-cysteine prevented ERK activation and apoptosis by crocidolite, indicating an oxidative mechanism of cell signaling. The MEK1 inhibitor PD-98059 abrogated asbestos-induced apoptosis, confirming a causal relationship between ERK activation and apoptosis. These results suggest that distinct cell-signaling cascades may be important in phenotypic responses elicited by oxidant stresses.

Acetylcysteine↗
PubMed1997

Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos.

We developed in situ dual-fluorescence detection techniques for measuring apoptosis and proliferation simultaneously in single dishes of cells. The deoxyribonucleic acid (DNA)-specific labeling method, terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), first was used in conjunction with a 4',6-diamidino-2-phenylindole (DAPI) counterstain to detect and measure morphologic characteristics of apoptotic rat pleural mesothelial (RPM) cells isolated from Fischer 344 rats and exposed to 300 microM hydrogen peroxide (H2O2). For this purpose, 100 TUNEL-positive nuclei were measured while being viewed with DAPI counterstaining for area, perimeter, longest diameter, and average diameter, using imaging software and an image-collection apparatus. We then exposed cells to a range of concentrations of crocidolite asbestos and putative apoptotic and mitogenic agents. Exposure to crocidolite asbestos (5 microg/cm2) caused a striking dose-dependent apoptotic response at 24 h, 48 h, and 72 h. The nonfibrous crocidolite analogue riebeckite failed to induce apoptosis. At 24 h, tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml) caused an increase in apoptotic nuclei. A second method, utilizing an antibody to 5'-bromodeoxyridine (BrdU) and oxazole yellow homodimer (YOYO), showed a dose-dependent increase in proliferation occurring in cells exposed to asbestos (5 microg/cm2) at 48 h and 72 h. In addition, increased numbers of rat pleural mesothelial (RPM) cells exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA), TNF-alpha, and epidermal growth factor (EGF) exhibited incorporation of BrdU at these time points, although total numbers of cells per unit area were unchanged. Results indicate a dynamic balance between apoptosis and increased DNA synthesis after exposure of mesothelial cells to asbestos.

Animals↗
PubMed1996

Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos.

Patterns of cell proliferation in lung and pleura and development of histopathologic lesions were studied in lungs from Fischer 344 rats after inhalation exposure to chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg/m3 air for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air (20 + 20 days). To assess cell proliferation rats were injected with 5-bromo-2'-deoxyuridine (BrdU) at various time points after initiation of exposure to asbestos. Image analysis was used to quantitate the effects of chrysotile and crocidolite on BrdU labeling indices in the following lung compartments: (1) interstitium, (2) alveolar duct region, (3) bronchial epithelium, and (4) visceral mesothelium. With the exception of mesothelium, which exhibited significant increases in BrdU incorporation in rats exposed to crocidolite at 20 + 20 days, asbestos-induced elevations in BrdU uptake in other compartments were transient with labeling comparable to sham controls at later time points. Histopathology of rat lungs revealed fibrotic lesions of a greater extent and severity at 20 days in rats exposed to crocidolite, but fibrosis occurred in both asbestos-exposed groups after an additional 20 days in clean air (20 + 20). Quantification of fiber burden in rat lung after inhalation of comparable airborne concentrations of either fiber type demonstrated that inhalation of crocidolite asbestos led to a higher fiber retention when compared to chrysotile asbestos. Our results indicate that chrysotile and crocidolite asbestos induce different patterns of cell proliferation in lung and pleural cells. The protracted increases in BrdU labeling of mesothelial cells by crocidolite may reflect increased retention of fibers and/or inherent differences between types of asbestos.

Administration, Inhalation↗
PubMed1996

Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos.

Asbestos causes protracted, dose-dependent increases in steady-state mRNA levels of the proto-oncogenes c-fos and c-jun, and AP-1 DNA-binding activity in normal rat pleural mesothelial (RPM) cells (1). To determine the phenotypic end points of overexpression of these early response genes by asbestos, both cell proliferation and apoptosis were examined in confluent RPM cells exposed to a range of concentrations (1.25 to 10 micrograms/cm2 dish) of crocidolite asbestos for 24 and 48 h. Quantitation of RPM cells pulsed with 5-bromo-2'-deoxyuridine revealed that asbestos caused dose-dependent decreases in cells undergoing DNA synthesis. Decreases in cell proliferation were accompanied by dose-related increases in apoptosis using (1) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (i.e., ApopTag technique), (2) 4',6-diamidino-2-phenylindole cell staining, and (3) fluorescent-activated cell sorter after incorporation of propidium iodide. Less striking but significant dose-related increases in apoptosis were observed in RPM cells exposed to H2O2 (300 microM), and no apoptosis was seen after exposure of cells to high concentrations (10 micrograms/cm2 dish) of glass beads. Our results are unique in that they demonstrate that asbestos induces apoptosis in mesothelial cells at concentrations eliciting increased expression of the proto-oncogenes c-fos and c-jun.

Animals↗
PubMed1995

Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos.

Biochemical and molecular markers of inflammation, cell proliferation, and pulmonary fibrosis were studied in lungs and bronchoalveolar lavage preparations from Fischer 344 rats at time periods from 3 to 20 days after inhalation of two airborne concentrations (0.18 and 8.2 mg/m3 air) of chrysotile asbestos. Additional groups of animals were examined for lung histopathology and cell proliferation with an antibody to 5-bromo-2'-deoxyuridine after exposure to asbestos for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air. Exposure to chrysotile at the higher concentration caused protracted increases in steady-state mRNA levels of manganese-containing superoxide dismutase and elevation in glyceraldehyde-3-phosphate dehydrogenase mRNA at 3 days, but levels of mRNAs encoding copper-zinc-containing superoxide dismutase, ornithine decarboxylase, and the proto-oncogene, c-jun were not statistically elevated from levels occurring in lung homogenates from sham control rats. Differential cell counts in bronchoalveolar lavage revealed an early infiltration of neutrophils that correlated with focal areas of increased cellularity and fibrosis in rat lungs at the higher concentrations of asbestos. However, elevations in lung hydroxyproline were not observed. Significant increases in epithelial cells of the bronchi, the interstitial compartment of the lung, and mesothelial cells incorporating 5-bromo-2'-deoxyuridine, an indication of DNA synthesis, were noted in the higher chrysotile group at 5 days, but labeling in all cell compartments was comparable with that occurring in sham controls at later time points. Indicators of inflammation, increased cell proliferation, and pulmonary fibrosis were not observed in the lungs of rats exposed to the lower concentration of chrysotile. Thus, results indicate that cellular and molecular markers of inflammation and proliferation in lung are dose-related and indicative of the histopathological development of asbestosis.

Administration, Inhalation↗
PubMed1994

Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos.

We focused here on steady-state mRNA levels of genes involved in antioxidant defense, i.e., manganese superoxide dismutase and copper-zinc superoxide dismutase, and in cell proliferation, i.e., ornithine decarboxylase, c-jun, and glyceraldehyde-3-phosphate-dehydrogenase in whole-lung homogenates from Fischer 344 rats at 3 h to 20 d after exposure to crocridolite asbestos. Changes in gene expression were correlated with histopathologic findings, total and differential cell counts in bronchoalveolar lavage, and levels of hydroxyproline in lung. Dosage-dependent increases in mRNA levels of antioxidant enzymes and proliferation-related genes were observed. Differential cell counts revealed a dose-related infiltration of neutrophils that preceded elevations in gene expression. Neutrophil infiltration into lung and focal lesions of fibrosis as well as increased levels of hydroxyproline were observed only at high concentrations of asbestos. These results indicate that high airborne concentrations of asbestos cause molecular changes in lung that may be related to antioxidant defense and the triggering of cell proliferation, a feature of asbestosis and lung cancer.

Administration, Inhalation↗
PubMed1993

Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity.

Cellular hypertrophy and hyperplasia and increased extracellular matrix deposition are features of tissue hypertrophy resulting from increased work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involved in these processes, however, remain unclear. Here we examined the effect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membranes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increased by 39% after 2 days of deformation (1.43 +/- .01 x 10(5) cells/membrane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). The medium from mechanically deformed cells was mitogenic for IMR-90 cells, with maximal activity in the medium from cells mechanically deformed for 2 days (stimulating cell replication by 35% compared with media control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is mediated by the release of autocrine growth factors.

Biomechanical Phenomena↗
PubMed1992

Intoxication and injury.

The relationship between alcohol use and injury severity was investigated in trauma patients admitted to a tertiary referral hospital during a 23-month period. Admission blood alcohol levels (BALs) were obtained on 427 trauma patients, who were stratified into three groups: those with no measurable blood alcohol, those within the legal limit of 100 mg/dL, and those over the legal limit or intoxicated. The no-alcohol group had significantly lower injury severity than the other two groups (p less than 0.001). Even when the BAL was well within the legal limit, injuries suffered by those in the alcohol-positive groups were more severe than those in the no-alcohol group. Confirmatory evidence of the effect of alcohol on injury severity was reflected by a 2.3% mortality in alcohol-negative patients compared with a 13.3% death rate in alcohol-positive patients (p less than 0.0001). To assess the potentially confounding effect of alcohol on injury scoring accuracy, we examined the change in Glasgow Coma Scale (GCS) scores following admission. No significant differences were found when admission GCS values were compared with GCS determinations made 24 hours following admission by separate observers. To correct for any potential bias as a tertiary referral center, repeat analysis with exclusion of transferred patients was done with essentially no change in results. Our data revealed a highly significant relationship between alcohol use, degree of injury, and resource consumption.

Adult↗
PubMed1992

Serum and bronchoalveolar lavage of N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis.

Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗