Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LEUKOCYTOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed2006

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.

Adenocarcinoma↗
PubMed1973

The effect of Bordetella pertussis on lymphocyte cyclic AMP metabolism.

Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic beta adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism. Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE(1)), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37 degrees C, the responses to all three agents were markedly inhibited. Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE(1) and methacholine responses were also inhibited suggests that blockade at the level of the beta adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2-1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml. The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities. The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.

Acetylcholine↗
PubMed1954

Experimental Staphylococcus infection in the hamster cheek pouch: the process of localization.

Small amounts of staphylococcus suspensions were injected into the cheek pouches of hamsters. Within 5 hours, the organisms were recovered from all outlying areas of the pouches, and in the following hours the entire structures showed vasodilation, edema, petechiae, and accumulation of leukocytes in the venules. Leukocytosis also occurred at this time. Between 24 and 48 hours, well defined abscesses developed at the sites of injection, and there was a sharp decrease in the bacteria in all other areas. From the 3rd day onward, organisms were only occasionally recovered from tissue outside the abscesses. At this period of localization, the generalized edema and petechiae also subsided, as did the leukocytosis. Localization of infection was not due to a walling off process, since the bacteria were disseminated through the entire pouches in the 1st few hours, but these organisms diminished rapidly, while those at the original injection sites continued to grow and reproduce for several days. Localization of infection appeared to be due to the inability of the bacteria carried away from the site of injection to reproduce. This in turn may have been due to dilution, to lack of sufficient toxin to produce a necrotic substrate, or to greater accessibility of these organisms to phagocytes.

Animals↗
PubMed1997

Serotype-related differences in inflammatory response to Streptococcus pneumoniae in experimental meningitis.

It has been suggested that serotype influences severity of experimental pneumococcal meningitis. This hypothesis was tested with strains of serotypes 1, 5, 6B, 7F, 14, and 23F, prevalent in Israel, in an experimental rabbit model. Cerebrospinal fluid (CSF) bacterial titers, leukocyte densities, concentrations of lactate, protein, and glucose, tumor necrosis factor-alpha levels, brain water content, and cerebral blood flow were measured 18 h after inoculation of pneumococci. Serotypes 5 and 7F exhibited mild inflammatory responses (leukocytosis <1000/mm3, lactate <4 mmol/L); types 6B, 14, and 23F showed severe inflammatory responses (leukocytosis >5000/mm3, lactate >10 mmol/L); serotype 1 had intermediate inflammatory responses but exceptionally high CSF bacterial titers. Leukocyte count correlated with all other variables; lactate with all except brain water content. On the basis of 6 Streptococcus pneumoniae serotypes, three discrete levels of inflammatory responses could be delineated in experimental pneumococcal meningitis.

Animals↗
PubMed1998

A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.

Animals↗
PubMed2006

Videolaparoscopic cholecystectomy for acute cholecystitis: analyzing conversion risk factors.

We examined a series of 176 consecutive patients scheduled for videolaparoscopic cholecystectomy for acute cholecystitis to identify the independent parameters most likely to lead to conversion to laparotomy. This prospective study was conducted from June 2001 to December 2003 on 176 consecutive patients who were scheduled for videolaparoscopic cholecystectomy for acute cholecystitis. Of the 176 patients, 119 (group A) underwent videolaparoscopic chlecystectomy, and 57 (32.3%) were converted to laparotomy (group B). Patients were assessed for gender, age, time between onset of symptoms and surgery, previous surgery, ASA (American Society of Anesthesia) risk, leukocytosis, echotomographic findings, average operating time, intra- and post-operative complications, and conversion rate. Our study found that the parameters of age, ASA risk, duration of symptoms, leukocytosis, and operative time are independent conversion risk factors.

Aged↗
PubMed1993

A new endoscopic drainage technique for pancreatic abscesses.

Acute pancreatitis sometimes leads to pancreatic abscess with a high mortality rate when appropriate drainage is not applied. Pancreatic pseudocysts are also major complications of pancreatitis, which usually need to be treated only when they are symptomatic; they sometimes lead to disseminated intravascular coagulopathy or intraabdominal bleeding if they maturate. Conventional pancreatic drainage operations have sometimes been so invasive that they cannot be applied for severe cases with renal failure and disseminated intravascular coagulopathy. To avoid the risks of conventional drainage operations for pancreatic abscesses, a low invasive and effective percutaneous drainage technique guided by a laparoscope was developed and employed to a high-risk patient with post-pancreatitic pancreatic abscess. After the operation, leukocytosis and high fever improved dramatically. One year after discharge from the hospital, no recurrence of abscesses or leukocytosis have been found. Thus, this technique should be considered as a first option for the pancreatic drainage operation.

Abscess↗
PubMed2002

The International Prognostic Factors Project score for advanced Hodgkin's disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation.

BACKGROUND: The International Prognostic Factors Project on Advanced Hodgkin's Disease developed a seven-factor prognostic score consisting of serum albumin, hemoglobin, gender, stage, age, leukocytosis and lymphocytopenia for newly diagnosed Hodgkin's disease patients who receive chemotherapy. The purpose of this study was to determine whether this prognostic score would also be useful for Hodgkin's disease patients undergoing autologous hematopoietic stem cell transplantation. PATIENTS AND METHODS: We performed a retrospective review of 379 patients who had autologous transplants for Hodgkin's disease, at the University of Nebraska Medical Center between October 1984 and December 1999. Multivariate analysis was performed to determine whether the prognostic factors identified by the International Prognostic Factors Project adversely influenced event-free survival (EFS) or overall survival (OS). RESULTS: Low serum albumin, anemia, age and lymphocytopenia were associated with poorer EFS and OS. Gender, stage and leukocytosis were not associated with significantly poorer outcomes. Estimated 10-year EFS was 38%, 23% and 7% for patients with 0-1, 2-3 or > or =4 of the adverse prognostic characteristics identified by the International Prognostic Factors Project, respectively. CONCLUSIONS: The prognostic score for advanced disease is also useful for relapsed and refractory Hodgkin's disease patients undergoing high-dose therapy followed by autologous hematopoietic stem cell transplantation.

Adolescent↗
PubMed2005

Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an unfavorable clinical course and are under-represented in clinical trials. The aim of this study was to analyze the prognosis and treatment outcome of elderly AML patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or older at our hospital. Prior to study initiation, we designated 13 variables to be analyzed for their impact on complete remission (CR) rate and overall survival (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced the achievement of CR. Multivariate analysis also determined five poor prognostic factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was not an independent contributing factor in terms of either CR attainment or OS duration. Low-risk patients, who possessed one or less non-leukocytosis poor prognostic factor, had significantly longer disease-free survival and OS than their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk-stratified at diagnosis. Anthracycline-based induction chemotherapy would be the best therapeutic option for such patients.

Acute Disease↗
PubMedDate not supplied

Update on spinal epidural abscess: 35 cases and review of the literature.

Thirty-five cases of spinal epidural abscess were evaluated retrospectively and compared with 153 cases reported in the literature. As in other series, Staphylococcus aureus was the major pathogen. Patients with acute abscesses had fever, leukocytosis, and purulence at surgery. Patients with chronic abscesses had less fever and leukocytosis, more granulation tissue at surgery, and a greater delay in diagnosis but retained the potential for rapid neurologic deterioration. In contrast to other studies, abscesses in both the lumbar and anterior spinal compartments and patients with specific sources of infection occurred with greater frequency. Myelography was the diagnostic method of choice. Only four of nine patients had diagnostic computed tomography. Earlier diagnosis and treatment led to a significant improvement in outcome. Both steroid administration and greater neurologic impairment adversely affected outcome. Neurologic improvement following surgery was dependent on the duration of the deficit. A combination of antibiotics and surgical drainage remains the treatment of choice.

Abscess↗
PubMedDate not supplied

The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a dramatic complication of ovulation induction. In its most severe form, OHSS is characterized by massive cystic enlargement of the ovaries associated with third space fluid shift, resulting in the formation of ascites and pleural effusion. Ascites developes because of increased peritoneal capillary permeability. In this study we examined the role of vascular endothelial growth factor (VEGF) and interleukins in the pathogenesis of increased capillary permeability. VEGF is a member of the family of heparin binding proteins that act directly on endothelial cells to induce proliferation and angiogenesis. VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicular development and subsequent to ovulation by granulosa and theca cells. Therefore, VEGF is ideally positioned to provoke the increased permeability of theca blood vessels that occurs shortly before ovulation. Hybridization studies in the rat and primate ovary have demonstrated VEGF mRNA expression predominantly after the luteinizing hormone (LH) surge known to be essential for OHSS. The gonadotrophin-releasing hormone antagonist results in a decreased mRNA expression, implying such expression is dependent on LH. The expression of VEGF mRNA has been recently shown to be enhanced by human chorionic gonadotrophin (HCG) in a dose- and time-dependent fashion. These studies confirm the timely association between VEGF and HCG that has been clinically known for many years to be integral in the development of OHSS. VEGF concentrations in serum, peritoneal fluid and follicular fluid of patients at risk for OHSS have been shown to be significantly related to the development of the syndrome. Furthermore, the kinetics of VEGF in the plasma of patients who actually develop severe OHSS are closely correlated with the clinical course of the syndrome and with certain biological characteristics of OHSS and of capillary leakage, such as leukocytosis and increased hematocrit. Studies on ascitic fluid from patients with sever OHSS have proved that VEGF is the major capillary permeability agent. Incubation with VEGF antiserum decreased the vascular permeability activity by 70%. Interleukin-2 (IL-2) is the first of a series of lymphocytotrophic hormones to be recognized as pivotal for the regulation of immune response. However, hard data to confirm its central role in the pathogenesis of OHSS are still lacking, despite the fact that some preliminary studies suggest a positive association between the pooled follicular fluid IL-2 concentration and the development of OHSS. IL-6 is a mediator of the acute phase response to injury, a systemic reaction characterized by leukocytosis, increased vascular permeability and increased synthesis of acute phase proteins by the liver. Significantly higher serum and ascites IL-6 concentrations were seen in OHSS patients. The immunohistochemical localization pattern suggested that IL-6 is LH or HCG dependent. However, the use of IL-6 as a predictor for the occurrence of OHSS has not been successful. The kinetics of IL-6 in patients with severe OHSS are correlated with the clinical symptoms and the biochemical parameters known to be associated with the severity of the syndrome, suggesting a possible role for IL-6. Further molecular biology studies similar to those performed on VEGF are needed to confirm if this interleukin is central in the cascade of events. IL-8 is a chemoattractant, activating cytokine and a potent angiogenic agent. The peritoneal fluid levels is increased in patients with severe OHSS; its concentration in peritoneal fluid is increased inpatients with severe OHSS. The place of this interleukin in the cascade of events is as yet undetermined and further studies are needed. In conclusion, molecular biology and clinical studies strongly suggest that VEGF is the principal mediator by which HCG might increase capillary permeability in OHSS.

Animals↗
PubMed1988

Microbiological and clinical significance of a new property of defective lysis in clinical strains of pneumococci.

A pneumococcal isolate that caused relapsing meningitis in a patient infected with human immunodeficiency virus (HIV) was found to display an unusual response to penicillin--rapid death but a striking lack of cellular lysis. This lytic defect was also detected in all four pneumococcal isolates from three additional HIV-infected patients and in more than half of the clinical isolates from patients with bacteremia. In a rabbit model of meningitis, the lysis-defective strain remained cryptic, with a delay of 5 h in the onset of leukocytosis in cerebrospinal fluid. A marked burst of leukocytosis was associated with ampicillin-induced lysis of a lysis-sensitive strain but not of a lysis-defective strain. Pneumococcal clinical isolates have different lytic responses to penicillin; defective lysis may adversely affect the course of meningitis, an observation suggesting that autolysins play a role in modulating infectious diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The biologic activities of peptidoglycan in experimental Haemophilus influenzae meningitis.

While gram-positive bacterial cell walls are known to incite inflammation, the contribution of gram-negative peptidoglycan to disease has not been characterized. The ability of cell wall, purified peptidoglycan, and soluble peptidoglycan subcomponents from Haemophilus influenzae to provoke inflammation was determined in a rabbit model of meningitis. Haemophilus peptidoglycan, with or without associated proteins, produced brain edema at > or = 0.1 micrograms/mL of cerebrospinal fluid (CSF); leukocytosis and protein accumulation in CSF occurred only at > or = 10.0 micrograms/mL of CSF. Solubilized peptidoglycan was 10-fold more active than intact cell wall. The bioactivity of peptidoglycan from ampicillin-resistant H. influenzae was at least twofold greater than that of ampicillin-sensitive strains. Consistent with these pathologic effects of purified peptidoglycan, ampicillin-induced bacterial lysates in which endotoxin was neutralized induced brain edema and protein influx but little leukocytosis. Thus, peptidoglycan seems to contribute to the pathology of gram-negative meningitis, particularly brain edema.

Ampicillin Resistance↗
PubMed1998

Rifampicin-induced acute renal failure: a series of 60 patients.

BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced ARF have been published, but systematic data on this condition are not available, in view of the disparate nature of the observations. METHODS: We retrospectively assessed prevalence, clinical and biochemical features, and prognostic factors of 60 consecutive cases (41 males/19 females, age 22-68 years), who were admitted to the Iasi Dialysis Centre from 1987 to 1995 for acute renal failure (ARF) following re-treatment with rifampicin. RESULTS: The clinical appearance consisted mainly of gastrointestinal and 'flu-like' symptoms and clinical signs of intravascular haemolysis (the latter in 17% of cases). Frequent laboratory findings were anaemia (96% of cases), leukocytosis (63%), and thrombocytopenia (50%). Severe anaemia was associated with marked haemolysis (25% cases), thrombocytopenia, longer anuria, and slower rate of renal function recovery. Signs of hepatic injury were found in 25% of patients, but it did not seem to affect the outcome of renal function. Prognostic factors in post-rifampicin ARF proved to be the following: the duration of the anuric phase (correlated with the number of dialysis sessions and with the rate of decrease of azotaemia) and the severity of the immunological abnormalities and inflammatory syndrome (haemolysis, leukocytosis, hypergammaglobulinaemia). Post-rifampicin ARF accounted for 16.6% of all ARF cases hospitalized in our Centre during the studied period. Its clinical course was favourable; the mortality rate was only 1.6% (1 case), compared to a 20% general mortality rate among all ARF patients. Full recovery of renal function was achieved in 40% and 96% of patients, 30 and 90 days respectively from onset. CONCLUSIONS: ARF after treatment with rifampicin is not an uncommon condition, especially when tuberculosis prevalence is high, but renal prognosis is usually favourable. Thrombocytopenia, immune haemolytic anaemia, and intravascular haemolysis are frequent complications which are associated with a more severe renal injury.

Acute Kidney Injury↗
PubMed2003

Palliative irradiation of the spleen.

We analyzed the efficacy of splenic irradiation in a population of patients with hematologic diseases. The records of the Radiation Oncology Division, Naval Medical Center San Diego were retrospectively reviewed for all patients treated with splenic irradiation (SI) between January 1, 1990 and March 1, 2001. The charts of 17 patients were identified: 5 patients had chronic myelogenous leukemia, 4 had chronic lymphocytic leukemia, 4 had idiopathic myelofibrosis, 2 had polycythemia vera, and 1 patient each had idiopathic thrombocytopenic purpura and acute myelogenous leukemia. Patient ages ranged from 37 to 88 years. Sixteen of 17 suffered from symptomatic splenomegaly. Twenty-six courses of splenic irradiation were delivered to these 17 patients. Treatment courses generally consisted of two fractions of 50 cGy in the first week, two fractions of 75 cGy the second week, and two fractions of 100 cGy the third week. Blood counts were checked prior to each treatment. Seven of the 17 patients died 1 month or less after SI due to the terminal nature of their disease. Twenty-two of 25 treatment courses for splenomegaly resulted in decreased pain and symptoms. Five patients required two treatment courses for splenomegaly, and one patient required five treatment courses. Three of four patients treated for thrombocytopenia demonstrated improvement, but only one was evaluable for more than 2 weeks due to disease-related mortality. Three of five patients treated for leukocytosis had significant improvement. In general, patients suffered few significant complications from this palliative intervention. Splenic irradiation can effectively palliate symptomatic splenomegaly in patients for whom splenectomy is not an option. Retreatment is possible. Splenic irradiation is less effective in the treatment of thrombocytopenia or leukocytosis.

Adult↗
PubMed1998

Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study.

OBJECTIVE: This prospective trial examined the efficacy of using bronchoalveolar lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain (GS) for dictating empiric therapy. SUMMARY BACKGROUND DATA: Posttraumatic nosocomial PN remains a significant cause of morbidity and mortality. However, its diagnosis is elusive, especially in multiply injured patients. The systemic inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state is common in trauma patients, especially patients with pulmonary contusion. Bronchoscopy with BAL with quantitative cultures of the lavage effluent may distinguish between PN and systemic inflammatory response syndrome, and GS of the lavage effluent may guide empiric therapy before quantitative culture results. METHODS: Mechanically ventilated trauma patients with a clinical diagnosis of PN (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony-forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome was made. Causative organisms for PN were compared to GS. RESULTS: Over a 2-year period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women; mean age, 41). The mean injury severity score was 30. Sixty percent of the patients had pulmonary contusion, and 59% were cigarette smokers. The overall incidence of PN was 39% and was no different regardless of the number of BALs a patient had. The false-negative rate of BAL was 7%. GS identified gram-positive organisms in 80% of patients with gram-positive PN and 40% of patients with gram-negative PN. GS identified gram-negative organisms in 52% of patients with gram-positive PN and 77% with gram-negative PN. The duration of the intensive care unit stay relative to the timing of BAL was beneficial for guiding empiric therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram-positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after week 1. CONCLUSIONS: Bronchoscopy with BAL is an effective method to diagnose PN and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be adjusted to the duration of the intensive care unit stay because the causative bacteria flora changes over time. GS of BAL effluent correlates poorly with quantitative cultures and is not reliable for dictating empiric therapy.

Adult↗
PubMed2002

Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis-associated lung injury.

OBJECTIVE: Activated neutrophils are presumed to injure pulmonary endothelium by releasing oxygen radicals, proteases, and proinflammatory cytokines. Standard counting methods do not distinguish between leukocytosis, neutrophil sequestration, and activation. We used leukocyte uptake of the glucose analog [18F]fluorodeoxyglucose (18FDG), which indicates postmigrational neutrophil activity, to identify and quantify the relationship between acute respiratory distress syndrome and neutrophil activation in experimental pancreatitis in rats. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Mild and severe pancreatitis models in the rat. INTERVENTIONS Pulmonary (with muscle as control) leukocyte accumulation was assessed by uptake of technetium-99m-labeled chemotactic peptide (fMLFK) and confirmed by measurement of myeloperoxidase activity. Neutrophil activity was assessed by 18FDG uptake. Tissue-to-blood ratios for fMLFK, 18FDG, and leukocytes were calculated to control for background. Neutrophils were counted in histologic sections of saline-perfused lungs. Bronchoalveolar lavage fluid was assessed for neutrophil migration and autoradiographed for intracellular 18FDG localization. MEASUREMENTS AND MAIN RESULTS: Lung myeloperoxidase activity, 18FDG, and peripheral white blood cells all significantly increased in both mild and severe pancreatitis, but lung fMLFK only increased in severe pancreatitis. After correction for blood background, only 18FDG in lung (but not muscle) was significantly increased in pancreatitis (severe > mild > normal, p<.001). Histologic analysis showed significant increase in extravascular (migrated) neutrophils only in severe pancreatitis. Autoradiography of bronchoalveolar lavage fluid confirmed the 18FDG within intra-alveolar neutrophils. CONCLUSIONS: In this pancreatitis model of acute respiratory distress syndrome, there was nonspecific and noninjurious increase of neutrophils in the lung, attributable in part to background leukocytosis and to intravascular sequestration. However, 18FDG uptake uniquely showed that interstitial and intra-alveolar neutrophil migration and activation occurred in severe but not in mild pancreatitis, consistent with clinical correlations between acute respiratory distress syndrome and severity of underlying systemic disease. 18FDG uptake, which is also accessible by positron emission tomography scanning, better quantitates the contribution of activated neutrophils to tissue injury than other measurements of neutrophil accumulation or sequestration.

Animals↗
PubMedDate not supplied

Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, endothelin-1, and C1 esterase inhibitor.

Interleukin-2 (IL-2) promotes multisystem organ edema, lung neutrophil sequestration, and platelet activation through alterations in the microvascular barriers and permeability. IL-2, complement, platelet, and vascular endothelial activation were evaluated in 60 patients. One-factor analysis of variance indicated a significantly increased absolute neutrophil count on day 1 (p < 0.0001) and decreased C1Inh, p = 0.0001, with elevated IL-2 levels in the 20% to 40% group (p = 0.008). Endothelin-1 levels were significantly increased in the 20% to 40% total body surface area group on day 5. The absolute neutrophil count was significantly reduced in both groups, and C1Inh rose to near normal levels by day 5. No significant elevations of 6-keto prostaglandin F1 alpha were observed on day 1 or day 5 in the < 40% total body surface area group; however, these levels were significantly elevated on day 1 in the > 40% total body surface area group. Thromboxane B2 and platelet factor 4 were significantly elevated in all groups (p = 0.001) on days 1 and 5. Regression analysis implicated infection as a significant contributor to the IL-2 variations (r2 = 0.61), with inhalation injury minimally affecting IL-2 plasma levels (r2 = 0.09). Generalized edema increased with increasing burn wound size in parallel with elevated IL-2 and endothelin-1 levels, reduced C1Inh levels, and leukocytosis in the first week after thermal injury. These data suggest that there are dynamic interactions among the endothelium, cytokine stimulation, leukocytosis, complement, and platelet activation in promoting the microvascular permeability.

Adolescent↗