Blood phagocyte luminescence: gauging systemic immune activation.
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Animals↗
Biomedical subjects
R C Allen
Publications and source records attributed to R C Allen.
Luminescence studies of the phagocyte response to endotoxin infusion into normal human subjects: multiple discriminant analysis of luminescence response and correlation with phagocyte morphologic changes and release of elastase.
A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects. The subjects were closely monitored clinically, and extensive chemical, hematological and coagulation measurements were taken during the pretreatment, early (symptomatic, 1-8 h post-LPS), and late (asymptomatic, 12-48 h post-LPS) phases of acute inflammation. BLS assessment included measurement of basal and PMA-stimulated phagocyte oxidase and myeloperoxidase (MPO) activities, and also included measurement of circulating (COR) and PAF-primed maximum (MOR) opsonin receptor-dependent phagocytic activities. Basal oxidase activity peaked at T + 1 h and showed an additional peak at T + 24 h post-LPS. The COR activity also peaked at 1-2 h, but remained elevated through T + 24 h post-LPS, while the basal MPO activity peaked only once at T + 1 h. We concluded that while MPO evidence of phagocyte respiratory activation returned to baseline by T + 4 h, COR evidence of receptor expression (receptor alert) remained elevated through T + 24 h. During this early (0-8 h) period, elastase/alpha 1AT complex concentration peaked at T + 3-4 h and again at T + 8 h. Peak numbers of circulating polarized and vacuolated phagocytes also appeared at T + 3 h and 7 h. We concluded that there was biochemical and morphological evidence of continuing phagocyte activity beyond T + 4 h to T + 8 h, and that this corresponded with the period during which the subjects were symptomatic. In addition, the appearance of a second peak of basal oxidase activity at T + 24 h, multiple discriminant analyses of all the luminescence data, and the sustained elevation of lactate suggested that there was a later second stage (T + 12 h to 48 h) of the human response to endotoxin, during which time the subjects were asymptomatic.
Adult↗
Enzymatically inactive eosinophil peroxidase inhibits proinflammatory cytokine transcription and secretion by macrophages.
The present investigators have reported previously that macrophages (Mphi) can bind either myeloperoxidase (MPO) or eosinophil peroxidase (EPO) resulting in enhanced cytotoxicity to Candida albicans. Since MPO was shown to be immunomodulatory, the present study was initiated to determine whether either EPO or partially fragmented EPO (fgEPO) also modulated cytokine secretion. Murine peritoneal Mφ simultaneously stimulated with fgEPO and one of the following, (1) LPS, (2) mannosylated bovine serum albumin (mBSA), (3) interferon-gamma (IFN-gamma), or (4) Poly I:C, demonstrated both dose- and time-dependent decreases in TNF-alpha and IL-6 and a dose-dependent decrease in IFN-alpha/beta. The mRNA levels of Mphi exposed to fgEPO and mBSA demonstrated that fgEPO modulated Mphi cytokine function by decreasing TNF-alpha and IL-6 mRNA transcripts without altering transcription of TGF-beta or GM-CSF. These results demonstrate a possible interaction between the Mphi and eosinophil that could result in reduction of inflammation.
Animals↗
Priming of blood neutrophils in children with cystic fibrosis: correlation between functional and phenotypic expression of opsonin receptors before and after platelet-activating factor priming.
Blood phagocyte opsonin receptor CR1 (CD35) and CR3 (CD11b) functions were examined in cystic fibrosis (CF) patients with endobronchial Staphylococcus aureus or Pseudomonas aeruginosa chronic infection, CF patients without infection, heterozygous, non-CF patients with chronic pulmonary infection, and healthy controls. Circulating and platelet-activating factor (PAF)-primed phagocyte luminol luminescence responses to complement-opsonized zymosan were increased in both groups of infected CF and non-CF children relative to uninfected CF children and healthy control children and adults. The ratio between circulating and PAF-primed phagocyte responses was significantly elevated in all children with CF, and in these, the ratio could serve as an indicator of response to antibiotic treatment. The ratios of circulating and PAF-primed phenotypic expression for CR1, CR3, and FcgammaRIII (CD16), but not FcgammaRII (CD32), correlated with the functional ratios. Phagocyte opsonin receptor response capacity might be used for evaluation of inflammation and infection in CF patients.
Adolescent↗
Polymorphonuclear neutrophil chemiluminescence in whole blood from blunt trauma patients with multiple injuries.
BACKGROUND: Studies using isolated polymorphonuclear neutrophils (PMNs) indicate that trauma is associated with altered function of PMNs. Because isolation of PMNs can itself alter the function of these cells, we examined the relationships among measures of injury severity and several indices of PMN function using whole blood samples from trauma patients. METHODS: Whole blood samples were obtained from 12 blunt trauma patients with multiple injuries in the intensive care unit of a Level I trauma center within 24 hours of admission and from 11 healthy volunteers. Samples were assayed for PMN chemiluminescence (CL) in response to a complement receptor 3 (CR3)-dependent agonist and for CD11b (CR3) expression. Common clinical parameters were correlated with CL and CR3 expression. RESULTS: The CL ratio (i.e., unprimed/primed CL) was significantly correlated with initial base deficit (BD), Injury Severity Score (ISS), CR3 expression, units of packed red blood cells transfused during the interval before blood sampling, and length of intensive care unit stay (survivors only). In contrast, BD did not correlate with units of red blood cells transfused or length of stay. Similarly, ISS did not correlate with length of stay. CONCLUSION: Significant correlations were observed between CL ratios and CR3 expression, ISS, initial BD, length of stay, and units of blood given. These data suggest that measuring CL produced by PMNs in whole blood is a potentially useful way to assess injury severity. Whereas the initial BD and ISS are indicators of how badly injured a patient is at the time of entry into a trauma center, the CL ratio may be a more useful indicator of both injury severity and prognosis.
Blood Transfusion↗
Impaired phagocyte oxidative capacity in patients with human immunodeficiency virus infection.
Bacterial infections that may be related to impaired phagocyte function often develop in patients infected with human immunodeficiency virus (HIV). We examined the oxidative capacity of circulating phagocytes in 78 HIV+ patients and 31 control subjects by measuring chemiluminescence with a whole blood assay. Phagocytes were stimulated with zymosan opsonized with human complement (hC-OPZ) or immunoglobulin (hI-OPZ) with or without exogenous primers. Patients with CD4+ < 500/microL showed reduced whole blood chemiluminescence at maximal opsonin receptor (MOR) activity after priming in response to hC-OPZ relative to control subjects, and the difference was significant for patients with CD4+ < 100/microL. Patients had lower absolute phagocyte counts; however, the chemiluminescence activity calculated per phagocyte count was significantly depressed in advanced HIV infection, indicating the impairment of phagocytic cell function and a reduction in number. Data were similar when hI-OPZ was used as a stimulus. The chemiluminescence of unprimed phagocytes at circulating opsonin receptor (COR) activity relative to maximally primed phagocytes (COR/MOR ratio) was significantly higher for HIV+ patients as compared with control subjects and indicates a defect in phagocyte priming. Alternatively, the phagocytes do not increase chemiluminescence with priming because they have already been primed or activated in vivo. In late-stage disease, decreased opsonin receptor-dependent respiratory burst activity contributes to the risk of secondary bacterial infections.
Adult↗
Reflex sympathetic dystrophy in a 12-year-old twin with comorbid conversion disorder in both twins.
A case of reflex sympathetic dystrophy is presented in a 12-year-old girl with comorbid conversion disorder. Her identical twin also had a conversion disorder. This is the first reported case of coexistence of reflex sympathetic dystrophy and conversion disorder. It is important for clinicians to be aware that these conditions may coexist since the presentation of symptoms differ, even though there are shared features of treatment.
Child↗
Perpetuation of inflammation associated with experimental arthritis: the role of macrophage activation by neutrophilic myeloperoxidase.
Rheumatoid arthritis (RA) is characterized by an abnormal cellular and cytokine infiltration of inflamed joints. This study addresses a previously unrecognized interaction between neutrophilic-myeloperoxidase (MPO) and macrophages (Mphi) which could explain the perpetuation of inflammation associated with RA. A monoarticular arthritis was induced in female Lewis rats by injection of streptococcal cell wall extracts (PG-APS). After swelling and erythema subsided, joints were re-injected with one of the following: porcine MPO or partially inactivated MPO (iMPO). Injection with either MPO or iMPO induced a 'flare' of experimental RA. Blocking the Mphi-mannose receptor by mannans, ablated exacerbation of disease. These results indicate that MPO or iMPO can play a pivotal role in the perpetuation but not initiation of this RA model.
Animals↗
Analysis of amplified fragment-length polymorphisms (VNTR/STR loci) for human identity testing.
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Alleles↗
Erbium:YAG laser-assisted cataract surgery.
BACKGROUND AND OBJECTIVE: To assess the safety and efficacy of erbium:YAG laser-assisted cataract removal. PATIENTS AND METHODS: A total of 15 patients underwent cataractous lens removal. All the patients had a visual acuity of 20/50 or worse secondary to senile cataract. The endothelial cell count was calculated preoperatively and at 6 weeks postoperatively. A 2.94-micron-wavelength erbium: YAG laser with a zirconium-fluoride fiber optic and silica tip was used to fracture and emulsify the nucleus. The erbium:YAG laser was chosen due to its high absorption in water, a primary component of a cataractous lens. RESULTS: The postoperative visual acuity was 20/30 or better in all the eyes that were treated with surgery. The endothelial cell loss at 3 months was 0% to 10%. No laser-related complications were noted. A conversion to an ultrasound surgical technique was utilized in six cases. Vitreous loss occurred in one case due to the posterior extension of an anterior capsulotomy tear. CONCLUSION: This study demonstrated the ability of an erbium:YAG laser system to safely and effectively emulsify the lens nucleus. Laser-assisted cataract surgery is a promising new clinical procedure.
Aged↗
Maintenance and down-regulation of primed neutrophil chemiluminescence activity in human whole blood.
Priming of polymorphonuclear neutrophils (PMN) in whole blood (by tumor necrosis factor alpha and interleukin-8 for enhancement of luminol-dependent chemiluminescence induced by human complement-opsonized zymosan) was stable for 120 min. In contrast, priming of isolated PMN in plasma-free suspension for responses to opsonized zymosan, formyl-methionyl-leucyl-phenylalanine, and phorbol myristate acetate was markedly less stable. Decay of priming was not due to irreversible inactivation of the terminal CL production machinery because PMN could be reprimed by platelet-activating factor or leukotriene B4. The tumor necrosis factor-alpha-primed state of isolated PMN was stabilized by host plasma in a concentration-dependent fashion. We conclude that PMN priming results in a dynamic state that is reversible. Our findings suggest the existence of blood-borne components that may act to stabilize or modify PMN priming.
Down-Regulation↗
Hemodialysis access graft stenosis: percutaneous transluminal angioplasty.
Maintenance of dialysis access continues to plague care of the patient with ESRD. Because of the poor outcomes from surgical revision, there is increasing interest in balloon angioplasty as a technique for dilating stenoses in the functioning, but compromised graft. Forty patients treated with percutaneous transluminal angioplasty (PTA), without subsequent intervention, for graft dysfunction were retrospectively studied. Time to thrombosis of the graft was noted. Patency was determined using the Kaplan-Meier technique. Patency following PTA at 1, 6, and 12 months was 76, 27, and 10%. Patency following PTA of arteriovenous graft stenoses results in disappointing medium and long-term patency. Alternate strategies for improving patency of these conduits should be explored.
Angioplasty, Balloon↗
Transplantation of testis-derived Sertoli cells into the mammalian brain.
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Animals↗
Carotid endarterectomy in patients less than 50 years old.
PURPOSE: The purpose of this study was to compare the results of carotid endarterectomy (CEA) in a young population with premature atherosclerosis with the results of an older control group, examining perioperative morbidity and mortality data, recurrent stenosis and symptoms, late stroke, and survival data. METHODS: We retrospectively studied 26 patients less than 50 years old (mean, 43.2 +/- 3.8 years) and 30 patients greater than 55 years old (mean, 69.1 +/- 7.4 years) who underwent CEA during the same time period. Data were obtained regarding demographics, atherosclerotic risk factors, indication for CEA, perioperative complications, recurrent stenosis and symptoms, late stroke, and survival. RESULTS: Smoking was more prevalent among young patients who underwent CEA (92% vs 70%; p = 0.036). Young patients were also more likely to be symptomatic at presentation (92% vs 57%; p = 0.003). The perioperative mortality rate (0% vs 0%) and neurologic morbidity rate (0% vs 3%; p = 1.000) were low for the study patients. During a mean follow-up of 67 +/- 42.7 months, there was no significant difference in survival rate (5-year survival rate, 93% vs 81%; p = 0.373), rate of late ipsilateral (4% vs 3%) and contralateral (4% vs 3%) stroke, restenosis and occlusion (26.9% vs 14.3%), recurrent symptoms (22% vs 17%), reoperation (11.5% vs 5.7%), or contralateral disease (17% vs 23%) development that required surgery for the study or the control cohorts. CONCLUSIONS: Our data show that there is a high incidence of smoking and symptomatic presentation among young patients in whom carotid occlusive disease develops. CEA may be performed in young patients with low perioperative morbidity and mortality rates. Recurrent disease, late stroke, and survival rates are not significantly different than for older patients. Follow-up with serial duplex ultrasound and reoperation for symptomatic and high-grade asymptomatic restenosis may decrease the risk of late stroke.
Adult↗
Central venous stenosis in the hemodialysis patient: incidence and efficacy of endovascular treatment.
Central venous stenosis occurs as a complication of central venous catheterization and significantly complicates delivery of dialysis through arteriovenous grafts in the ipsilateral upper limb. This report includes two separate studies. Functioning expanded polytetrafluorethylene grafts have been prospectively evaluated using duplex scanning and angiography performed in all patients with stenoses > 50%. From this, it has been prospectively established that the incidence of unsuspected central venous stenoses in patients with functioning grafts is 29%. In the second part of the report, the authors' experience in the treatment of 25 central venous stenoses with percutaneous angioplasty and stent placement has been retrospectively reviewed. Initial technical success rate was 88%. Primary patency was 84% at 1 month, 42% at 6 months, and 17% at 1 year. Mean primary patency was 5.7 months. Stents were placed in five patients. Prevention of central venous stenosis by avoiding subclavian catheterization is optimal. Balloon angioplasty provides short-term patency, but it is the only option in most cases. The role for endovascular stent placement remains to be defined but early results are not optimistic.
Angioplasty, Balloon↗
Macrophage-mediated candidacidal activity is augmented by exposure to eosinophil peroxidase: a paradigm for eosinophil-macrophage interaction.
Various disease states are associated with eosinophilia and the release of eosinophil peroxidase (EPO) into the microenvironment. The present study targets the effects of low levels of EPO on macrophage (M phi) phagocytosis and intracellular killing of Candida albicans as well as M phi oxidative activity measured as the luminescence product of luminol dioxygenation. Resident murine peritoneal M phi were exposed to various concentrations of EPO. Chemiluminescence data indicate that nanomolar concentrations of EPO markedly enhanced the dioxygenation activity (respiratory burst) of M phi. In other studies, the exposure of M phi to 0.17 microM EPO for 10 min. enhanced M phi-mediated candidacidal activity 10 fold. The above data indicate that EPO enhances certain M phi functions. Also the results illustrate a previously un-recognized interaction between eosinophils and M phi and implicate yet another possible role for EPO in host defenses against disease.
Animals↗
In vivo effects of recombinant human granulocyte colony-stimulating factor on neutrophil oxidative functions in normal human volunteers.
The effect of daily in vivo granulocyte colony-stimulating factor (G-CSF) treatment on neutrophil function was studied over a 14-day period using a luminescence system for differential measurement of oxidase and myeloperoxidase (MPO) dioxygenation activities in whole blood. Opsonin receptor-mediated phagocyte functions were also measured with this system. G-CSF produced a dose-dependent neutrophil leukocytosis and a proportional increase in oxidase activity per volume of blood. The oxidase activity per neutrophil remained relatively constant throughout the test period. However, both chemical- and opsonin-stimulated MPO oxygenation activities per neutrophil were greatly increased by treatment with maxima correlating temporally to initial G-CSF exposure during the early mitotic phase of neutrophil development. The possibility that peroxynitrite contributes to this maximum luminol-dependent activity was tested, but neither superoxide dismutase, a competitive inhibitor of peroxynitrite production, nor N-methyl-L-arginine, an inhibitor of nitric oxide synthase, exerted a significant inhibitory effect.
Adult↗
What are the characteristics of the ideal endovascular graft for abdominal aortic aneurysm exclusion?
PURPOSE: To review the anatomic factors crucial to successful endoluminal abdominal aortic aneurysm (AAA) repair and propose an ideal endograft design for AAA exclusion. METHODS AND RESULTS: The anatomic features of critical importance to endovascular AAA exclusion comprise remote arterial access, proximal and distal fixation sites, AAA morphology, and arterial wall pathology. When designing an aortic endograft, the major components to consider are stent selection, graft material, and the delivery system. The ideal endograft design must be sufficiently versatile to treat a broad range of patients. To meet this requirement, the endograft should display a high degree of dimensional adaptability. A modular bifurcated endograft design permits intraoperative customization to tailor the device to each patient's anatomy and pathology. CONCLUSIONS: The modular stent-graft concept addresses many of the important factors in the evolution toward an ideal aortic endograft. Extensive testing will be needed to determine if the bifurcated stent-graft described here is the optimal design for effective AAA exclusion.
Aortic Aneurysm, Abdominal↗