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3.
J Dtsch Dermatol Ges ; 21(10): 1249-1262, 2023 10.
Article in English | MEDLINE | ID: mdl-37845077
4.
Sci Rep ; 9(1): 17873, 2019 Nov 29.
Article in English | MEDLINE | ID: mdl-31784539

ABSTRACT

Fermionization is what happens to the state of strongly interacting repulsive bosons interacting with contact interactions in one spatial dimension. Crystallization is what happens for sufficiently strongly interacting repulsive bosons with dipolar interactions in one spatial dimension. Crystallization and fermionization resemble each other: in both cases - due to their repulsion - the bosons try to minimize their spatial overlap. We trace these two hallmark phases of strongly correlated one-dimensional bosonic systems by exploring their ground state properties using the one- and two-body density matrix. We solve the N-body Schrödinger equation accurately and from first principles using the multiconfigurational time-dependent Hartree for bosons (MCTDHB) and for fermions (MCTDHF) methods. Using the one- and two-body density, fermionization can be distinguished from crystallization in position space. For N interacting bosons, a splitting into an N-fold pattern in the one-body and two-body density is a unique feature of both, fermionization and crystallization. We demonstrate that this splitting is incomplete for fermionized bosons and restricted by the confinement potential. This incomplete splitting is a consequence of the convergence of the energy in the limit of infinite repulsion and is in agreement with complementary results that we obtain for fermions using MCTDHF. For crystalline bosons, in contrast, the splitting is complete: the interaction energy is capable of overcoming the confinement potential. Our results suggest that the spreading of the density as a function of the dipolar interaction strength diverges as a power law. We describe how to distinguish fermionization from crystallization experimentally from measurements of the one- and two-body density.

5.
Ir Med J ; 110(2): 515, 2017 Feb 10.
Article in English | MEDLINE | ID: mdl-28657260

ABSTRACT

Scaphoid fractures are the most common carpal bone fracture. Up to 40% of scaphoid fractures can be missed at initial presentation and investigation. Follow-up plain film radiograph has overall poor sensitivity and reliability. MRI has been shown to have an almost 100% sensitivity and specificity and so is the gold standard in scaphoid fracture diagnosis. Additionally, early specialist involvement is recommended. We proposed that following a designated pathway, there would be no significant increase in MRI requests. Following implementation of a pathway for the management of suspected scaphoid fractures in St James's Hospital in 2012 re-auditing demonstrated that management changed to either MRI directly after initial x-ray (16/145, 11%), MRI after second x-ray (9/28, 32%) or orthopaedic follow-up (19/28, 68%). The number of MRIs requested was consistent with our predictors of demand. Thus, our new protocol maximises diagnostics, cost effectiveness and quality of patient care.


Subject(s)
Emergency Service, Hospital , Fractures, Bone/diagnostic imaging , Magnetic Resonance Imaging/standards , Scaphoid Bone/injuries , Humans , Magnetic Resonance Imaging/statistics & numerical data , Reproducibility of Results , Sensitivity and Specificity , Wrist Injuries/diagnostic imaging
6.
Oncogene ; 36(17): 2394-2404, 2017 04 27.
Article in English | MEDLINE | ID: mdl-27941874

ABSTRACT

Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1 gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1 expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.


Subject(s)
Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Nonheme Iron Proteins/genetics , Proteins/metabolism , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Cell Line, Tumor , Cell Movement , Disease Progression , Humans , Intracellular Signaling Peptides and Proteins , Neoplasm Invasiveness , Promoter Regions, Genetic/genetics , Signal Transduction
7.
Clin Exp Allergy ; 47(3): 331-338, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27928844

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones that regulate glucose metabolism. GLP-1 also has immune modulatory roles. OBJECTIVES: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. METHODS: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects. GLP-1R expression was measured on eosinophils and neutrophils. Subsequently, the asthmatic subjects underwent allergen and diluent inhalation challenges, and GLP-1R expression was measured. Purified eosinophils, collected from mild asthmatic subjects, were stimulated with lipopolysaccharide (LPS) and a GLP-1 analog to evaluate eosinophil cell activation markers CD11b and CD69 and cytokine (IL-4, IL-5, IL-8 and IL-13) production. RESULTS: Glucagon-like peptide-1 receptor is expressed on human eosinophils and neutrophils. Eosinophil, but not neutrophil, expression of GLP-1R is significantly higher in normal controls compared to allergic asthmatics. The expression of GLP-1R did not change on either eosinophils or neutrophils following allergen challenge. A GLP-1 analog significantly decreased the expression of eosinophil-surface activation markers following LPS stimulation and decreased eosinophil production of IL-4, IL-8 and IL-13, but not IL-5. CONCLUSION AND CLINICAL RELEVANCE: Glucagon-like peptide-1 receptor is expressed on human eosinophils and neutrophils. A GLP-1 analog attenuates LPS-stimulated eosinophil activation. GLP-1 agonists may have additional adjunctive indications in treating persons with concomitant type 2 diabetes mellitus and asthma.


Subject(s)
Eosinophils/immunology , Eosinophils/metabolism , Gene Expression , Glucagon-Like Peptide-1 Receptor/genetics , Immunomodulation/genetics , Adult , Allergens/administration & dosage , Allergens/immunology , Asthma/diagnosis , Asthma/genetics , Asthma/immunology , Asthma/metabolism , Bronchial Provocation Tests , Female , Humans , Male , Methacholine Chloride/administration & dosage , Middle Aged , Respiratory Function Tests , Young Adult
8.
Clin Pharmacol Ther ; 99(1): 38-48, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26502193

ABSTRACT

Asthma is characterized by discordant responses among cells of the adaptive and innate immune systems. This interplay involves a complex pattern of cytokine-driven processes resulting in cell migration and recruitment, inflammation, and proliferative states. The significant majority of asthmatic patients respond well to conventional inhaled treatments. However, about 5% of asthmatics have severe refractory asthma and account for 50% of the health expenditure on asthma. Human(ized) monoclonal antibodies (hMabs) targeting inflammatory pathways are promising therapeutic agents in asthma management. The anti-IgE hMab omalizumab was the first biologic treatment approved for the treatment of allergic asthma. Potential future strategies and targets include interleukin (IL)-5, IL-4, and IL-13, anti-TSLP, IL-25, and IL-33. hMabs targeting IL-5 have shown great promise in severe refractory asthma with a persisting eosinophilia, and clinical trials with hMabs against IL-13 and IL4Rα have also shown clinical benefit. Studies of hMabs against other cytokines in severe asthma are under way.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Inflammation Mediators/antagonists & inhibitors , Molecular Targeted Therapy/methods , Humans , Models, Immunological
9.
Chirurg ; 86(7): 687-95, 2015 Jul.
Article in German | MEDLINE | ID: mdl-25487999

ABSTRACT

BACKGROUND: Increasing requirements in quality management are leading to a rising number of certifications in the healthcare system. The certification of an institution should lead to this institution being chosen for treatment. OBJECTIVES: This study was carried out to evaluate this statement for surgical oncology. MATERIAL AND METHODS: A questionnaire was developed with which 100 patients, 40 general practitioners and 20 heads of oncology departments were surveyed with respect to the reasons for choosing a specific institution for oncological surgery. RESULTS: Of the patients 40 % followed the recommendations of their general practitioner while only 6 % considered certification as being relevant although 50 % believed certification was most important for their practitioner when choosing the surgical institution. Personal acquaintances were paramount for the choice of institution for 38.1 % of private practitioners, whereas none of the interviewees claimed that certification had had an influence. Of the heads of department 53.8 % answered that certification was irrelevant when referring a patient to another hospital. CONCLUSION: Despite widespread certification of surgical departments, patients, practitioners and heads of departments still rely on recommendations or personal experiences when choosing an institution for surgical oncology. The return rate of 16.4 % (41 received out of 250 questionnaires sent out) for practitioners shows the lack of interest in certification although 50 % of patients believed that the referral was based on this. Certification in surgical oncology has not yet been able to achieve the desired position as a strong quality factor showing that certification has not fulfilled one of the major goals and only plays an insignificant role in patient recruitment via referrals.


Subject(s)
Certification , General Surgery/education , Licensure, Hospital , Medical Oncology/education , Patient Satisfaction , Referral and Consultation , Specialties, Surgical/education , Total Quality Management , Adult , Aged , Aged, 80 and over , Female , Germany , Humans , Male , Middle Aged , Surveys and Questionnaires
10.
Eur J Surg Oncol ; 40(10): 1307-12, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24713551

ABSTRACT

INTRODUCTION: Expression of cancer testis antigens (CTAs) has been associated with prognosis in gastrointestinal stromal tumors (GIST) and other malignancies. CTAs are currently being investigated for cancer immunotherapy. MATERIALS AND METHODS: We analyzed two CTAs, CT10/MAGE-C2 and GAGE, in 51 GIST by immunohistochemistry and correlated it with established histopathological criteria for malignancy. RESULTS: GAGE expression was found in 6/51 (12%) patients, whereas 5/51 (10%) patients expressed CT10/MAGE-C2. 7/51(14%) patients expressed at least one of both CTAs, in 4/51 (8%) patients both CTAs were positive. High-grade GIST are more likely to express GAGE (p = 0.002) and CT10/MAGE-C2 (p = 0.007) compared to less aggressive tumors. All patients with GAGE or CT10/MAGE-C2 expression had moderate- or high-risk of recurrence according to the established risk criteria. The presence of GAGE correlates with mitotic rate (p = 0.001) and tumor size (p = 0.02), but not with tumor location (p = 0.60). CT10/MAGE-C2 also significantly correlates with mitotic rate (p = 0.004) and tumor size (p = 0.002), whereas no correlation could be found with tumor location (p = 0.36). DISCUSSION: CT10/MAGE-C2 and GAGE should be explored together with other previously described CTAs as targets for immunotherapy of GIST in cases, which are refractory to conventional therapy.


Subject(s)
Antigens, Neoplasm/immunology , Gastrointestinal Neoplasms/immunology , Gastrointestinal Stromal Tumors/immunology , Neoplasm Proteins/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Middle Aged
11.
Respiration ; 81(1): 18-25, 2011.
Article in English | MEDLINE | ID: mdl-20134147

ABSTRACT

BACKGROUND: Arterial blood gases (ABGs) are often sampled incorrectly, leading to a 'mixed' or venous sample. Delays in analysis and air contamination are common. OBJECTIVES: We measured the effects of these errors in patients with chronic obstructive pulmonary disease (COPD) exacerbations and controls. METHODS: Arterial and venous samples were analyzed from 30 patients with COPD exacerbation and 30 controls. Venous samples were analysed immediately and arterial samples separated into non-air-contaminated and air-contaminated specimens and analysed at 0, 30, 60, 90 and 180 min. RESULTS: Mean venous pH was 7.371 and arterial pH was 7.407 (p < 0.0001). There was a correlation between venous and arterial pH (r = 0.5347, p < 0.0001). The regression equation to predict arterial pH was: arterial pH = 4.2289 + 0.43113 · venous pH. There were no clinically significant differences in arterial PO2 associated with analysis delay. A statistically significant decline in pH was detected at 30 min in patients with COPD exacerbation (p = 0.0042) and 90 min in controls (p < 0.0001). A clinically significant decline in pH emerged at 73 min in patients with COPD exacerbation and 87 min in controls. Air contamination was associated with a clinically significant increase in PO2 in all samples, including those that were immediately analyzed. CONCLUSIONS: Arterial and venous pH differ significantly. Venous pH cannot accurately replace arterial pH. Temporal delays in ABG analysis result in a significant decline in measured pH. ABGs should be analysed within 30 min. Air contamination leads to an immediate increase in measured PO2, indicating that air-contaminated ABGs should be discarded.


Subject(s)
Diagnostic Errors/prevention & control , Pulmonary Disease, Chronic Obstructive , Aged , Aged, 80 and over , Air Pollution , Arteries/metabolism , Blood Gas Analysis/standards , Critical Pathways/standards , Disease Progression , Female , Humans , Hydrogen-Ion Concentration , Ireland , Laboratories, Hospital/standards , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Reference Standards , Veins/metabolism
12.
Phys Rev E Stat Nonlin Soft Matter Phys ; 80(4 Pt 2): 046317, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19905446

ABSTRACT

Supersonic flow of a superfluid past a slender impenetrable macroscopic obstacle is studied in the framework of the two-dimensional (2D) defocusing nonlinear Schrödinger (NLS) equation. This problem is of fundamental importance as a dispersive analog of the corresponding classical gas-dynamics problem. Assuming the oncoming flow speed is sufficiently high, we asymptotically reduce the original boundary-value problem for a steady flow past a slender body to the one-dimensional dispersive piston problem described by the nonstationary NLS equation, in which the role of time is played by the stretched x coordinate and the piston motion curve is defined by the spatial body profile. Two steady oblique spatial dispersive shock waves (DSWs) spreading from the pointed ends of the body are generated in both half planes. These are described analytically by constructing appropriate exact solutions of the Whitham modulation equations for the front DSW and by using a generalized Bohr-Sommerfeld quantization rule for the oblique dark soliton fan in the rear DSW. We propose an extension of the traditional modulation description of DSWs to include the linear "ship-wave" pattern forming outside the nonlinear modulation region of the front DSW. Our analytic results are supported by direct 2D unsteady numerical simulations and are relevant to recent experiments on Bose-Einstein condensates freely expanding past obstacles.


Subject(s)
Models, Theoretical , Nonlinear Dynamics , Rheology/methods , Computer Simulation
13.
Ir Med J ; 102(6): 181-4, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19722355

ABSTRACT

We explored the relationship between erythema nodosum (EN) and sex, age, serum angiotensin converting enzyme (ACE), bronchoalveolar lavage lymphocytosis (BAL-I), interstitial granulomas and radiological stage in patients presenting with pulmonary sarcoidosis in Ireland. Sixty-nine patients diagnosed with sarcoidosis between 2003 and 2006 were studied. Forty one patients (59%) were male. Sixteen patients (23%) presented with EN. Forty one patients of 65 (63%) had transbronchial biopsies demonstrating non-caseating granulomas. Patients with sarcoidosis presenting with EN were more likely to be female (p=0.042), younger (p=0.012) and have earlier stage pulmonary disease (p=0.02). There were no correlations between serum ACE, interstitial granulomas and disease stage. BAL-I did however predict increasing disease radiological stage (p=0.042). In this study, one quarter of patients with sarcoidosis presented with EN among their presenting features. These patients were more likely to be young females with early stage radiological disease.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Erythema Nodosum/diagnostic imaging , Lymphocytosis/diagnostic imaging , Peptidyl-Dipeptidase A/blood , Sarcoidosis, Pulmonary/diagnostic imaging , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/cytology , Erythema Nodosum/epidemiology , Female , Granuloma/epidemiology , Granuloma/pathology , Humans , Ireland/epidemiology , Lymphocytosis/epidemiology , Male , Middle Aged , Radiography , Retrospective Studies , Risk Factors , Sarcoidosis, Pulmonary/epidemiology , Sarcoidosis, Pulmonary/pathology , Statistics as Topic , Young Adult
14.
Phys Rev Lett ; 97(18): 180405, 2006 Nov 03.
Article in English | MEDLINE | ID: mdl-17155522

ABSTRACT

In the framework of the Gross-Pitaevskii mean field approach, it is shown that the supersonic flow of a Bose-Einstein condensate can support a new type of pattern--an oblique dark soliton. The corresponding exact solution of the Gross-Pitaevskii equation is obtained. It is demonstrated by numerical simulations that oblique solitons can be generated by an obstacle inserted into the flow.

15.
Diabet Med ; 19(6): 522-5, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12109439

ABSTRACT

AIMS: To provide age-gender standardized incidence rate, temporal trend and seasonal variation of Type 1 diabetes in Kuwaiti children aged < or = 14 years. METHODS: Data were prospectively collected over a period of 6 years (1992-1997) according to the DiaMond Project protocol using the capture-recapture method of ascertainment. RESULTS: Data ascertainment varied between 90% and 96%. The incidence rate of Type 1 diabetes was 20.1 per 100,000 children 0-14 years (95% confidence interval (CI) 18.0-22.1); age-standardized incidence rate 20.9 (95% CI 18.8-23.0). The incidence rate among boys, 21.1 per 100,000 (95% CI 18.1-24.1) was slightly higher than that among girls, 19.0 per 100,000 (95% CI 16.1-21.8). The age-standardized incidence rate was 21.9 (95% CI 18.9-24.8) in boys, and 19.9 (95 CI 17.1-22.8) in girls. Incidence rates increased with age in both sexes (boys chi(2) for linear trend = 13.5, P < 0.001; and for girls chi(2) = 27.8, P < 0.0001). There was a significant trend towards increase in overall incidence during the 6-year period (chi(2) = 6.210, P = 0.013), and in age group 5-9 (chi(2) = 10.8, P = 0.001). Seasonality was demonstrated overall, in boys and girls (P < 0.001). CONCLUSION: The incidence of Type 1 diabetes in Kuwait is high compared with the neighbouring Arab countries, and it appears to be increasing as in many European populations.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Adolescent , Age Distribution , Child , Child, Preschool , Confidence Intervals , Female , Humans , Incidence , Infant , Kuwait/epidemiology , Male , Prospective Studies , Reproducibility of Results , Seasons , Time Factors
16.
Acta Microbiol Immunol Hung ; 48(1): 39-52, 2001.
Article in English | MEDLINE | ID: mdl-11233699

ABSTRACT

Twenty-four different strains of Streptomyces spp. isolated from Egyptian soil were tested for their ability to produce extracellular xylanases. Of all these isolates a Streptomyces sp. that had the highest potential for xylanolytic activity was chosen. From various morphological, physiological and antagonistic properties, this isolate was found to belong to Streptomyces lividans. Factors affecting xylanase production by this organism in a basal salt medium containing purified sugar-cane bagasse xylan as a sole carbon source were examined. A noticeable increase in enzyme activity was observed in the presence of peptone or soyabean meal. However, a slight increase was noticed with ammonium sulphate. Optimum production for xylanase was achieved after five days incubation on a rotary shaker (180 rpm) at 30 degrees C. The initial pH values were around neutrality. In addition, this organism has high potential for xylanolytic activity when grown on lignocellulosic wastes including corn cobs, wheat bran, peanut shells, sawdust, wheat straw and sugar-cane-bagasse. Partial purification of the enzyme in the culture supernatant was achieved by salting out at 50-80% ammonium sulphate saturation with a purification of 9.03-fold and 57.9% recovery.


Subject(s)
Soil Microbiology , Streptomyces/enzymology , Xylans/metabolism , Xylosidases/metabolism , Agriculture , Carbohydrate Metabolism , Culture Media , Enzyme Induction , Streptomyces/classification , Streptomyces/cytology , Streptomyces/isolation & purification , Waste Products , Xylan Endo-1,3-beta-Xylosidase , Xylosidases/isolation & purification
17.
Diagn Microbiol Infect Dis ; 36(3): 169-73, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10729659

ABSTRACT

Although numerous studies have evaluated the sensitivity and specificity of different assays for Clostridium difficile toxin, none has evaluated how physicians utilize these tests or respond to test results. Therefore, we assessed patient characteristics, clinical findings, and physician responses to positive and negative assay results at two university-affiliated hospitals, one of which used a cell cytotoxicity assay to test for C. difficile toxin and the other of which used an enzyme immunoassay. Two hundred one patient samples at Hospital A and 199 samples at Hospital B were assessed. Positive toxin assays were more frequent at Hospital A than at Hospital B (p < 0.001), at least in part due to the fact that patients tested at Hospital A were more likely to have fever (p < 0.001), an abnormal abdominal exam (p < 0.001), an abnormal leukocyte count (p < 0.001), and a history of prior antibiotic use (p < 0.001). Empiric therapy for C. difficile before results of the toxin assay was more common (p < 0.001) at Hospital A (83/201, 41. 3%) than at Hospital B (25/199, 12.5%). Once empiric therapy was started, most physicians continued therapy despite negative test results (Hospital A, 76%; Hospital B, 69%). Patients who were treated empirically were more likely than patients not treated empirically to have positive toxin assay results and to have fever (p < 0.001), an abnormal abdominal exam (p = 0.003), or an abnormal leukocyte count (p < 0.05). Physicians seldom ordered repeat toxin assays (Hospital A, 14%; Hospital B, 10%) if the initial assay result was negative. In logistic regression analysis, predictors of a positive toxin assay were prior antibiotic therapy, an abnormal abdominal exam, residence at Hospital A, and age >/= 60 years. Predictors of empiric therapy were residence at Hospital A and prior antibiotic therapy. Because physicians electing to empirically treat inpatients with diarrhea rarely alter therapy based on C. difficile toxin assay results, a more cost-effective management strategy may be not to obtain a toxin assay at all in such situations. Testing should be limited to patients who have received antibiotics within the prior month and who have significant diarrhea and/or abdominal pain.


Subject(s)
Bacterial Toxins/analysis , Clostridioides difficile/growth & development , Diarrhea/microbiology , Practice Patterns, Physicians' , Bacteriological Techniques , Cross Infection/microbiology , Diarrhea/therapy , Female , Hospitalization , Humans , Immunoenzyme Techniques , Male
18.
Article in English | MEDLINE | ID: mdl-11970045

ABSTRACT

In the present work, we improve a numerical method, developed to solve the Gross-Pitaevkii nonlinear Schrödinger equation. A particular scaling is used in the equation, which permits us to evaluate the wave-function normalization after the numerical solution. We have a two-point boundary value problem, where the second point is taken at infinity. The differential equation is solved using the shooting method and Runge-Kutta integration method, requiring that the asymptotic constants, for the function and its derivative, be equal for large distances. In order to obtain fast convergence, the secant method is used.

19.
J Heart Lung Transplant ; 17(9): 881-7, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9773860

ABSTRACT

BACKGROUND: Despite the advances made in immunosuppression therapy, episodes of acute cellular rejection may affect graft function and survival. We investigated the role of RANTES in cellular recruitment and in cardiac allograft rejection. METHODS: Endomyocardial biopsies (n = 65) from 30 patients were taken at various times after transplantation. In 4 subjects who died of acute cellular rejection, the profile of RANTES expression was monitored in all biopsy specimens and in postmortem tissue. Myocardial tissue from 10 other transplants was also analyzed. Sections were stained with an anti-human RANTES antibody with the streptavidin-biotin technique. RANTES-positive cells were related to macrophage, CD45RO "memory" T-cell, and eosinophil infiltration. RESULTS: RANTES-positive cells were identified within the cellular infiltrate in 95% of biopsies with moderate/severe rejection and 28% with mild rejection. RANTES-positive, CD45RO-positive, and macrophage cell numbers were higher in subjects who died of acute cellular rejection than of other causes. A highly significant difference in RANTES-positive cell number was observed between moderate/severe, mild, and nonrejection groups (p = .0001) and correlated significantly with macrophage number in both right and left ventricles (r = .693, p < .01; r = .599, p < .05, respectively) and with the number of "memory" T cells (r = .829, p < .001; r = .779, p < .01, respectively). CONCLUSIONS: These findings suggest that local release of RANTES is important in the recruitment of both macrophages and CD45RO T cells in cardiac allograft rejection. RANTES may be an important chemokine to target for therapeutic intervention in heart rejection.


Subject(s)
Chemokine CCL5/physiology , Graft Rejection/immunology , Heart Transplantation , Leukocyte Common Antigens/analysis , Macrophages/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Chemokine CCL5/analysis , Female , Humans , Immunohistochemistry , Immunologic Memory , Macrophages/chemistry , Male , Middle Aged , T-Lymphocytes/chemistry
20.
J Vet Pharmacol Ther ; 15(2): 133-42, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1433475

ABSTRACT

The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady-state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half-life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h.


Subject(s)
Amikacin/pharmacokinetics , Chickens/metabolism , Muscles/metabolism , Absorption , Amikacin/administration & dosage , Animals , Biological Availability , Female , Fluorescence Polarization , Half-Life , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary
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