Clinical Applicability (clinical + applicability)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Clinical applications of laser scanning cytometry

CYTOMETRY, Issue 3 2002
Attila Tárnok
Abstract This study reviews existing and potential clinical applications of laser scanning cytometry (LSC) and outlines possible future developments. LSC provides a technology for solid phase cytometry. Fluorochrome-labeled specimens are immobilized on microscopic slides that are placed on a conventional epifluorescence microscope and analyzed by one or two lasers. Data comparable to flow cytometry are generated. In addition, the position of each event is recorded, a feature that allows relocalization and visualization of each measured event. The major advantage of LSC compared with other cytometric methods is the combination of two features: (a) the minimal clinical sample volume needed and (b) the connection of fluorescence data and morphological information for the measured event. Since the introduction of LSC, numerous methods have been established for the analysis of cells, cellular compartments, and tissues. Although most cytometric methods use only two or three colors, the characterization of specimens with up to five fluorochromes is possible. Most clinical applications have been designed to determine ploidy and immunophenotype; other applications include analyses of tissue biopsies and sections, fluorescence in situ hybridization, and the combination of vital and nonvital information on a single-cell basis. With the currently available assays, LSC has proven its wide spectrum of clinical applicability in slide-based cytometry and can be introduced as a standard technology in multiple clinical settings. Cytometry (Clin. Cytometry) 50:133,143, 2002. © 2002 Wiley-Liss, Inc. [source]

Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cells

Danielle E. Westfall M.D.
Abstract There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005,2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 ± 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]

Proximal Isovelocity Surface Area (PISA) in the Evaluation of Fixed Membranous Subaortic Stenosis

Gregory M. Goodkin M.D.
The evaluation of the severity of subaortic stenosis is usually expressed by the magnitude of the subvalvular gradient. Calculation of the membrane orifice area noninvasively is difficult by the standard means. We present a patient in whom the area was calculated using the proximal isovelocity surface area (PISA) method. This method should have clinical applicability because it is not flow dependent and can be used in patients with normal, reduced, or increased stroke volume. [source]

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5-fluorouracil resistance

Young-Kyoung Shin
Abstract 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, resistance to this drug is a major obstacle in CRC chemotherapy. Accurate prediction of response to 5-FU would avoid unnecessary chemotherapy and allow the selection of other effective drugs. To identify a candidate predictor of 5-FU resistance, we isolated secreted proteins that were up- or downregulated in a 5-FU-resistant cancer cell line, compared with the parent cell line (SNU-C4), using a stable isotope-coded labeling protocol. For validating the clinical applicability of this method, levels of the identified proteins were determined in the sera of 46 patients treated with 5-FU. In total, 238 proteins with molecular weights ranging from 50 to 75,kDa were identified. Among these, 45 and 35 secreted proteins were up- and downregulated in the 5-FU-resistant cell line, respectively. We observed significant upregulation of glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1. In particular, the level of PK-M2, a key enzyme in the glycolytic pathway, showed an increasing tendency in both sera and tissues from CRC patients displaying no response to 5-FU-based chemotherapy (progressive and stable disease cases), compared with that in complete or partial responders to 5-FU-based chemotherapy; however, it did not reach the statistical significance. In conclusion, increasing pattern of PK-M2 observed with 5-FU resistance induced in vitro and in sera and tissues from CRC patients displaying poor response to 5-FU-based chemotherapy suggest the relevance of dysregulated glycolysis and 5-FU-resistant CRC. [source]

Assessment of tracheal temperature and humidity in laryngectomized individuals and the influence of a heat and moisture exchanger on tracheal climate

J. Karel Zuur MD
Abstract Background The beneficial function of heat and moisture exchangers (HMEs) is undisputed, but knowledge of their effects on intra-airway temperature and humidity is scarce. The aim of this study was to evaluate the clinical applicability of a new airway climate explorer (ACE) and to assess the HME's influence on tracheal climate. Methods Intratracheal temperature and humidity were measured with and without HME in 10 laryngectomized patients. Results An HME causes the intratracheal mean humidity minima to increase with 3.2 mg H2O/L (95% CI: 1.5,4.8 mg H2O/L; p <.001), from 21.4 to 24.6 mg H2O/L, and the mean temperature minima to decrease with 1.6°C (95% CI: 0.9,2.4°C; p <.001) from 28.5°C to 26.9°C. Relative humidity values suggest that the tested HME keeps inspired air (nearly) fully saturated during the full course of inspiration. Conclusion Assessment of intratracheal temperature and humidity, and evaluation of HME effectiveness is feasible with the ACE. The tested HME significantly increases the intratracheal humidity, but decreases the intratracheal temperature. Relative humidity calculations suggest that increasing the thermal capacity of this rehabilitation device can further increase the heat and moisture exchange efficiency. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source]

Construction and validation of a patient- and user-friendly nursing home version of the Geriatric Depression Scale,

K. Jongenelis
Abstract Objective To construct a patient- and user-friendly shortened version of the Geriatric Depression Scale (GDS) that is especially suitable for nursing home patients. Methods The study was carried out on two different data bases including 23 Dutch nursing homes. Data on the GDS (n,=,410), the Mini Mental State Examination (n,=,410) and a diagnostic interview (SCAN; n,=,333), were collected by trained clinicians. Firstly, the items of the GDS-15 were judged on their clinical applicability by three clinical experts. Subsequently, items that were identified as unsuitable were removed using the data of the Assess project (n,=,77), and internal consistency was calculated. Secondly, with respect to criterion validity (sensitivity, specitivity, area under ROC and positive and negative predictive values), the newly constructed shortened GDS was validated in the AGED data set (n,=,333), using DSM-IV diagnosis for depression as measured by the SCAN as ,gold standard'. Results The eight-item GDS that resulted from stage 1 showed good internal consistency in both the Assess data set (,,=,0.86) and the AGED dataset (,,=,0.80). In the AGED dataset, high sensitivity rates of 96.3% for major depression and 83.0% for minor depression were found, with a specificity rate of 71.7% at a cut-off point of 2/3. Conclusion The GDS-8 has good psychometric properties. Given that the GDS-8 is less burdening for the patient, more comfortable to use and less time consuming, it may be a more feasible screening test for the frail nursing home population. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro

Sanna-Mari Niemelä
Abstract Antibiotic coating systems have been successfully used to prevent bacterial attachment and biofilm formation. Our purpose was to evaluate whether bioabsorbable polylactide-co-glycolide (PLGA) 80/20 on its own, and PLGA together with ciprofloxacin (PLGA+C) have any advantages over titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. Cylindrical specimens of titanium, PLGA, and PLGA+C in triplicate were examined for S. epidermidis ATCC 35989 attachment and biofilm formation after incubation with a bacterial suspension of about 105 cfu/mL for 1, 3, 7, 14, and 21 days, using scanning electron microscopy. Growth inhibition properties of PLGA and PLGA+C cylinders were tested on agar plates. On days 1, 3, and 21, no bacterial attachment was seen in 19.5, 9.2, and 41.4% of the titanium specimens; in 18.4, 28.7, and 34.5% of the PLGA specimens; and in 57.5, 62.1, and 57.5% of the PLGA+C specimens, respectively. During the whole study period, no biofilm was observed on 74,93% of the titanium specimens, 58,78% of the PLGA specimens, and 93,100% of the PLGA+C specimens. PLGA+C showed clear bacterial growth inhibition on agar plates, while PLGA and titanium did not show any inhibition. PLGA+C bioabsorbable material was superior to titanium in preventing bacterial attachment and biofilm formation and may have clinical applicability, for example, in prevention of infection in trauma surgery or in the treatment of chronic osteomyelitis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source]

Increased Levels of Tissue Plasminogen Activator Antigen and Factor VIII Activity in Nonvalvular Atrial Fibrillation: Relation to Predictors of Thromboembolism

Atrial Fibrillation and Hypercoagulability.Introduction: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. Methods and Results: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, age, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. Conclusion: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation. [source]

Loving-kindness meditation to enhance recovery from negative symptoms of schizophrenia

David P. Johnson
Abstract In this article, we describe the clinical applicability of loving-kindness meditation (LKM) to individuals suffering from schizophrenia-spectrum disorders with persistent negative symptoms. LKM may have potential for reducing negative symptoms such as anhedonia, avolition, and asociality while enhancing factors consistent with psychological recovery such as hope and purpose in life. Case studies will illustrate how to conduct this group treatment with clients with negative symptoms, the potential benefits to the client, and difficulties that may arise. Although LKM requires further empirical support, it promises to be an important intervention since there are few treatments for clients afflicted with negative symptoms. © 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65: 1,11, 2009. [source]

Repair of porcine articular cartilage defect with a biphasic osteochondral composite,

Ching-Chuan Jiang
Abstract Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with ,-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress,relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277,1290, 2007 [source]

Current opportunities and challenges in skeletal muscle tissue engineering

Merel Koning
Abstract The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high proneness to muscular differentiation, in particular exhibiting the same characteristics and function as its donor muscle. This suggests that it is important to use an appropriate progenitor cell, especially in TE facial muscles, which have a exceptional anatomical and fibre composition compared to other skeletal muscle. Muscle TE requires an instructive scaffold for structural support and to regulate the proliferation and differentiation of muscle progenitor cells. Current literature suggests that optimal scaffolding could comprise of a fibrin gel and cultured monolayers of muscle satellite cells obtained through the cell sheet technique. Tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen, carbon dioxide, nutrients and waste products. Finally, functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural cells. To reach this, it seems important to apply optimal electrical, chemotropic and mechanical stimulation during engineering and discover other factors that influence its formation. Thus, in addition to approaches for myogenesis, we discuss the current status of strategies for angiogenesis and neurogenesis of TE muscle constructs and the significance for future clinical use. Copyright © 2009 John Wiley & Sons, Ltd. [source]

In-vivo diagnosis and non-inasive monitoring of Imiquimod 5% cream for non-melanoma skin cancer using confocal laser scanning microscopy

S. Dietterle
Abstract Basal cell carcinoma (BCC) is the most common cutaneous malignancy with increasing incidence rates worldwide. A number of established treatments are available, including surgical excision. The emergence of new non-invasive treatment modalities has prompted the development of non-invasive optical devices for therapeutic monitoring and evaluating treatment efficacy. This study was aimed to evaluate the clinical applicability of a fluorescence confocal laser scanning microscope (CFLSM) for non-invasive therapeutic monitoring of basal cell carcinoma treated with Imiquimod (Aldara®) as topical immune-response modifier. Eight participants with a diagnosis of basal cell carcinoma (BCC) were enrolled in this investigation. Sequential evaluation during treatment with Imiquimod showed progressive normalization of the confocal histomorphologic parameters in correlation with normal skin. Confocal laser scanning microscopy was able to identify characteristic features of BCC and allowed the visualization of therapeutic effects over time. Thus our results indicate the clinical applicability of CFLSM imaging to evaluate treatment efficacy in vivo and non-invasively. (© 2008 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) [source]

Reliability of a new ultrasonic cardiac output monitor in recipients of living donor liver transplantation,,§¶

Bai-Chuan Su
The ultrasonic cardiac output monitor (USCOM) is a new Doppler device for noninvasive hemodynamic monitoring. The aim of this prospective nonrandomized study was to test the feasibility, perioperative reliability, and clinical applicability of using USCOM as an alternative to pulmonary artery catheterization in recipients of living donor liver transplantation. Thirteen patients scheduled to receive living donor liver transplants were initially recruited. Three were subsequently excluded prior to the commencement of surgery because of technical difficulties in obtaining diagnostic-quality images with USCOM. Ten patients proceeded to be studied. Cardiac output measurements by thermodilution and USCOM were compared at 30-minute intervals throughout the procedure and at 10 specific procedural reference points during the surgery when hemodynamic changes were most likely to be observed. The data were analyzed with Lin's concordance coefficient and Bland-Altman analysis. Two hundred ninety paired cardiac output values were obtained from the 10 patients. The concordance between both methods was excellent in 8 patients and satisfactory in 2. Bland-Altman analysis of all data produced a mean bias of , 0.02 L/minute for USCOM, and the 95% limits of agreement were ,1.06 to +1.10 L/minute. Further analysis of the 10 reference time points showed minimal bias and high levels of agreement between the methods. We conclude that USCOM provides an accurate and noninvasive method for cardiac output measurement during liver transplantation. It may therefore represent an alternative to pulmonary artery catheter placement with consequent reduction in patient's risk and morbidity associated with catheterization. Liver Transpl 14:1029,1037, 2008. © 2008 AASLD. [source]

Development and validation of new model for microvascular transplantation of epiphyseal plate allografts with minimal adjoining epiphyseal and metaphyseal bone

MICROSURGERY, Issue 2 2003
M.Sc., Peter W. Bray M.D.
A model for the free allograft microvascular transplantation of rabbit proximal tibial epiphyseal plate allografts was developed, validated, and tested in an in vivo animal model. Transplants contained the minimum amount of adjacent epiphyseal and metaphyseal bone compatible with preservation of the epiphyseal-plate vascular supply, as determined by corrosion casting. Perfusion to this graft was evaluated quantitatively using radioactive microspheres, and qualitatively using India-ink injection. Female New Zealand White rabbits at 12 weeks of age were utilized. Vascularized transplantation of epiphyseal plate allografts was performed either into a defect of matched size in the iliac crest or into a soft-tissue pocket without bone contact. Cyclosporine A immunosuppression (CSA) was administered daily for 6 weeks. Two control groups underwent identical surgical procedures, but had no postoperative immunosuppression. Epiphyseal plates both with and without bone contact, in rabbits immunosuppressed postoperatively with CSA, demonstrated longitudinal growth and preserved viability as determined by positive bromodeoxyuridine uptake. Control epiphyseal plates transferred without postoperative immunosuppression were uniformly nonviable. This new model has value as a basis for further studies into the clinical applicability of isolated epiphyseal-plate transplants. © 2003 Wiley-Liss, Inc. MICROSURGERY 23:153,163 2003 [source]

Content validity and clinical applicability of the Irena Daily Activity assessment measuring occupational performance in adults with developmental disability

Irena Dychawy-Rosner MSc
Abstract The purpose of this study was to investigate the validity of the Irena Daily Activity (IDA) assessment which measures occupational performance in adults with developmental disabilities. The instrument's content validity was investigated by elucidating its general appropriateness, its clinical applicability and the feasibility of the measurement procedure. Data were collected from a multidisciplinary panel of clinical experts working in day activity centres. Each expert independently judged and reviewed the IDA instrument's content validity. The results show that the content validity index (CVI) values ranged from 0.8 to 1.0 for the instrument's general appropriateness and clinical applicability, and from 0.7 to 1.0 with respect to the significance of the IDA domains' clinical applicability. The applicability of the IDA items were judged as satisfactory (CVI , 80) with respect to their importance for planning treatment and intervention. The feasibility of the measurement procedure was estimated as satisfactory in relation to the items (CVI , 0.70) and satisfactory with respect to the time needed and material used, with CVI values ranging from 0.8 to 1.0. The results of this study support the use of the IDA as a feasible and time-efficient assessment that provides insights regarding the occupational performance of adults with developmental disabilities. A limitation of this study was that it could not illuminate all-important aspects of validity. In conclusion, the IDA has the potential to become a reliable and valid clinical assessment, but additional research on psychometric properties is still needed. Copyright © 2003 Whurr Publishers Ltd. [source]

Normal ranges of angiogenesis regulatory proteins in human platelets,

Jon E. Peterson
Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/106 platelets); PDGF (23 ± 6 pg/106); PF4 (12 ± 5 ng/106); TSP-1 (31 ± 12 ng/106); bFGF (0.44 ± 0.15 pg/106); and endostatin (5.6 ± 3.0 pg/106). There was an excellent correlation (R2 = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF-4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]

Synthetic Tannins in Dermatology,A Therapeutic Option in a Variety of Pediatric Dermatoses

Regina Fölster-Holst M.D.
The therapeutic effects of synthetic tannins are based on their tanning action as well as on their antimicrobial, anti-inflammatory, and antipruritic effects. In terms of pharmacology and clinical applicability, synthetic tannins are particularly versatile substances. They have also been used as steroid-free, anti-inflammatory treatment alternatives, especially in pediatric dermatoses. Systemic absorption is not to be expected. Because of their high safety profile and good tolerance, they are appropriate for the treatment of all age groups. Thus, synthetic tannins can be safely used for infants and children and also during pregnancy and lactation. [source]

Reproducibility of multiple breath washout indices in the unsedated preterm neonate,

Sanjay Sinhal FRACP
Abstract Multiple breath inert gas washout (MBW) is gaining popularity for measurements of resting lung volume and ventilation inhomogeneity. Test reproducibility is an important determinant of the clinical applicability of diagnostic tests. The between-test reproducibility of variables derived from MBW tests in newborn infants is unknown. We aimed to determine the within-test repeatability and short-term between-test reproducibility of MBW variables in unsedated preterm infants. We hypothesized that measurements obtained within a 3-day interval in clinically stable preterm infants would be reproducible and suitable for use as an objective clinical outcome measurement. In this cross-sectional observational study, clinically stable hospitalized preterm infants whose parents had given informed consent for MBW studies were tested twice within 72,hr during quiet, unsedated sleep. Functional residual capacity (FRC), lung clearance index (LCI), and the first and second to zeroeth moment ratios (M1:M0; M2:M0) were computed from MBW traces obtained using a mainstream ultrasonic flowmeter and 4% sulphur hexafluoride (MBWSF6). Within-test repeatability and between-test reproducibility were determined. Within-test repeatability (expressed as a coefficient of variability (Cv)) for differences between two and four replicate measurements on the same test occasion, were 9.3% (FRC), 9.0% (LCI), 7.6% (M1:M0), and 15.6% (M2:M0), respectively. The within-test Cv's were not statistically different to the between-tests Cv's, which were 7.7% (FRC), 10.3% (LCI), 6.1% (M1:M0), and 13.0% (M2:M0), respectively. Among unsedated preterm infants, between-test reproducibility over a 3-day interval was similar to within-test repeatability. The wide limits of agreement may limit the application of these measures to detect a clinically significant change in condition in small preterm infants. Pediatr Pulmonol. 2010; 45:62,70. © 2009 Wiley-Liss, Inc. [source]

Simultaneous determination of endogenous deoxynucleotides and phosphorylated nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cells using ion-pair liquid chromatography coupled to mass spectrometry

Leon Coulier
Abstract Nucleoside reverse transcriptase inhibitors (NRTIs) are activated intracellularly to their triphosphate (TP) form, which compete with endogenous deoxynucleotide-triphosphates (dNTP) as substrate for HIV reverse transcriptase. The activity of NRTIs is thus described by the NRTI-TP-to-dNTP ratio in relevant cell types. Therefore, we developed an ion-pair (IP) LC-MS method for the simultaneous analysis of the mono-, di-, and TP forms of NRTIs and endogenous deoxynucleosides in peripheral blood mononuclear cells (PBMC). The IP-LC method was applied on an IT mass spectrometer using the MS-mode as well as on a triple quadrupole mass spectrometer using the MS/MS mode. The MS/MS approach on the triple quadrupole mass spectrometer demonstrated the best clinical applicability due to its higher sensitivity. The LOD (minimum amount on column) were 25,fmol for the TP forms of zidovudine, lamivudine, and stavudine, as well as for their endogenous dNTP counterparts. The linearity (R2) of the calibration curves were>0.99. The obtained LOD readily allow for clinical applications using just one million PBMC obtained from HIV-infected patients under therapy. [source]

Infusion of Mesenchymal Stem Cells and Rapamycin Synergize to Attenuate Alloimmune Responses and Promote Cardiac Allograft Tolerance

W. Ge
The inherent immunosuppressive properties and low immunogenicity of mesenchymal stems cells (MSCs) suggested their therapeutic potential in transplantation. We investigated whether MSCs could prolong allograft survival. Treatment involving infusion of MSCs into BALB/c recipients 24 hours after receiving a heart allograft from a C57BL/6 donor significantly abated rejection and doubled graft mean survival time compared to untreated recipients. Furthermore, combination therapy of MSCs and low-dose Rapamycin (Rapa) achieved long-term heart graft survival (>100 days) with normal histology. The treated recipients readily accepted donor skin grafts but rejected third-party skin grafts, indicating the establishment of tolerance. Tolerant recipients exhibited neither intragraft nor circulating antidonor antibodies, but demonstrated significantly high frequencies of both tolerogenic dendritic cells (Tol-DCs) and CD4+CD25+Foxp3+T cells in the spleens. Infusion of GFP+C57BL/6-MSCs in combination with Rapa revealed that the GFP-MSCs accumulated in the lymphoid organs and grafts of tolerant recipients. Thus, engraftment of infused MSCs within the recipient's lymphoid organs and allograft appeared to be instrumental in the induction of allograft-specific tolerance when administered in combination with a subtherapeutic dose of Rapamycin. This study supports the clinical applicability of MSCs in transplantation. [source]

Nonlinear Analysis of Heart Rate Variability: Fractal and Complexity Measures of Heart Rate Behavior

Juha S. Perkiömäki M.D.
Many new methods of analyzing heart rate (HR) variability have been developed to describe the features in HR behavior that cannot be detected by traditional time- and frequency-domain methods. Some of the new methods, such as analysis of fractal correlation properties and complexity of HR dynamics, have provided clinically useful information in various patient populations. Importantly, some fractal analysis methods are better risk predictors of mortality than traditional HR variability measures, and analysis of complexity of HR dynamics has been shown to predict the spontaneous onset of atrial fibrillation. New analysis methods based on nonlinear dynamics are a promising tool for better understanding of normal and abnormal HR behavior. More work will be needed to establish the clinical applicability of traditional and new analysis methods of HR variability. [source]

Amphoteric liposomes enable systemic antigen-presenting cell,directed delivery of CD40 antisense and are therapeutically effective in experimental arthritis

Evangelos Andreakos
Objective Mediation of RNA interference by oligonucleotides constitutes a powerful approach for the silencing of genes involved in the pathogenesis of inflammatory disease, but in vivo application of this technique requires effective delivery to immune cells and/or sites of inflammation. The aim of the present study was to develop a new carrier system to mediate systemic administration of oligonucleotides to rheumatoid arthritis (RA) joints, and to develop an antisense oligonucleotide (ASO),based approach to interfere with CD40,CD154 interactions in an experimental model of RA. Methods A novel liposomal carrier with amphoteric properties, termed Nov038, was developed and assessed for its ability to systemically deliver an ASO directed against CD40 (CD40-ASO). Male DBA/1 mice with collagen-induced arthritis were treated with Nov038-encapsulated CD40-ASO, and the effects of treatment on various parameters of disease activity, including clinical score, paw swelling, lymph node responses, and inflammatory cytokine production in the joints, were assessed. Results Nov038 was well tolerated, devoid of immune-stimulatory effects, and efficacious in mediating systemic oligonucleotide delivery to sites of inflammation. In mice with collagen-induced arthritis, Nov038 enabled the therapeutic administration of CD40-ASO and improved established disease, while unassisted CD40-ASO was ineffective, and anti,tumor necrosis factor , (anti-TNF,) treatment was less effective in this model. Nov038/CD40-ASO efficacy was attributed to its tropism for monocyte/macrophages and myeloid dendritic cells (DCs), resulting in rapid down-regulation of CD40, inhibition of DC antigen presentation, and reduction in collagen-specific T cell responses, as well as decreased levels of TNF,, interleukin-6 (IL-6), and IL-17 in arthritic joints. Conclusion Amphoteric liposomes represent a novel carrier concept for systemic and antigen-presenting cell,targeted oligonucleotide delivery with clinical applicability and numerous potential applications, including target validation in vivo and inflammatory disease therapeutics. Moreover, Nov038/CD40-ASO constitutes a potent alternative to monoclonal antibody,based approaches for interfering with CD40,CD40L interactions. [source]

Injectable calcium phosphate cement as a filler for bone defects around oral implants: an experimental study in goats

Luca Comuzzi
Abstract: The aim of this study was to evaluate the clinical applicability and biological behavior of a newly developed injectable calcium phosphate (Ca-P) cement as bone filler for gaps around oral implants. Twenty-four step-like implants, creating gaps of 1 and 2 mm, were inserted into the trabecular bone of the medial femoral condyles of six goats. Four different situations were tested: (1) implant + gaps; (2) implant + gaps, but covered with a polylactic acid membrane; (3) implant + gaps that were filled with Ca-P cement; and (4) implant + gaps that were filled with Ca-P cement and covered with a membrane. All implants were left in place for 12 weeks. Histological and quantitative histomorphometrical measurements demonstrated that implants + gaps had generally poor bone contact at the implant base. Furthermore, fibrous encapsulation was observed in the gap part. In contrast, the presence of a membrane promoted bone ingrowth into the gap and also the bone contact at the implant base. Injection of Ca-P cement resulted in an almost complete filling of the gaps around the implant. The cement surface was completely covered by bone. Active resorption and remodeling of cement particles was observed, suggesting a pattern of slow resorption associated with full replacement with newly formed bone. Additional use of a membrane did not result in adjunctive benefits. Bone-to-implant contact at the implant base was comparable with the implants provided only with a membrane. In conclusion, the Ca-P cement used here showed excellent clinical handling properties combined with a superior bone behavior. On the other hand, the degradation rate of the material was still very slow. This current characteristic can hamper the final clinical applicability of the material as gap filler for periimplant or periodontal defects. Résumé Le but de l'étude présente a été d'évaluer l'application clinique et le comportement biologique d'un nouveau ciment de calcium de phosphate injectable (Ca-P) comme comblement osseux pour les cavités autour des implantes dentaires. Vingt-quatre implants créant des cavités de 1 et 2 mm ont été insérés dans l'os trabéculaire des condyles fémoraux moyens de six chèvres. Quatre situations différentes ont été testées: 1) implant + cavités; 2) implant = cavités recouvertes par une membrane en acide polylactique, 3) implant + cavités comblées par le ciment Ca-P et 4) implant + cavités comblées par le ciment Ca-P et recouvertes par une membrane. Tous les implants ont été laissés in situ pendant douze semaines. Les mesures histologiques et quantitatives histomorphométriques ont démontré que les implants + cavités avaient généralement un contact osseux pauvre au niveau de la base implantaire. De plus, une encapsulation fibreuse était observée dans la partie cavité. Par contre, la présence d'une membrane favorisait la croissance osseuse dans la cavité ainsi que le contact osseux à la base de l'implant. L'injection du cément Ca-P résultait en une réparation quasi complète des cavités autour de l'implant. La surface cémentaire était complètement recouverte d'os. La résorption active et le remodelage des particules de cément étaient observés, ce qui suggérait un système de résorption lente associéà un remplacement complet par de l'os néóformé. L'usage additionnel d'une membrane ne s'accompagnait pas de bénéfice supplémentaire. Le contact os/implant à la base de l'implant était comparable à celui des implants installés seulement avec une membrane. En conclusion, le ciment Ca-P possèdait des propriétés cliniques excellentes combinées à un comportement osseux supérieur. Par contre le taux de dégradation du matériel était toujours très lent. Cette caractéristique pourrait gêner l'application clinique finale de ce matériel en tant que comblement des cavités autour des implants ou dans les lésions parodontales. Zusammenfassung Das Ziel dieser Studie war es, die klinische Anwendbarkeit und das biologische Verhalten eines neu entwickelten injizierbaren Kalziumphosphatzements (Ca-P) als Knochenfüller bei oralen Implantaten auszuwerten. Vierundzwanzig stufenförmige Implantate, welche Defekte von 1 und 2 mm kreieren, wurden in den trabekulären Knochen der medialen femoralen Kondylen von 6 Ziegen eingesetzt. Vier verschiedene Situationen wurden getestet: 1) Implantat + Defekte; 2) Implantat + Defekte, aber bedeckt mit einer Membran aus Polimilchsäure; 3) Implantat + Defekte, welche mit Ca-P-Zement gefüllt wurden; 4) Implantat + Defekte, welche mit Ca-P-Zement gefüllt und mit einer Membran bedeckt wurden. Alle implantate wurden 12 Wochen belassen. Histologische und quantitative histomorphometrische Messungen zeigten, dass Implantate + Defekte generell schlechten Knochenkontakt an der Implantatbasis aufwiesen. Ausserdem wurde eine fibröse Einkapselung im Bereich der Defekte beobachtet. Im Gegensatz dazu bewirkte die Präsenz einer Membran das Einwachsen von Knochen in die Defekte und der Knochenkontakt an der Implantatbasis wurde gefördert. Die Injektion von Ca-P-Zement resultierte in einer fast kompletten Auffüllung der Defekte um die Implantate. Die Zementoberfläche war völlig mit Knochen bedeckt. Es konnte eine aktive Resorption und eine Remodellierung der Zementpartikel beobachtet werden. Dies lässt ein Muster mit langsamer Resorption assoziiert mit komplettem Ersatz durch neugebildeten Knochen vermuten. Die zusätzliche Verwendung einer Membran brachte keine weiteren Vorteile. Der Knochen-/Implantat-Kontakt an der Implantatbasis war vergleichbar mit den Implantaten, die nur mit einer Membran abgedeckt worden waren. Zusammenfassend kann festgehalten werden, dass der verwendete Ca-P-Zement eine exzellente Handhabung kombiniert mit ausserodentlichem Knochenverhalten zeigte. Andererseits war die Zersetzungsrate des Materials immer noch sehr Gering. Diese momentanen Eigenschaften können letztendlich die klinische Anwendbarkeit des Materials als Defektfüller bei periimplantären und parodontalen Defekten behindern. Resumen La intención del presente estudio fue evaluar la aplicabilidad clínica y el comportamiento biológico de un cemento recientemente desarrollado de fosfato de calcio (Ca-P) como relleno óseo para huecos alrededor de los implantes orales. Se insertaron veinticuatro implantes del tipo escalón creando huecos de 1 y 2 mm en el hueso trabecular de los cóndilos femorales mediales de 6 cabras. Se probaron cuatro situaciones diferentes: 1) implantes + huecos; 2) implantes + huecos, pero cubiertos con una membrana de ácido poliláctico; 3) implantes + huecos que se rellenaron con cemento de Ca-P; y 4) + huecos que se rellenaron con cemento de Ca-P y se cubrieron con una membrana. Todos los implantes se dejaron en su lugar durante 12 semanas. las mediciones histológicas e histomorfométricas cuantitativas demonstraron que los implantes + huecos tuvieron generalmente un contacto óseo pobre en la base del implante. Posteriormente, se observó una encapsulación fibrosa en la parte del hueco. En contraste, la presencia de la membrana promocionó el crecimiento óseo hacia el hueco y también el contacto óseo en la base del implante. La inyección de cemento Ca-P resultó en un casi completo relleno de los huecos alrededor del implante. La superficie del cemento se cubrió completamente de hueso. La reabsorción activa y la remodelación de las partículas de cemento fueron observadas, lo cual sugiere un patrón de reabsorción lenta asociada con una completa sustitución con hueso neoformado. El uso adicional de la membrana no resultó en beneficios adicionales. El contacto hueso implante en la base del implante fue comparable con los implantes que solo tenían la membrana. En conclusión, el uso de cemento de Ca-P mostró excelentes propiedades de manejo clínico combinado con un superior comportamiento óseo. Por otro lado, el índice de degradación del material fue muy lento. Estas características actuales pueden estorbar la aplicabilidad clínica final del material como rellenador de huecos alrededor de defectos periodontales o perimplantarios. [source]

Mindfulness-Based Interventions in Context: Past, Present, and Future

Jon Kabat-Zinn
Baer's review (2003; this issue) suggests that mindf ulness-based interventions are clinically efficacious, but that better designed studies are now needed to substantiate the field and place it on a firm foundation for future growth. Her review, coupled with other lines of evidence, suggests that interest in incorporating mindfulness into clinical interventions in medicine and psychology is growing. It is thus important that professionals coming to this field understand some of the unique factors associated with the delivery of mindfulness-based interventions and the potential conceptual and practical pitfalls of not recognizing the features of this broadly unfamiliar landscape. This commentary highlights and contextualizes (1) what exactly mindfulness is, (2) where it came from, (3) how it came to be introduced into medicine and health care, (4) issues of cross-cultural sensitivity and understanding in the study of meditative practices stemming from other cultures and in applications of them in novel settings, (5) why it is important for people who are teaching mind-fulness to practice themselves, (6) results from 3 recent studies from the Center for Mindfulness in Medicine, Health Care, and Society not reviewed by Baer but which raise a number of key questions about clinical applicability, study design, and mechanism of action, and (7) current opportunities for professional training and development in mindfulness and its clinical applications. [source]