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Bone response to submerged implants in organ transplant patients: a prospective controlled study.

Fri, 07/19/2013 - 22:03
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Bone response to submerged implants in organ transplant patients: a prospective controlled study.

Int J Oral Maxillofac Implants. 2012 Nov-Dec;27(6):1494-500

Authors: Montebugnoli L, Venturi M, Cervellati F

Abstract
PURPOSE: To compare the short-term outcome of dental implant therapy in a group of organ transplant patients with that of a control group.
MATERIALS AND METHODS: The study population included consecutive organ transplant patients and consecutive normal (healthy) subjects as controls. Two films were taken of all patients: one at baseline (implant placement) and one after 3 months of healing. All radiographs were analyzed twice (15 days apart) blindly by two independent trained radiologists. Crestal bone level (CBL) was measured, defined as the perpendicular distance from the reference point on the implant to the first visible apical bone-to-implant contact.
RESULTS: The study population included 10 organ transplant patients (eight hearts, two livers) and 10 control patients, who received 20 and 12 submerged dental implants, respectively. At the 3-month follow-up visit, no implants showed any exposed cover screws. CBL increased in both groups, without any significant difference between the groups (CBL increased from 0.08±0.09 mm to 0.28±0.20 mm in transplant patients and from 0.11±0.16 mm to 0.42±0.32 mm in controls). Multiple analysis of variance showed that the mean bone loss of 0.21±0.18 mm observed in the group of transplant patients was not statistically different from that (0.32±0.25 mm) seen in the control group and was not influenced by any of the variables considered.
CONCLUSIONS: The present pilot study seems to indicate that the bone response around submerged dental implants in immunocompromised organ transplant patients does not differ from that observed in control patients and that this particular population of patients may be successfully rehabilitated with dental implants.

PMID: 23189301 [PubMed - indexed for MEDLINE]

Controlled angiogenesis in the heart by cell-based expression of specific vascular endothelial growth factor levels.

Fri, 07/19/2013 - 22:03
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Controlled angiogenesis in the heart by cell-based expression of specific vascular endothelial growth factor levels.

Hum Gene Ther Methods. 2012 Oct;23(5):346-56

Authors: Melly LF, Marsano A, Frobert A, Boccardo S, Helmrich U, Heberer M, Eckstein FS, Carrel TP, Giraud MN, Tevaearai HT, Banfi A

Abstract
Vascular endothelial growth factor (VEGF) can induce normal angiogenesis or the growth of angioma-like vascular tumors depending on the amount secreted by each producing cell because it remains localized in the microenvironment. In order to control the distribution of VEGF expression levels in vivo, we recently developed a high-throughput fluorescence-activated cell sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a specific VEGF dose from a heterogeneous primary population. Here we tested the hypothesis that cell-based delivery of a controlled VEGF level could induce normal angiogenesis in the heart, while preventing the development of angiomas. Freshly isolated human adipose tissue-derived stem cells (ASC) were transduced with retroviral vectors expressing either rat VEGF linked to a FACS-quantifiable cell-surface marker (a truncated form of CD8) or CD8 alone as control (CTR). VEGF-expressing cells were FACS-purified to generate populations producing either a specific VEGF level (SPEC) or uncontrolled heterogeneous levels (ALL). Fifteen nude rats underwent intramyocardial injection of 10(7) cells. Histology was performed after 4 weeks. Both the SPEC and ALL cells produced a similar total amount of VEGF, and both cell types induced a 50%-60% increase in both total and perfused vessel density compared to CTR cells, despite very limited stable engraftment. However, homogeneous VEGF expression by SPEC cells induced only normal and stable angiogenesis. Conversely, heterogeneous expression of a similar total amount by the ALL cells caused the growth of numerous angioma-like structures. These results suggest that controlled VEGF delivery by FACS-purified ASC may be a promising strategy to achieve safe therapeutic angiogenesis in the heart.

PMID: 23075102 [PubMed - indexed for MEDLINE]

A 22-year old female with cardiogenic shock due to transplant vasculopathy with severe left main stenosis.

Fri, 07/19/2013 - 22:03
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A 22-year old female with cardiogenic shock due to transplant vasculopathy with severe left main stenosis.

Int J Cardiol. 2012 Dec 15;162(1):e14-5

Authors: Wenzel P, Genth-Zotz S, Kasper-König W, Vahl CF, Münzel T, Gori T

PMID: 22622055 [PubMed - indexed for MEDLINE]

Endobronchial hamartoma.

Wed, 07/17/2013 - 12:45

Endobronchial hamartoma.

J Bronchology Interv Pulmonol. 2013 Jul;20(3):247-8

Authors: Poonja Z, Sobey A, Weinkauf JG

Abstract
We present images of an endobronchial hamartoma visible by bronchoscopy in the left lower lobe. A 56-year-old woman with a late presentation of an acute anterior myocardial infarction requires urgent heart transplantation and subsequently has trouble weaning off the ventilator. Bronchoscopic evaluation reveals a 1cm endobronchial hamartoma obstruction the left lower lobe bronchus. A polypectomy snare was effectively used with electrocautery to excise the lesion. The patient was successfully able to wean off the ventilator once the left lower lobe was free from obstruction.

PMID: 23857199 [PubMed - in process]

Vascular endothelial growth factor in heart failure.

Wed, 07/17/2013 - 12:45

Vascular endothelial growth factor in heart failure.

Nat Rev Cardiol. 2013 Jul 16;

Authors: Taimeh Z, Loughran J, Birks EJ, Bolli R

Abstract
Heart failure is a devastating condition, the progression of which culminates in a mismatch of oxygen supply and demand, with limited options for treatment. Heart failure has several underlying causes including, but not limited to, ischaemic heart disease, valvular dysfunction, and hypertensive heart disease. Dysfunctional blood vessel formation is a major problem in advanced heart failure, regardless of the aetiology. Vascular endothelial growth factor (VEGF) is the cornerstone cytokine involved in the formation of new vessels. A multitude of investigations, at both the preclinical and clinical levels, have garnered valuable information on the potential utility of targeting VEGF as a treatment option for heart failure. However, clinical trials of VEGF gene therapy in patients with coronary artery disease or peripheral artery disease have not, to date, demonstrated clinical benefit. In this Review, we outline the biological characterization of VEGF, and examine the evidence for its potential therapeutic application, including the novel concept of VEGF as adjuvant therapy to stem cell transplantation, in patients with heart failure.

PMID: 23856679 [PubMed - as supplied by publisher]

"Flexo-dyspnea": A novel clinical observation in the heart failure syndrome.

Wed, 07/17/2013 - 12:45

"Flexo-dyspnea": A novel clinical observation in the heart failure syndrome.

J Heart Lung Transplant. 2013 Aug;32(8):844-5

Authors: Brandon N, Mehra MR

PMID: 23856222 [PubMed - in process]

Left ventricular retraining after arterial switch operation facilitated by mechanical circulatory support.

Wed, 07/17/2013 - 12:45

Left ventricular retraining after arterial switch operation facilitated by mechanical circulatory support.

J Heart Lung Transplant. 2013 Aug;32(8):842-3

Authors: Di Chiara L, Ricci Z, Brancaccio G, Gandolfo F, Amodeo A

PMID: 23856221 [PubMed - in process]

Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia.

Wed, 07/17/2013 - 12:45

Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia.

J Heart Lung Transplant. 2013 Aug;32(8):832-8

Authors: Gohrbandt B, Avsar M, Warnecke G, Sommer SP, Haverich A, Strueber M

Abstract
BACKGROUND: Topical in situ cooling of the donor lungs is a prerequisite for procurement of non-heart-beating donor lungs and may be of interest for living related lung donation.
METHODS: Twenty-four single lung transplants were performed in 4 groups of Landrace pigs (6 per group). Control LPD, control Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel) ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of solution at 4°C. Lungs were stored immersed in preservation solution for 24 hours at 4°C. After transplantation of the left lung, the right recipient bronchus and pulmonary artery were clamped.
RESULTS: Four of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7-hour reperfusion. The mean oxygenation index was favorably preserved in the exCel group at 7 hours after reperfusion (417 ± 81) over all other groups (LPD 341 ± 133, Celsior 387 ± 86, exLPD 327 ± 76; p < 0.0001). Pulmonary vascular resistance showed significantly lower values in the Celsior and exCel groups (LPD 1,310 ± 620, Celsior 584 ± 194, exLPD 1,035 ± 361, exCel 650 ± 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001). Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft protection in the exCel group (LPD 8.1 ± 0.8, Celsior 8.4 ± 0.8, exLPD 7.5 ± 1.0, exCel 3.1 ± 0.9; p < 0.0001).
CONCLUSION: Initial topical cooling followed by backtable perfusion is a sufficient technique for pulmonary graft preservation providing excellent post-transplant function. Celsior subsequent to in-situ topical cooling revealed the most beneficial results in this setting. This combined technique could advance non-heart-beating, living related lung lobe donation and, potentially, regular heart-beating lung donation.

PMID: 23856220 [PubMed - in process]

Partial mechanical circulatory support in an ovine model of post-infarction remodeling.

Wed, 07/17/2013 - 12:45

Partial mechanical circulatory support in an ovine model of post-infarction remodeling.

J Heart Lung Transplant. 2013 Aug;32(8):815-22

Authors: Geens JH, Jacobs S, Claus P, Trenson S, Leunens V, Vantichelen I, Rega FR, Verbeken EK, Burkhoff D, Meyns B

Abstract
BACKGROUND: Full unloading of the left ventricle (LV) in chronic heart failure (CHF) induces reversal of LV dilation and geometric distortion. In this study we describe the partial unloading effects in ischemic CHF.
METHODS: Six weeks after myocardial infarction, sheep were randomized to partial support ("pump," n = 5), as provided by the CircuLite Synergy micro-pump, or to no therapy ("sham," n = 6) for an additional 6 weeks. At baseline, and at 6 and 12 weeks after infarction, pressure-volume (PV) recordings were made. Systolic and diastolic functions were characterized by the end-systolic volume (ESV) where LV end-systolic pressure reached 90 mm Hg (V90), and the end-diastolic volume (EDV) where LV end-diastolic pressure reached 15 mm Hg (V15), respectively. Magnetic resonance imaging (MRI) was performed 6 and 12 weeks after infarction. During autopsy at 12 weeks, isolated LVs were weighed. Histologically, the degree of fibrosis in the non-infarcted area was assessed using systematic randomized sampling, and myocyte hypertrophy was measured by the mean linear intercept method.
RESULTS: At 6 weeks, PV measurements showed a V90 and V15 increase (p = NS between groups). Six weeks later, V90 and V15 increased in the sham group. In the pump group, V90 decreased but V15 did not change significantly. At 6 weeks, MRI indicated no significant difference between groups. Six weeks later, in the sham group, EDV and ESV increased significantly. In the pump group, EDV decreased significantly and ESV trended to decrease. Sphericity index increased in the sham group and decreased in the pump group, although not significantly. Explanted LV masses were significantly higher in the sham group than in the pump group. The pump group had a decrease in fibrosis and less myocyte hypertrophy.
CONCLUSION: Partial support 6 weeks after major myocardial infarction halts and reverses ventricular dilation and hypertrophy.

PMID: 23856219 [PubMed - in process]

Pre-transplant antibodies to Kα1 tubulin and collagen-V in lung transplantation: Clinical correlations.

Wed, 07/17/2013 - 12:45

Pre-transplant antibodies to Kα1 tubulin and collagen-V in lung transplantation: Clinical correlations.

J Heart Lung Transplant. 2013 Aug;32(8):807-14

Authors: Tiriveedhi V, Gautam B, Sarma NJ, Askar M, Budev M, Aloush A, Hachem R, Trulock E, Myers B, Patterson AG, Mohanakumar T

Abstract
BACKGROUND: Immune responses to lung-associated self-antigens (SAgs) have been implicated in chronic lung allograft rejection. The goals of this study were to determine the prevalence of pre-existing antibodies (Abs) to the SAgs in pulmonary diseases and the association between pre-existing Abs to SAgs and the development of primary graft dysfunction (PGD), donor-specific antibodies (DSA), and chronic rejection.
METHODS: Pre- and post-transplant sera were analyzed from 317 lung transplant (LTx) recipients between 2000 and 2011 with diagnosis of chronic obstructive disease (n = 161), idiopathic pulmonary fibrosis (IPF; n = 50), cystic fibrosis (CF; n = 55), and others (n = 51). Samples were analyzed for Abs to SAgs by enzyme-linked immunosorbent assay, and DSA and cytokines by Luminex. The clinical diagnosis of PGD and bronchiolitis obliterans syndrome (BOS) was based on International Society for Heart and Lung Transplantation guidelines.
RESULTS: The overall prevalence of Abs to SAgs was 22.71%, including 18% in chronic obstructive pulmonary disease (p = 0.033), 34% in IPF (p = 0.0006), 29% in CF (p = 0.0023), and 19.6% in other diagnoses (p = 0.044). The incidence of PGD (88% vs 54%, p < 0.05), DSA (70% vs 45%, p < 0.01), and BOS (90% vs 38% (p < 0.001) after LTx was significantly higher in patients with pre-LTx Abs to SAgs than without. Pro-inflammatory cytokines (interleukin-1β, interleukin-17, and interferon-γ) were elevated in patients who had pre-LTx Abs to SAgs, along with a reduction in anti-inflammatory interleukin-10.
CONCLUSIONS: Patients with IPF and CF have the highest prevalence of Abs to SAgs. Patients with pre-existing Abs to SAgs are at increased risk for development of PGD, DSA, and BOS. Strategies to remove pre-existing Abs to SAgs should be considered to improve lung allograft outcome.

PMID: 23856218 [PubMed - in process]

Changes in body composition after lung transplantation in children.

Wed, 07/17/2013 - 12:45

Changes in body composition after lung transplantation in children.

J Heart Lung Transplant. 2013 Aug;32(8):800-6

Authors: Kyle UG, Spoede ET, Mallory GB, Orellana R, Shekerdemian LS, Schecter MG, Coss-Bu JA

Abstract
BACKGROUND: The evaluation of nutritional status, including body composition measurements, in pediatric patients before and after lung transplant (LTx) can aid in adapting nutrition support and physical rehabilitation programs to meet individual patient needs. The purpose of this retrospective study was to determine the changes in weight, lean body mass (LBM), and body fat (BF) before and after LTx and their association with lung function in pediatric patients.
METHODS: Included were 41 LTx patients, aged 3 months to 20.7 years, who had at least 2 body composition measurements determined by dual-energy X-ray absorptiometry (GE Lunar Prodigy, Waukesha, WI) in the first 2 years after LTx were measured pre-LTX and at 12 or 24 months post-LTX, for weight, LBM, and BF.
RESULTS: Pre-LTx, 29% of patients had moderate and 12% had severe chronic malnutrition (growth stunting). This compares with 21% of patients being moderately LBM-depleted and 23% being BF-depleted. The weight change at 12 and 24 months was +9.3% (interquartile range, 5.6%-23%) and +4.7% (0.9%-11.6%), respectively; whereas the LBM change at 12 and 24 months was +15.2% (6.8%-17.1%) and +4.2% (-0.6% to 7.7%), respectively. LBM percentiles correlated with pulmonary function tests ( % predicted forced vital capacity [ρ = 0.36, p = 0.001] and forced expiratory volume in 1 second [ρ = 0.265, p = 0.015).
CONCLUSIONS: Maximum weight and LBM gain occur at 12 months after LTx, with smaller gains noted at 24 months. Clinicians must look beyond height and weight and evaluate LBM and fat mass in pediatric patients after LTx.

PMID: 23856217 [PubMed - in process]

Increased right-to-left ventricle diameter ratio is a strong predictor of right ventricular failure after left ventricular assist device.

Wed, 07/17/2013 - 12:45

Increased right-to-left ventricle diameter ratio is a strong predictor of right ventricular failure after left ventricular assist device.

J Heart Lung Transplant. 2013 Aug;32(8):792-9

Authors: Vivo RP, Cordero-Reyes AM, Qamar U, Garikipati S, Trevino AR, Aldeiri M, Loebe M, Bruckner BA, Torre-Amione G, Bhimaraj A, Trachtenberg BH, Estep JD

Abstract
BACKGROUND: Predictors of right ventricular failure (RVF) in patients with left ventricular assist devices (LVADs) have not been fully elucidated and are comprised mostly of clinical variables. We evaluated echocardiographic parameters associated with adverse outcomes in this population.
METHODS: Transthoracic echocardiograms (TTEs) before continuous-flow LVAD implantation were analyzed in 109 patients. Twenty-six 2-dimensional and Doppler parameters were assessed for their association with the primary outcome of 30-day RVF, defined as a requirement of an RV assist device or ≥14 consecutive days of inotropic support, and the secondary composite outcome of 30-day death or RVF. Multivariate analysis adjusted for known clinical risk prediction models was performed.
RESULTS: Overall, 25 (22.9%) and 27 (24.8%) patients reached the primary and secondary end-points, respectively. An increased RV/LV diameter ratio was the only TTE variable independently associated with both the primary (odds ratio [OR] = 5.40; 95% confidence interval [CI] 2.40 to 12.40; p = 0.012) and secondary (OR = 2.70; 95% CI 1.06 to 6.22; p = 0.03) outcomes after multivariate analysis. Scatterplot analysis with regression determined the optimal cut-off value for RV/LV diameter to be 0.75. Based on receiver operating characteristic curves, an increased RV/LV diameter ratio provided an additional predictive value to clinical risk scores.
CONCLUSIONS: A TTE-measured RV/LV diameter ratio of ≥0.75 is independently associated with a higher risk for RVF in patients with continuous-flow LVAD. When used alone, this simple, easily derived, practical echocardiographic measurement has a predictive value equivalent to known clinical risk scores, whereas their combination provides stronger risk prediction for adverse outcomes.

PMID: 23856216 [PubMed - in process]

Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation.

Wed, 07/17/2013 - 12:45

Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation.

J Heart Lung Transplant. 2013 Aug;32(8):784-91

Authors: Matsuo Y, Cassar A, Yoshino S, Flammer AJ, Li J, Gulati R, Topilsky Y, Raichlin E, Lennon RJ, Lerman LO, Rihal CS, Kushwaha SS, Lerman A

Abstract
BACKGROUND: The aim of the study was to assess temporal changes in plaque size and components after heart transplantation (HTx), and to evaluate the differences in treatment effects on plaque progression between sirolimus and calcineurin inhibitors (CNIs).
METHODS: The study comprised 146 HTx recipients who were converted from CNIs to sirolimus as primary immunosuppressant (sirolimus group, n = 61) and those who were maintained on CNIs (CNI group, n = 85). A retrospective compositional analysis of serial virtual histology-intravascular ultrasound was performed.
RESULTS: During a median follow-up of 2.8 years, there was a significant difference in plaque volume in favor of sirolimus between groups (p = 0.004). When subjects were sub-classified according to the time interval between HTx and study inclusion, those in the early group (≤2 years after HTx) had a greater increase in plaque volume (p = 0.006), characterized by a higher progression rate of fibrous plaque volume (p = 0.01). The treatment difference between groups in plaque volume was identified in the early group in favor of sirolimus with attenuating effects on the progression of fibrous plaque component (both p = 0.03 for interaction). By contrast, there were significant differences in necrotic core and dense calcium volume (both p < 0.05 for interaction) in favor of CNIs in the late group (≥6 years after HTx).
CONCLUSIONS: Compared with continued CNI therapy, sirolimus attenuated plaque progression in recipients with early conversion, but contributed to increases in necrotic core and dense calcium volume in those with late conversion. Our study supports the hypothesis that early initiation of sirolimus offers greater benefits in the treatment of CAV.

PMID: 23856215 [PubMed - in process]

Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation.

Wed, 07/17/2013 - 12:45

Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation.

J Heart Lung Transplant. 2013 Aug;32(8):769-76

Authors: Tible M, Loupy A, Vernerey D, Suberbielle C, Beuscart T, Cazes A, Guillemain R, Amrein C, Pezzella V, Fabiani JN, Nochy D, Hill G, Empana JP, Jouven X, Charron D, Bruneval P, Duong Van Huyen JP

Abstract
BACKGROUND: Humoral immune responses during heart transplantation may result in antibody-mediated rejection (AMR), which is now taken into account on endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR (pAMR) grades of the International Society for Heart and Lung Transplantation classification. This classification might benefit from new immunohistological markers and validation by others biomarkers, namely donor-specific antibodies (DSA).
METHODS: From the 293 protocol EMBs performed in 113 patients in our institution during a 1-year period for this prospective study, 280 EMB specimens were available with both histology and immunohistochemistry. C4d and labeling of intravascular cells by cluster of differentiation (CD) 68 were performed on paraffin sections. Available sera (n = 150) concomitant of EMB specimens were tested for the presence of DSA. All of the pAMR+ EMB specimens, along with a set of randomized pAMR0 EMB specimens, were immunolabeled for mammalian target of rapamycin (mTOR) effectors, phosphorylated 70 S6-kinase (p70S6K) and phosphorylated S6 ribosomal protein (pS6RP).
RESULTS: AMR was diagnosed in 37 EMB specimens (13.2%): 1 pAMR1(I+), 27 pAMR1(H+), and 9 pAMR2. The proportion of DSA-positive EMB varied according to the pAMR grade, with pAMR0, pAMR1(H+), and pAMR2 EMB presenting 17.6%, 77.3%, and 100% of DSA-positivity, respectively. Among the 30 pAMR+ specimens with available DSA testing and the 30 pAMR0 randomized specimens, mTOR pathway immunohistochemistry showed endothelial cell positivity for p70S6K in 17 pAMR+ EMB specimens (56.7%) and in 1 pAMR0 EMB specimen (3.3%). pS6RP was detected in 8 pAMR+ EMB specimens (26.7%) and in 1 pAMR0 EMB specimen (3.3%).
CONCLUSIONS: p70S6K and pS6RP immunohistochemistry afford new markers of AMR on EMB specimens because their expression is correlated with microcirculation inflammation and DSA. The correlation of DSA with pAMR grade suggests that this grading system is valid.

PMID: 23856214 [PubMed - in process]

Impact of nutritional state on lung transplant outcomes: The weight of the evidence.

Wed, 07/17/2013 - 12:45

Impact of nutritional state on lung transplant outcomes: The weight of the evidence.

J Heart Lung Transplant. 2013 Aug;32(8):755-6

Authors: Shah P, Orens JB

Abstract
Despite advances in perioperative and post-operative management, lung transplant recipients with select pre transplant risk factors have been shown to experience worse post-transplant outcomes in comparison to those without such risk factors. Among these variables, previous studies have shown that select markers of poor nutritional status prior to transplant, such as low body mass index (BMI) and hypoalbuminemia, have been associated with increased post-transplant mortality. In a past issue of the journal, Chamogeorgakis el al. examine a comprehensive battery markers previously associated with malnutrition to determine their impact on outcomes after lung transplantation. The authors find that hypoalbuminemia is associated with worse survival, but does not appear to affect the risk of post-transplant infections. This article reviews the study presented by Chamogeorgakis et al. to discuss how it furthers our understanding of the impact of nutritional status on transplant-related outcomes and consider areas for future investigation.

PMID: 23856213 [PubMed - in process]

Comparison of CEDIA FK506 assay with HPLC/MS/MS in a large cohort of pediatric patients.

Wed, 07/17/2013 - 12:45
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Comparison of CEDIA FK506 assay with HPLC/MS/MS in a large cohort of pediatric patients.

Am J Clin Pathol. 2013 Jun;139(6):788-92

Authors: Lower DR, Cropcho L, Rosendorff A

Abstract
FK506 (tacrolimus), a macrolide immunosuppressant, is widely used in pediatric transplant patients, but a relatively narrow therapeutic window in children vs adults requires close and accurate monitoring of whole blood FK506 levels. High-pressure liquid chromatography/tandem mass spectrometry (HPLC/MS/MS)-based assays have been viewed as the gold standard but are more time and labor intensive than cloned enzyme donor immunoassay (CEDIA). To analyze differences between the 2 assays, we assayed FK506 in 348 split samples simultaneously by both methods. A further 70 samples were stratified by organ transplantation type: cardiac (13%), renal (23%), small bowel (22%), or liver transplantation (42%). Results were analyzed using standard statistical techniques for method comparison. CEDIA overestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 40% of cases (139/348), whereas CEDIA underestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 13.5% of cases, for a total inaccuracy of 53% using a ±20% cutoff. Only 28% of samples (99/348) measured by CEDIA were within 10% of the value obtained by HPLC/MS/MS. Bland-Altman analysis showed a mean bias of 9.5% in favor of CEDIA over HPLC/MS/MS (95% confidence interval, 6.1%-12.9%). Positive bias was greatest for liver transplant and R(2) values were lowest for intestinal transplant patients, indicating that HPLC/MS/MS may be a better option for this pediatric transplant subgroup.

PMID: 23690122 [PubMed - indexed for MEDLINE]

Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy.

Tue, 07/16/2013 - 12:45

Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy.

Stem Cells Int. 2013;2013:353097

Authors: Miteva K, Van Linthout S, Volk HD, Tschöpe C

Abstract
Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined.

PMID: 23853610 [PubMed - as supplied by publisher]

Interactions of the heart and the liver.

Tue, 07/16/2013 - 12:45

Interactions of the heart and the liver.

Eur Heart J. 2013 Jul 12;

Authors: Møller S, Bernardi M

Abstract
There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic cardiomyopathy. Electrophysiological abnormalities include prolonged QT interval, chronotropic incompetance, and electromechanical uncoupling. No specific therapy can be recommended, but it should be supportive and directed against the heart failure. Numerous conditions affect both the heart and the liver such as infections, inflammatory and systemic diseases, and chronic alcoholism. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since the perioperative mortality is high, a careful cardiac evaluation of such patients is required prior to orthotopic liver transplantation.

PMID: 23853073 [PubMed - as supplied by publisher]

Effects of Ivabradine on 6-Minute Walk Test and Quality of Life in Patients With Previously Implanted CRT-D.

Tue, 07/16/2013 - 12:45

Effects of Ivabradine on 6-Minute Walk Test and Quality of Life in Patients With Previously Implanted CRT-D.

J Investig Med. 2013 Jul 11;

Authors: Ates I, Yavuz AH, Doğru M, Genç A, Ulucan S, Sarkaya M, Cetinkaya R, Keser A, Akpek M, Kaya MG

Abstract
BACKGROUND: We aimed to evaluate clinical effects of additional heart rate control by ivabradine on life quality score and 6-minute walking test in patients with previously implanted biventricular cardiac resynchronization therapy defibrillator (CRT-D) with ischemic heart failure under regular treatment.
METHODS: Fifteen men and 14 women with a median age of 63 years (range, 48-79 years) were studied. Twenty-one patients were in New York Heart Association class II (8 patients were in class III), CRT-D implanted previously, and with resting heart rates greater than 70 beats per minute with sinus rhythm despite conventional medication. Patients were given 2.5- to 7.5-mg ivabradine orally twice a day, and drug dosage was titrated to decrease the patients' average heart rate to 70 beats per minute. Before and 3 months after ivabradine treatment, all patients underwent extensive clinical, echocardiographic, and laboratory evaluation.
RESULTS: Ivabradine treatment produced dose-dependent reductions in heart rate at rest and at peak exercise (91.9 ± 6.3 to 71.7 ± 4.8 and 114.4 ± 7.6 to 96.8 ± 4.8; P = 0.001 and P = 0.001, respectively). There were also significant improvements in life quality score (52.4 ± 9.5 to 37.9±7.8; P = 0.001) and 6-minute walking distance (278.7 ± 85.8 to 373.3 ± 94.0; P = 0.001) of patients. All patients with New York Heart Association class III became class II after 3 months of ivabradine treatment.
CONCLUSION: Heart rate reduction in a short-term period by ivabradine produced significant improvements in exercise capacity and life quality in patients with CRT-D and conventional therapy.

PMID: 23851959 [PubMed - as supplied by publisher]

Hair Follicle Transplantation on Scar Tissue.

Tue, 07/16/2013 - 12:45

Hair Follicle Transplantation on Scar Tissue.

J Craniofac Surg. 2013 Jul;24(4):1239-1241

Authors: Jung S, Oh SJ, Hoon Koh S

Abstract
BACKGROUND: Hair transplantation is a continuously evolving field. The procedure was originally developed by Dr. Orentreich in 1959, but he applied it only to the androgenic alopecia. Potential applications for hair grafting extend beyond treatment of hair loss.
METHODS: Our study group consisted of 25 cases of 23 patients. The causes of scar resulting to hair loss were burns, operation, and trauma. The scalp strips or follicular unit extracts were harvested from occipital, posterior auricular, dog-eared scalp, adjacent scalp area, and nuchal area. The recipient sites were scalp, eyebrow, lip, and eyelid.
RESULTS: The follow-up cases over 6 months after operation were 18 among total 25 cases. The result after hair follicle transplantation was excellent (44.4%), good (38.9%), fair (11.1%), and poor (5.6%).
CONCLUSIONS: The hair follicle transplantation on the scar tissue is more difficult than grafting on normal tissue because the scar is accompanied by poor blood circulation and stiffness of tissue. The patients with burned scar achieved more favorable result than did others. Incision scars are deeper than burned scars, and their success rates are poor. We should recommend the patients that hair follicle transplantation on the scar may need secondary or more operations for the aesthetically better result.

PMID: 23851778 [PubMed - as supplied by publisher]

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