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Skin transformed into liver cells to treat an inherited disease

MedWorm Lung Transplant - Wed, 10/12/2011 - 16:23
The procedure, designed to treat an inherited liver condition, could herald a new era of therapies for genetic disordersScientists have taken skin cells from a patient with liver disease and turned them into replacement liver cells, in a biological tour de force that promises to transform how the condition is treated.The procedure will have to undergo several years of trials before it can be used in humans, but if approved, it could launch a new era of personalised therapies for serious genetic disorders.In Britain 30,000 people carry a genetic defect that causes antitrypsin deficiency, a disease that can only be cured by a liver transplant. The operation requires a suitable donor organ and costs around £500,000, with drugs to prevent rejection by the immune system adding more than £20,0...
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Diagnosis and Management of Diffuse Lung Disease in Children

MedWorm Lung Transplant - Wed, 10/12/2011 - 03:00
Summary: Diffuse lung disease [DLD] in children comprises a group of heterogeneous, rare disorders. Despite the rarity of these diseases there has been a considerable increase in our knowledge of DLD in children including their diagnosis and management. Diagnosis of these diseases requires a detailed history and physical examination, diagnostic imaging, pulmonary function testing, selected and directed laboratory testing, bronchoalveolar lavage and in most cases an open lung biopsy. Once a diagnosis is made, treatment is centred on supportive care including nutritional and supplemental oxygen therapy when needed. Medications including corticosteroids and other immunomodulatory medications are often used. Lung transplantation has been used for final treatment in some cases of DLD. Formation...
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Human peripheral blood CD4 T cell‐engrafted non‐obese diabetic‐scid IL2rγnull H2‐Ab1 tm1Gru Tg (human leucocyte antigen D‐related 4) mice: a mouse model of human allogeneic graft‐versus‐host disease

MedWorm Lung Transplant - Tue, 10/11/2011 - 21:52
SummaryGraft‐versus‐host disease (GVHD) is a life‐threatening complication of human allogeneic haematopoietic stem cell transplantation. Non‐obese diabetic (NOD)‐scid IL2rγnull (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)‐GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno‐GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG‐H2‐Ab1 tm1Gru, NSG‐Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II ...
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Disseminated mucormycosis infection after the first course of dose-modified R-EPOCH for advanced-stage lymphoma

MedWorm Lung Transplant - Tue, 10/11/2011 - 14:49
We report the case of a 63-year-old man who presented at our hospital after experiencing fever and dyspnea for more than 1 month. Because his general condition was deteriorating, he was referred to our intensive care unit. He needed critical care and was treated with vasopressors, artificial ventilation, and continuous hemodialysis. Considering his systemic condition, hematological malignancy was suspected. Bone marrow and skin biopsies were performed, and the condition was diagnosed as diffuse large B-cell lymphoma. On the 15th day, suspecting infectious lung disease, we performed bronchoscopy, which showed Rhizopus infection. Thus, the patient was administered high-dose liposomal amphotericin B (10 mg/kg) therapy. On the 54th day, he died of a massive pulmonary hemorrhage....
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New Journal Seeks Submissions: Transplantation Research

MedWorm Lung Transplant - Mon, 10/10/2011 - 14:30
Transplantation Research,  the latest initiative from open access publisher BioMed Central, is now accepting submissions. The journal provides a forum for the rapid release of cutting-edge experimental and clinical research in transplantation, as well as discussion of ethical issues relating to organ donation. Among the research topics included in Transplantation Research are:   organ preservation  ischemia-reperfusion injury and inflammation  histocompatibility  pharmacological/experimental immunosuppression  immune recognition – regulation, and tolerance induction strategies  stem cell research for tissue regeneration/repair and immune regulation  early-stage clinical trials and clinical trial protocols  innovative method protocols  complications of transplantation, incl...

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Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure

MedWorm Lung Transplant - Mon, 10/10/2011 - 03:00
Background: Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity.Methods: Eighty-three stable patients with mild–moderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m2) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO2, %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thena...
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Salt induces biosynthesis of hemolytically active compounds in the xerotolerant food‐borne fungus Wallemia sebi

MedWorm Lung Transplant - Fri, 10/07/2011 - 22:50
AbstractWallemia sebi is a xerotolerant, ubiquitous, food‐borne, mycotoxigenic fungus. An ethanol extract of its mycelium demonstrated a strong hemolytic activity, which was further enhanced at high salt concentrations in the growth medium. Characterization of the extract using gas chromatography–mass spectrometry revealed a mixture of sterols and unsaturated fatty acids, indicating the latter as responsible for the hemolytic activity. The lytic activity of the extract is here studied using red blood cells and artificial small lipid vesicles with various lipid compositions. This shows concentration‐dependent hemolysis, and preferential activity towards lipid membranes with greater fluidity. The W. sebi lytic activity on mammalian erythrocytes shows its potential involvement in the f...
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Computer-Aided Diagnosis and Artificial Intelligence in Clinical Imaging

MedWorm Lung Transplant - Thu, 10/06/2011 - 19:05
Computer-aided diagnosis (CAD) is rapidly entering the radiology mainstream. It has already become a part of the routine clinical work for the detection of breast cancer with mammograms. The computer output is used as a “second opinion” in assisting radiologists' image interpretations. The computer algorithm generally consists of several steps that may include image processing, image feature analysis, and data classification via the use of tools such as artificial neural networks (ANN). In this article, we will explore these and other current processes that have come to be referred to as “artificial intelligence.” One element of CAD, temporal subtraction, has been applied for enhancing interval changes and for suppressing unchanged structures (eg, normal structures) between 2 succe...
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Multidisciplinary Management of Recurrent Hepatocellular Carcinoma Following Liver Transplantation

MedWorm Lung Transplant - Thu, 10/06/2011 - 05:28
Conclusion  Late recurrence of HCC following transplantation should be borne in mind even after many years from transplant. Surgical salvage, when feasible, remains a viable treatment option in select patients with a chance for long-term survival. A multi-disciplinary approach is critical as different therapeutic modalities have a role in treating recurrent HCC following transplant. Content Type Journal ArticleCategory Review ArticlePages 1-8DOI 10.1007/s11605-011-1710-8Authors Peter J. Kneuertz, Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USADavid P. Cosgrove, Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of M...
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Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation

MedWorm Lung Transplant - Thu, 10/06/2011 - 03:00
As familial amyloid polyneuropathy (FAP) is an adult-onset disease, a long period is expected between domino liver transplantation (DLT) and the occurrence of amyloidosis in recipients of a FAP liver. However, as time passes, and increased numbers of patients have undergone DLT, patients with symptoms suggesting amyloidosis have been reported. The authors describe, for the first time, pathological findings in an autopsy case of a recipient of a FAP liver. A male patient with primary sclerosing cholangitis received a liver graft from a FAP patient with the transthyretin (TTR) Tyr114Cys mutation when he was 30 years old. Although a recurrence of primary sclerosing cholangitis was detected at age 34, he had no symptoms indicating amyloidosis. He died from Burkitt's lymphoma at 38 ye...

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Case studies of the spatial heterogeneity of DNA viruses in the cystic fibrosis lung.

MedWorm Lung Transplant - Thu, 10/06/2011 - 03:00
Authors: Willner D, Haynes MR, Furlan M, Hanson N, Kirby B, Lim YW, Rainey PB, Schmieder R, Youle M, Conrad D, Rohwer F Abstract Microbial communities in the lungs of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients have been shown to be spatially heterogeneous. Viral communities may also vary spatially, leading to localized viral populations and infections. Here, we characterized viral communities from multiple areas of the lungs of two late-stage CF patients using metagenomics: the explanted lungs from transplant patient and lungs acquired post-mortem. All regions harbored eukaryotic viruses which may infect the human host, notably herpesviruses, anelloviruses, and papillomaviruses. In the highly diseased apical lobes of the explant lungs, viral dive...
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Acute Hyperglycemic Exacerbation of Lung Ischemia-Reperfusion Injury is Mediated by RAGE Signaling.

MedWorm Lung Transplant - Thu, 10/06/2011 - 03:00
The objective of this study was twofold: 1) evaluate the impact of acute hyperglycemia on lung IR injury, and 2) determine if RAGE signaling is a mechanism of hyperglycemia-enhanced IR injury. We hypothesized that acute hyperglycemia worsens lung IR injury through a RAGE signaling mechanism. C57BL/6 wild-type (WT) and RAGE knockout (RAGE-/-) mice underwent sham thoracotomy or lung IR (1hr left hilar occlusion and 2hrs reperfusion). Acute hyperglycemia was established by dextrose injection 30 min prior to ischemia. Lung injury was assessed by measuring lung function, cytokine expression in bronchoalveolar lavage fluid, leukocyte infiltration, and microvascular permeability via Evans blue dye. Mean blood glucose levels doubled in hyperglycemic mice 30 min after dextrose injection. Compared t...
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Clinical and radiological features of respiratory syncytial virus in solid organ transplant recipients: a single‐center experience

MedWorm Lung Transplant - Thu, 10/06/2011 - 03:00
ConclusionSOT recipients accounted for half of all adult cases of RSV at our institution. Type and length of treatment varied widely, and we cannot conclude that outcomes differed between treatments with oral or inhaled ribavirin. Current therapeutic management of RSV in SOT is empiric, and can be rather expensive and difficult, without clear evidence of effectiveness. (Source: Transplant Infectious Disease)
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Exercise Does a Renal-Impaired Body Good

MedWorm Kidney Transplant - Wed, 10/05/2011 - 22:43
Regular exercise improves health for chronic kidney disease patients, a Cochrane review affirmed.
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Cell Therapy Lowers Drug Needs After Kidney Transplant

MedWorm Kidney Transplant - Wed, 10/05/2011 - 21:00
Inducing immune tolerance with donor CD34+ hematopoietic progenitor cells and T cells may lessen the need for lifelong immunosuppressive drugs after kidney transplant, researchers said.
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Bayesian Probit Regression Model for the Diagnosis of Pulmonary Fibrosis: Proof-of-Principle.

MedWorm Lung Transplant - Wed, 10/05/2011 - 03:00
Conclusions: This study represents the first use of BPR on whole lung tissue; previously, BPR was primarily used to develop predictive models for cancer. This also represents the first report of an independently validated IPF gene expression signature. In summary, BPR is a promising tool for the development of gene expression signatures from non-neoplastic lung tissue. In the future, BPR might be used to develop definitive diagnostic gene signatures for IPF, prognostic gene signatures for IPF or gene signatures for other non-neoplastic lung disorders such as bronchiolitis obliterans. (Source: BMC Medical Genomics)
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Who Needs an RVAD in Addition to an LVAD?

MedWorm Heart Transplant - Mon, 10/03/2011 - 03:00
Mechanical circulatory support using left ventricular assist devices (LVAD) has become an accepted mode of therapy for both bridging patients with end-stage heart failure to transplant and as a destination therapy. Right ventricular (RV) dysfunction is common after LVAD insertion and is a significant source of morbidity and mortality in patients undergoing LVAD placement. Several studies have identified clinical, laboratory, hemodynamic, and echocardiographic parameters that may serve as risk factors for RV dysfunction after LVAD placement. Furthermore, scoring systems have been established to help quantitatively predict the potential need for RV support after LVAD placement. (Source: Cardiology Clinics)
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Toward Total Implantability Using Free-Range Resonant Electrical Energy Delivery System: Achieving Untethered Ventricular Assist Device Operation Over Large Distances

MedWorm Heart Transplant - Mon, 10/03/2011 - 03:00
Heart failure is a terminal disease with a very poor prognosis. Although the gold standard of treatment remains heart transplant, only a minority of patients can benefit from transplants. Another promising alternative is mechanical circulatory assistance using ventricular assist devices. The authors envision a completely implantable cardiac assist system affording tether-free mobility in an unrestricted space powered wirelessly by the innovative Free-Range Resonant Electrical Energy Device (FREE-D) system. Patients will have no power drivelines traversing the skin, and this system will allow power to be delivered over room distances and will eliminate trouble-prone wirings, bulky consoles, and replaceable batteries. (Source: Cardiology Clinics)
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Long-term follow-up of cardiac resynchronization therapy: mechanical resynchronization and reverse left ventricular remodeling are predictive for long-term transplant-free survival

MedWorm Heart Transplant - Sat, 10/01/2011 - 05:43
Abstract  We sought to determine whether correction of mechanical left ventricular (LV) dyssynchrony as defined by tissue Doppler imaging (TDI) is predictive for transplant-free long-term survival in patients (pts.) undergoing cardiac resynchronization therapy (CRT). In 76 CRT recipients TDI curves from the septal, lateral, anterior, and inferior basal LV were obtained at baseline and after 6 Â± 4 months. A time difference between regional electromechanical delays (EMD) of ≥40 ms was considered dyssynchronous. At follow-up, pts. were classified as TDI-responders (TDI-R: dyssynchrony at baseline, corrected by CRT) versus non-responders (TDI-NR: either not dyssynchronous at baseline, or persisting dyssynchrony). Pts. were then followed by standard echocar...
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Combining tricuspid valve repair with double lung transplantation in patients with severe pulmonary hypertension, tricuspid regurgitation, and right ventricular dysfunction.

MedWorm Lung Transplant - Sat, 10/01/2011 - 03:00
CONCLUSIONS: Combined TVR and DLTx procedures were successfully performed without an increase in morbidity or mortality and contributed to decreased primary graft dysfunction. In our experience, this combined operative approach achieves clinical outcomes equal or superior to the outcomes seen in DLTx patients without RV dysfunction and severe tricuspid regurgitation. PMID: 21700686 [PubMed - in process] (Source: Chest)

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