RepoMed (Medizinische Hochschule Hannover)
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Double semilunar valve replacement in complex congenital heart disease using decellularized homografts
No full textOBJECTIVES: Patients with complex congenital heart disease often require multiple reoperations, resulting in increased rates of operative morbidity and mortality. Decellularized heart valves (DHVs) have led to reduced reoperation rates compared with current other valve substitutes when used for pulmonary valve replacement and have also shown very auspicious early results in aortic valve replacement. The aim of the work was to analyse the outcome of a single-stage decellularized valve implantation in the aortic and pulmonary position. METHODS: A prospective follow-up of all patients who received a single-stage double semilunar valve replacement using DHV at our institution. RESULTS: Since 2011, 5 patients underwent combined semilunar valve replacement with DHV at our institution: two following a Ross procedure (31-year-old man and 38-year-old woman) and 3 after repair of the truncus arteriosus communis (2-year-old boy and 11-year-old and 16-year-old girls). All patients had undergone previous surgery. The Ross patients had preceding valve procedures, and the patients with truncus arteriosus communis had undergone 1 repair and subsequent operative procedures. Despite challenging operations (median bypass time 346 min, range 275-477 min; median cross-clamp time 229 min, range 140-307 min), there was no perioperative mortality or reoperations. Four of the patients were extubated within 24 h, and the other patient was extubated on postoperative day 2. During follow-up, a good semilunar valve and biventricular heart function was present in all 5 patients, and the New York Heart Association functional class was I for all the patients at the time of their latest follow-up (median 31 months, range 8-82 months). The mean echocardiographic gradient of decellularized aortic homografts was 5.4 +/- 3.2 mmHg and 11.6 +/- 4.2 mmHg for the decellularized pulmonary homografts. Valvular regurgitation was 0 or 0-I for all DHVs. CONCLUSIONS: A single-stage double semilunar valve replacement with DHV has shown promising early results in these 5 very complex cases, providing an additional surgical option after multiple preceding valve procedures in young patients
Der entdeckte Resection-Severity-Index ist ein unabhängiger signifikanter prognostischer Faktor für die frühe Mortalität und das Langzeitüberleben nach Leberresektion zur Behandlung des hepatozellulären Karzinoms
Get PDFGot Milk? Breastfeeding and Milk Analysis of a Mother on Chronic Hemodialysis
No full text10.1371/journal.pone.0143340 [doi] AB - PURPOSE: Women on dialysis rarely become pregnant. However, the overall rate of successful pregnancies is increasing in this patient population and breastfeeding becomes an option for mothers on dialysis. In this study we performed a systematic breast milk composition analysis of a mother on chronic hemodialysis (HD). METHODS: Specimens of breast milk and blood were collected in regular intervals before and after HD from a 39-year old woman starting on day 10 postpartum. Samples were analyzed for electrolytes, retention solutes, nutrients and other laboratory measurements. Breast milk samples from low-risk mothers matched for postpartum age were used as controls. RESULTS: Significantly higher levels of creatinine and urea were found in pre-HD breast milk when compared to post-HD. A similar post-dialytic decrease was only found for uric acid but not for any other investigated parameter. Conversely, sodium and chloride were significantly increased in post-HD samples. Compared to controls creatinine and urea were significantly higher in pre-HD samples while the difference remained only significant for post-HD creatinine. Phosphate was significantly lower in pre- and post-HD breast milk when compared to controls, whereas calcium showed no significant differences. In terms of nutrient components glucose levels showed a strong trend for a decrease, whereas protein, triglycerides and cholesterol did not differ. Similarly, no significant differences were found in iron, potassium and magnesium content. CONCLUSION: To the best of our knowledge this is the first report on a breastfeeding mother on chronic dialysis. Although we found differences in creatinine, urea, sodium, chloride and phosphate, our general analysis showed high similarity of our patient's breast milk to samples from low-risk control mothers. Significant variations in breast milk composition between pre- and post-HD samples suggest that breastfeeding might be preferably performed after dialysis treatment. In summary, our findings indicate that breastfeeding can be considered a viable option for newborns of mothers on dialysi
Proteome and Phosphoproteome Analysis in TNF Long Term-Exposed Primary Human Monocytes
No full textTo better understand the inflammation-associated mechanisms modulating and terminating tumor necrosis factor (TNF-)induced signal transduction and the development of TNF tolerance, we analyzed both the proteome and the phosphoproteome in TNF long term-incubated (i.e., 48 h) primary human monocytes using liquid chromatography-mass spectrometry. Our analyses revealed the presence of a defined set of proteins characterized by reproducible changes in expression and phosphorylation patterns in long term TNF-treated samples. In total, 148 proteins and 569 phosphopeptides were significantly regulated (103 proteins increased, 45 proteins decreased; 377 peptides with increased and 192 peptides with decreased phosphorylation). A variety of these proteins are associated with the non-canonical nuclear factor kappaB (NF-kappaB) pathway (nuclear factor kappaB (NFKB) 2, v-rel reticuloendotheliosis viral oncogene homolog (REL) B, indolamin-2,3-dioxygenase (IDO), kynureninase (KYNU)) or involved in the negative regulation of the canonical NF-kappaB system. Within the phosphopeptides, binding motifs for specific kinases were identified. Glycogen synthase kinase (GSK) 3 proved to be a promising candidate, since it targets NF-kappaB inhibiting factors, such as CCAAT/enhancer binding protein (C/EBP) beta. Our experiments demonstrate that both proteome and phosphoproteome analysis can be effectively applied to study protein/phosphorylation patterns of primary monocytes. These results provide new regulatory candidates and evidence for a complex network of specific but synergistically acting/cooperating mechanisms enabling the affected cells to resist sustained TNF exposure and resulting in the resolution of inflammatio
Validation of the German Version of the Power of Food Scale in a General Population Sample
No full textOBJECTIVE: The Power of Food Scale (PFS) is a self-report instrument for assessing appetitive motivation in the absence of caloric needs. The study aim was to validate the German PFS version in a large population sample. METHODS: Complete information on all PFS items was available from 2,421 respondents (age >/=14) of a nationally representative sample of the German population. We examined the psychometric properties of the German PFS version and provided population-based normative data. RESULTS: The 3-factor structure of the original scale was replicated in confirmatory factor analysis. The German PFS version demonstrated good internal consistency (alpha = 0.92 for the total scale). It was well accepted by the respondents, as indicated by a low proportion of missing item values
Between Innate and Adaptive Immune Responses: NKG2A, NKG2C, and CD8+ T Cell Recognition of HLA-E Restricted Self-Peptides Acquired in the Absence of HLA-Ia
Get PDFOn healthy cells the non-classical HLA class Ib molecule HLA-E displays the cognate ligand for the NK cell receptor NKG2A/CD94 when bound to HLA class I signal peptide sequences. In a pathogenic situation when HLA class I is absent, HLA-E is bound to a diverse set of peptides and enables the stimulatory NKG2C/CD94 receptor to bind. The activation of CD8(+) T cells by certain p:HLA-E complexes illustrates the dual role of this low polymorphic HLA molecule in innate and adaptive immunity. Recent studies revealed a shift in the HLA-E peptide repertoire in cells with defects in the peptide loading complex machinery. We recently showed that HLA-E presents a highly diverse set of peptides in the absence of HLA class Ia and revealed a non-protective feature against NK cell cytotoxicity mediated by these peptides. In the present study we have evaluated the molecular basis for the impaired NK cell inhibition by these peptides and determined the cell surface stability of individual p:HLA-E complexes and their binding efficiency to soluble NKG2A/CD94 or NKG2C/CD94 receptors. Additionally, we analyzed the recognition of these p:HLA-E epitopes by CD8(+) T cells. We show that non-canonical peptides provide stable cell surface expression of HLA-E, and these p:HLA-E complexes still bind to NKG2/CD94 receptors in a peptide-restricted fashion. Furthermore, individual p:HLA-E complexes elicit activation of CD8(+) T cells with an effector memory phenotype. These novel HLA-E epitopes provide new implications for therapies targeting cells with abnormal HLA class I expression
Inhibition of Heme Oxygenase-1 Activity Enhances Wilms Tumor-1-Specific T-Cell Responses in Cancer Immunotherapy
Get PDFWilms tumor protein-1 (WT1) is an attractive target for adoptive T-cell therapy due to its expression in solid tumors and hematologic malignancies. However, T cells recognizing WT1 occur in low frequencies in the peripheral blood of healthy donors, limiting potential therapeutic possibilities. Tin mesoporphyrin (SnMP) is known to inhibit heme oxygenase-1 (HO-1), which has been shown to boost the activation and proliferation of human virus-specific T cells. We analyzed the influence of this effect on the generation of WT1-specific T cells and developed strategies for generating quantities of these cells from healthy donors, sufficient for adoptive T-cell therapies. HO-1 inhibition with SnMP increased WT1-specific T-cell frequencies in 13 (26%) of 50 healthy donors. To assess clinical applicability, we measured the enrichment efficiency of SnMP-treated WT1-specific T cells in response to a WT1-specific peptide pool and a HLA-A*02:01-restricted WT1 peptide by cytokine secretion assay. SnMP treatment resulted in a 28-fold higher enrichment efficacy with equal functionality. In conclusion, pharmacological inhibition of HO-1 activity with SnMP results in more efficient generation of functionally active WT1-specific T cells. This study demonstrates the therapeutic potentials of inhibiting HO-1 with SnMP to enhance antigen-specific T-cell responses in the treatment of cancer patients with WT1-positive disease
