PR05POST‐OPERATIVE HAEMATOMAS IN MICROVASCULAR FREE FLAP RECONSTRUCTION OF THE HEAD AND NECK: THE INCIDENCE,AETIOLOGY AND OUTCOME MODIFICATIONS

Background Free tissue transfer using microvascular surgery has become a safe a reliable means to repair soft tissue and/or bony defects of the head and neck. Operative success reaches 98%, however the incidence of significant post‐operative complication is also relatively high (32%). One common and often severe complication is haematoma formation at either donor or recipient sites. The incidence of recipient site haematoma is reported at 6%, however the causes and outcomes of haematomas have not been well investigated. A retrospective historical analysis of both donor and recipient site wound haematoma was performed to identify causative factors and the effect on patient outcome. Methodology A five year review was conducted for microvascular free tissue transfer to defects in the head and neck at The Royal Melbourne Hospital, for the period from February 2001 until February 2006. The medical records of these 150 patients were reviewed for donor and recipient site wound haematoma and outcomes. Results Significant factors for the development of post‐operative haematomas included lood pressure control during the first post‐operative, correlating with the likelihood of developing either a donor or recipient site haematoma (p value < 0.001), drain‐tube outputs (both high and low), smoking and the use of pre‐operative NSAIDs. Conclusion There are significant reversible factors that contribute to the development of post‐operative haematomas in head and neck surgery. Close monitoring of patient blood pressure by theatre and recovery nursing staff, close monitoring of drain outputs, and pre‐operative counselling on the use of NSAIDs and smoking may all be useful in the prevention of haematoma formation.     

Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients

Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD.     

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells

Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34+ peripheral blood stem cells (CD34+ PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34+ PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34+ cells. CXCR4-transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs.     

Recently amplified satellite DNA inCallithrix argentata (Primates,Platyrrhini)

A satellite DNA has been cloned from the neotropical primateCallithrix argentata and designated CarB. The presence of the satellite was assayed in New and Old World primates by blot hybridization: CarB is highly amplified in the genomes of all three species belonging to theC. argentata species group (C. argentata, C. emiliae, C. humeralifer), but is either absent, or present in only minor amounts, in other primates, including the closely related species,C. jacchus. A completely sequenced CarB monomeric unit was 1528 bp in length and mapped to the telomeric C-band-positive regions of manyC. argentata species group chromosomes. Sequence data from eight CarB clones indicated an average difference of 3.5% when base substitutions alone were counted. The hybridization and sequence data suggest that this satellite underwent a period of amplification and dispersal in the genome of a recent ancestor of theC. argentata species group.     

Trans-Epithelial Transport,Metabolism, and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met)

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.