ABSTRACT
PURPOSE: Transforming growth factor beta (TGF-beta) bioactivity has been implicated as a potential regulator of the transition from scarless healing to scar formation in fetal wounds. Decorin is an extracellular matrix proteoglycan that regulates TGF-beta bioactivity and assists in collagen fibrillogenesis. To determine its role in scarless repair, the authors examined decorin expression in fetal fibroblasts, skin, and wounds. METHODS: A single, full-thickness, 2-mm open wound was created on the dorsal surface of fetal rats at 16.5 days (E16) and 18.5 days (E18) gestational age (term, 21.5 days [E21]). Wounds were harvested at 24 and 72 hours (n = 12 wounds per time-point). Nonwounded fetal skin at E17, E19, and E21 was harvested for analysis of decorin expression during skin development and as controls for wounds. In addition, fetal (E14, E18) and adult dermal fibroblasts were cultured for in vitro analysis. Reduced-cycle, specific primer, reverse transcriptase polymerase chain reaction was performed to quantitate decorin expression. RESULTS: Decorin expression increased rapidly with increasing gestational age in both fetal fibroblasts and skin. Expression was increased 22-fold in E18 fibroblasts (P <.002) and 300-fold in adult fibroblasts (P <.001) compared with E14 fibroblasts. In skin, expression increased 74% (P <.01) during the fetal wound healing transition period between E17 and E19. However, in E16 wounds (scarless), decorin expression decreased 59% (P <.006) at 24 hours and 45% (P <.02) at 72 hours. Decorin expression did not change in E18 (scar) wounds at 24 and 72 hours (P >.05). CONCLUSIONS: Early gestation fetal fibroblasts and fetal skin express decorin at lower levels than late gestation fetal and adult fibroblasts and skin. Decorin expression is down-regulated in scarless (E16) compared with scar (E18) wounds. Thus, increased decorin expression is associated with both skin development and scar formation. Conversely, decreased decorin expression is associated with scarless repair.
Subject(s)
Cicatrix/metabolism , Fetus/metabolism , Fibroblasts/metabolism , Proteoglycans/metabolism , Skin/metabolism , Wound Healing/physiology , Animals , Cicatrix/etiology , Cicatrix/pathology , Decorin , Extracellular Matrix Proteins , Female , Phenotype , Pregnancy , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Skin/cytology , Transforming Growth Factor beta/metabolismABSTRACT
PURPOSE: Renal failure occurs in children with moderate frequency. Surgical aspects of establishing and maintaining dialysis access in small infants are exceptionally challenging. The purpose of this review is to evaluate the authors' experience with dialysis access for infants less than 10 kg, particularly with respect to the surgical care required. METHODS: A retrospective review was conducted between 1991 and 1999 of all pediatric dialysis patients weighing 10 kg or less (n = 29). Age at start of dialysis, duration of dialysis, modes of dialysis, and complications specific to peritoneal (PD) and hemodialysis (HD) were examined. RESULTS: The mean age at start of dialysis was 10.4 months and continued for an average duration of 16.3 months. Seventy-two percent of all patients required both modes of dialysis. HD and PD duration averaged 7.8 and 10.5 months, respectively. Catheter durability was 3.1 and 4.5 months per catheter for HD and PD, respectively. There was no significant difference in complications when comparing HD and PD. Patients who weighed 5 to 10 kg had significantly longer PD catheter durability than patients 0 to 5 kg (P = .001). Forty-one percent of patients terminated dialysis after transplantation, whereas 24% died awaiting transplantation. CONCLUSION: Despite a large number of operations required, infants less than 10 kg can be bridged successfully, by surgical intervention and subsequent dialysis, to transplantation.
Subject(s)
Catheters, Indwelling , Peritoneal Dialysis/methods , Renal Dialysis/methods , Renal Insufficiency/therapy , Body Weight , Female , Humans , Infant , Infant, Newborn , Male , Peritoneal Dialysis/mortality , Probability , Renal Insufficiency/diagnosis , Renal Insufficiency/mortality , Renal Insufficiency/surgery , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Surgical Procedures, Operative/methods , Survival Rate , Treatment OutcomeABSTRACT
Transforming growth factor-beta (TGF-beta1, -beta2, and -beta3) has been implicated in the ontogenetic transition from scarless fetal repair to adult repair with scar. Generally, TGF-beta exerts its effects through type I and II receptors; however, TGF-beta modulators such as latent TGF-beta binding protein-1 (LTBP-1), decorin, biglycan, and fibromodulin can bind and potentially inhibit TGF-beta activity. To more fully explore the role of TGF-beta ligands, receptors, and potential modulators during skin development and wound healing, we have used a rat model that transitions from scarless fetal-type repair to adult-type repair with scar between days 16 and 18 of gestation. We showed that TGF-beta ligand and receptor mRNA levels did not increase during the transition to adult-type repair in fetal skin, whereas LTBP-1 and fibromodulin expression decreased. In addition, TGF-beta1 and -beta3; type I, II, and III receptors; as well as LTBP-1, decorin, and biglycan were up-regulated during adult wound healing. In marked contrast, fibromodulin expression was initially down-regulated in adult repair. Immunostaining demonstrated significant fibromodulin induction 36 hours after injury in gestation day 16, but not day 19, fetal wounds. This inverse relationship between fibromodulin expression and scarring in both fetal and adult rat wound repair suggests that fibromodulin may be a biologically relevant modulator of TGF-beta activity during scar formation.
