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In this canine carotid model, FG with FGF-1 and heparin did not induce significant intimal or medial thickening after 10 or 30 days when compared with vessels that were only balloon-injured. The seeding of autologous ECs within the FG/FGF-1/heparin suspension caused a reduction in neointima formation with no concomitant medial thickening 30 days after injury. The use of FG to locally deliver FGF-1 and ECs may have clinical relevance in the inhibition of intimal hyperplasia.

Epidermolysis bullosa (EB) with late-onset muscular dystrophy (EB-MD) is a hemidesmosomal variant of EB due to mutations in the plectin gene (PLEC1). The age of onset of muscle involvement has been noted to vary from infancy to the fourth decade of life. Immunofluorescence of the patients' skin and muscle biopsies is usually negative for staining with antibodies recognizing plectin, a large cytoskeleton-associated anchorage protein. In this study we report novel plectin mutations in two families with EB. In both families, the proband was a newborn with neonatal blistering with no evidence for muscle weakness as yet. Peripheral blood DNA was isolated and examined by heteroduplex scanning strategy, protein truncation test (PTT), and/or direct sequencing of the plectin gene. One of the probands was compound heterozygote for nonsense mutations E2005X/K4460X, and the proband in the second family was compound heterozygote for deletion mutations 5083delG/2745-9del21, the latter mutation extending from -9 to +12 at the intron 22/exon 23 border. The mutations K4460X and 5083delG were not present in either one of the parents, thus being de novo events. In both cases, nonpaternity was excluded by microsatellite marker analysis. The stop codon mutations are predicted to result in the synthesis of a truncated protein lacking the carboxy-terminal globular domain of the protein and possibly causing nonsense-mediated decay of the corresponding mRNA. The 2745-9del21 deletion mutation abolishes the splice site at the intron 22/exon 23 junction, predicting abnormal splicing events. Because plectin deficiency is associated with muscular dystrophy, molecular diagnostics of the plectin gene provides prognostic value in evaluation of these patients who appear to be at risk to develop muscular dystrophy.

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C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.

Compliance matching between the host vessel and vascular grafts used for small-diameter arterial replacements is thought to be important for long-term patency. However, currently available grafts elicit fibroplastic reactions, resulting in decreasing compliance with time after implantation. Bioresorbable prostheses elicit ingrowth of myofibroblasts containing abundant contractile elements. This led us to investigate whether compliance of implanted bioresorbable prostheses decreased as a function of time and if the kinetics of change correlated with the progression of tissue ingrowth. Woven polyglactin 910 prostheses (10 mm x 4 mm i.d.) were implanted into adult NZW rabbit infrarenal aortas and replicates were harvested serially through 8 months. Control grafts were implanted, and immediately resected. Dynamic compliance was measured at 1-mm axial increments along each explant using a pulse duplicator apparatus which exposed the harvested samples to realistic pulsatile hemodynamics. Compliance was calculated for proximal, mid, and distal segments of each graft and averaged at each time point by grouping into control (zero time, n = 3), early (1-4 weeks, n = 13), and late (6-36 weeks, n = 9) explant periods. At late explant periods both proximal and distal compliance were significantly greater than mid graft compliance (p < .02 and p < .03, respectively). There was a significant increase in proximal compliance between early and late explant times (p < .01). Measured increases in mid and distal segment compliance over time did not reach statistical significance. Myofibroblast laden tissue ingrowth into the inner capsule followed macrophage phagocytosis and was nearly complete prior to the time that an increase in compliance was demonstrated. Thus since the major histologic episodes precede the change in compliance, these are not likely initiated by this biomechanical change. We hypothesize the graft resorption coupled with the ingrowth of more compliant tissue likely leads to the increased compliance of the graft material.