NPWT has been used on many different types of traumatic and non traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas in the wound and improved wound healing.

Objective. Hedgehog signaling not only plays crucial roles during human development but also has been implicated in the pathogenesis of several diseases in adults. The aim of the present study was to investigate the role of the hedgehog pathway in fibroblast activation in systemic sclerosis (SSc).Methods. Activation of the hedgehog pathway was analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). The effects of sonic hedgehog (SHH) on collagen synthesis were analyzed by reporter assays, real-time PCR, and Sircol assays. Myofibroblast differentiation was assessed by quantification of ␣-smooth muscle actin and stress fiber staining. The role of hedgehog signaling in vivo was analyzed by adenoviral overexpression of SHH and using mice lacking 1 allele of the gene for inhibitory receptor Patched homolog 1 (Ptch ؉/؊ mice).Results. SHH was overexpressed and resulted in activation of hedgehog signaling in patients with SSc, with accumulation of the transcription factors Gli-1 and Gli-2 and increased transcription of hedgehog target genes. Activation of hedgehog signaling induced an activated phenotype in cultured fibroblasts, with differentiation of resting fibroblasts into myofibroblasts and increased release of collagen. Adenoviral overexpression of SHH in the skin of mice was sufficient to induce skin fibrosis. Moreover, Ptch ؉/؊ mice with increased hedgehog signaling were more sensitive to bleomycin-induced dermal fibrosis.Conclusion. We demonstrated that the hedgehog pathway is activated in patients with SSc. Hedgehog signaling potently stimulates the release of collagen and myofibroblast differentiation in vitro and is sufficient to induce fibrosis in vivo. These findings identify the hedgehog cascade as a profibrotic pathway in SSc.

This study investigated the effect of thrombospondin-1 (TSP-1) on the formation of cartilage repair tissue in combination with stimulation by osteogenic protein-1 (OP-1). In miniature pigs, articular cartilage lesions in the femoral trochlea were treated by the microfracture technique and either received no further treatment (MFX), or were treated by additional application of recombinant osteogenic protein-1 (MFX+OP-1), recombinant TSP-1 (MFX+TSP-1), or a combination of both proteins (MFX+TSP-1+OP-1). Six and 26 weeks after surgery, the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods detecting collagen types I, II, X, TSP-1, and CD31. Microfracture treatment merely induced the formation of inferior fibrocartilaginous repair tissue. OP-1 stimulated chondrogenesis, but also induced chondrocyte hypertrophy, characterized by synthesis of collagen type X, and excessive bone formation. Application of TSP-1 inhibited inadvertant endochondral ossification, but failed to induce chondrogenesis. In contrast, the simultaneous application of both TSP-1 and OP-1 induced and maintained a permanent, nonhypertrophic chondrocyte-like phenotype within cartilage repair tissue. The data of this study demonstrate that OP-1 and TSP-1 complement each other in a functional manner. While OP-1 induces chondrogenesis of the ingrowing cells, TSP-1 prevents their further hypertrophic differentiation and prevents excessive endochondral ossification within the lesions.

Moxifloxacin is a fluoroquinolone with a broad spectrum of activity and good penetration into many tissues, including bone. Penetration of moxifloxacin into bone has not yet been studied using compartmental modeling techniques. Therefore, we determined the rate and extent of bone penetration by moxifloxacin and evaluated its pharmacodynamic profile in bone via Monte Carlo simulation. Twenty-four patients (10 males, 14 females) undergoing total hip replacement received 400 mg moxifloxacin orally 2 to 7 h prior to surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen by a cryogenic mill, including an internal standard. Drug concentrations were analyzed by high-performance liquid chromatography. We used ADAPT II (results reported), NONMEM, and WinBUGS for pharmacokinetic analysis. Quinolones are established in the treatment of osteomyelitis. Most clinical experience has been gained with ciprofloxacin and ofloxacin (28). Oral administration of quinolones was efficacious in surgical prophylaxis, even after a single dose (6, 39), and also facilitates prolonged therapy. In in vitro studies, Staphylococcus aureus penetrates and survives in bone cells, i.e., osteoblasts (25); therefore, quinolones, which penetrate intracellularly, might be of advantage.Moxifloxacin achieves high concentrations in many tissues. Good penetration into bone has been reported for several quinolones. The average bone/serum concentration ratio in humans at approximately 2 to 5 h postdosing was 0.33 to 0.54 for moxifloxacin (30,34,35).Resistance to the older quinolones has been emerging, and they do not show sufficient microbiological efficacy against S. aureus and coagulase-negative staphylococci and streptococci (28). Moxifloxacin has improved activity against gram-positive and anaerobic pathogens frequently encountered as causative agents in osteomyelitis (28), such as staphylococci, enterobacteriaceae, streptococci, and Haemophilus influenzae (19).Moxifloxacin has lower MICs than do levofloxacin, ciprofloxacin, ofloxacin, and norfloxacin for S. aureus (51), which is the most common pathogen of osteomyelitis. The main causative bacteria for osteomyelitis are S. aureus (methicillin susceptible or resistant), coagulase-negative staphylococci, propionibacteria, streptococci, and Pseudomonas aeruginosa (27). P. aeruginosa can cause osteomyelitis due to nosocomial infections or chronic unresolved middle ear infections in children.Studying the time course and extent of bone penetration before investigating the agent in a clinical trial is important (17,51). Bone penetration studies most often report the ratio of concentrations in bone and serum. However, the ratio of tissue concentrations to serum concentrations of a drug changes with time, a phenomenon known as system hysteresis, and therefore, the concentration ratio depends on the sampling time. Like in the present study, bone penetration of antimicrobials is most often studied in patients undergoing joint replacement, where only one bone sample can...

Objective. Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc.Methods. Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age-and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan-endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests.Results. The numbers of podoplanin-and prox-1-positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score.Conclusion. These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc.