Differential glycosaminoglycan expression and hyaluronan homeostasis in juvenile hyaline fibromatosis.

BACKGROUND: Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease characterized histologically by deposition of hyaline material and clinically by multiple skin lesions. Clarification of the molecular and structural changes involved in JHF skin lesions may unravel targets for pharmacotherapy. OBJECTIVE: We sought to investigate the expression of glycosaminoglycans and their metabolizing enzymes in lesional as compared with lesion-free skin tissue specimens in JHF. METHODS: Glycosaminoglycans were isolated, purified, and fractionated by electrophoresis on cellulose acetate membranes and agarose gels. Hyaluronic acid (HA) was quantitated by enzyme-linked immunosorbent assay and the expression of HA metabolizing enzymes was investigated using reverse transcriptase-polypeptide chain reaction. RESULTS: JHF lesions exhibited significantly less HA and elevated amounts of dermatan sulfate and chondroitin sulfate, whereas gene expression of HA synthase-1 and HA synthase-3 was significantly down-regulated, as compared with lesion-free skin tissue specimens. LIMITATIONS: Because JHF is a rare disease, a limitation to our study was that we collected skin tissue specimens from only one patient. CONCLUSION: The significant alterations of HA homeostasis in JHF lesions provide further understanding of JHF pathogenesis and may offer a target for pharmacologic intervention to treat the skin lesions associated with JHF.

The efficacy of antithrombin administration in the acute phase of burn injury.

Severe burn injury is characterized by the activation of coagulation, decreased fibrinolytic activity and decreased natural anticoagulant activity. The aim of our study was to investigate the effect of antithrombin (AT) administration on coagulation status and on organ function in the early post-burn period. Thirty-one patients were admitted to the burn intensive care unit and were then randomised into two groups (AT-treated and non-AT-treated) for four consecutive days after thermal injury. The clinical data, coagulation and fibrinolysis parameters were compared and the adverse effects were monitored. Significant differences in the time course of coagulation markers (thrombin/AT complexes, tissue plasminogen activator, D-dimer) were observed between AT-treated and non-AT treated groups. According to the International Society on Thrombosis and Haemostasis criteria, disseminated intravascular coagulation (DIC) diagnosis was made in 28 of 31 patients. The presence of overt DIC was associated with mortality (p < 0.001). The Sequential Organ Failure Assessment (SOFA) score time trend differed significantly between the two investigation groups (decreased in the treated group and did not change in the non-AT-treated group). AT-treated patients had an absolute reduction in a 28-day mortality of 25% as compared to the non-AT-treated group (p = 0.004). No treatment related side effects were observed. Treatment with AT seems to affect the coagulation status and reduce multiple organ failure incidence and mortality in the early post-burn period.

Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis?

OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN AND SETTING: Prospective, observational study in a four bed Burn Intensive Care Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.