A Qualitative and Quantitative Analysis of Protein Substitution in Human Burn Wounds

Objective: In major burn wounds of more than 15% total burn surface area mediator-associated reactions lead to capillary leak resulting in critical condition. Little is known about the efficiency of protein substitution. We quantified and qualified the systemic and local protein loss in burn patients during protein substitution, comparing fresh frozen plasma and the human serum protein solution Biseko. Methods: In 40 patients suffering from second-degree burn wounds with the total burn surface area between 20% and 60%, immediately after admission a defined wound surface area was enclosed with in a wound chamber. Wound fluid and serum samples were collected in 8 hour intervals for 2 days. Samples were analyzed for total protein, albumin, immunoglobulins -A, -G, -M, clotting parameters, c-reactive protein, and white blood cells. Protein substitution started 24 hour posttrauma. In a randomized pattern, patients received equal volumes of fresh frozen plasma or Biseko. Results: Total protein and albumin accumulated in high concentrations in wound fluid. With beginning of fresh frozen plasma substitution on day 2 posttrauma, serum total protein (1.7 g–3.9 g) and albumin (1.3 g–3.4 g) concentrations increased. Substitution of Biseko resulted in a stronger increase (serum total protein 1.8 g to 4.5 g, albumin 0.9 g to 3.4 g). Wound fluid concentrations revealed similar change patterns. Immunoglobulins showed higher serum levels in the Biseko group. C-reactive protein and white blood cell values indicated a lower immunological reaction in the Biseko group. Conclusions: Substitution of human protein solutions such as Biseko can result in significantly higher serum protein and albumin concentrations as well as lower infection parameters. Higher serum immunoglobulins could help to decrease potential immunodeficiency

Feasibility of chemosensitivity testing in soft tissue sarcomas

BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet

Burn wounds infected with Pseudomonas aeruginosa triggers weight loss in rats

BACKGROUND: Despite dramatic improvements in the management of burns, infection still remains a serious risk for the burn patient. The aim of this study was to shed light on the impact of acute burn injury with or without infection on cytokine profiles. METHODS: Sprague-Dawley rats (n = 21) were randomized into three groups: 1) burn only 2) burn and infection or 3) sham burn. Weight was monitored and blood was collected for cytokine ELISA, LPS quantification, and peripheral blood analysis. Animals were sacrificed either after 6 or 12 days. RESULTS: Infected animals showed substantial weight loss until day 6 post-burn as compared to burn alone. Endotoxin and TNF-α levels were elevated early in the infected burn group within 48 hours post-burn. In contrast, significant up-regulation of the anti-inflammatory cytokine IL-10 occurred later in the clinical course and was associated with the recovery from weight loss. CONCLUSION: Our results suggest that in the presence of infection, you get a SIRS response possibly due to transient endotoxemia that is only seen in the infection group. In contrast, both burn and infection get a late IL-10 (CARS) response, which is then associated with a return to normal weight in the infection group