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

Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on tissue necrosis in SKH1-hr hairless mice

<p>Abstract</p> <p>Objective</p> <p>Tissue hypoxia after blood loss, replantation and flap reperfusion remains a challenging task in surgery. Normovolemic hemodilution improves hemorheologic properties without increasing oxygen carrying capacity. Red blood cell transfusion is the current standard of treatment with its attendant risks. The aim of this study was to investigate the potential of the chemically modified hemoglobin, MP4, to reduce skin flap necrosis and its effect on selected blood markers and kidneys.</p> <p>Materials and methods</p> <p>Tissue ischemia was induced in the ear of hairless mice (n = 26). Hemodilution was performed by replacing one third of blood volume with the similar amount of MP4, dextran, or blood. The extent of non-perfused tissue was assessed by intravital fluorescent microscopy.</p> <p>Results</p> <p>Of all groups, MP4 showed the smallest area of no perfusion (in percentage of the ear ± SEM: 16.3% ± 2.4), the control group the largest (22.4% ± 3.5). Leukocytes showed a significant increase in the MP4 and dextran group (from 8.7 to 13.6 respectively 15.4*10⁹/l). On histology no changes of the kidneys could be observed.</p> <p>Conclusion</p> <p>MP4 causes an increase of leukocytes, improves the oxygen supply of the tissue and shows no evidence of renal impairment.</p

Proximal major limb amputations – a retrospective analysis of 45 oncological cases

<p>Abstract</p> <p>Background</p> <p>Proximal major limb amputations due to malignant tumors have become rare but are still a valuable treatment option in palliation and in some cases can even cure. The aim of this retrospective study was to analyse outcome in those patients, including the postoperative course, survival, pain, quality of life, and prosthesis usage.</p> <p>Methods</p> <p>Data of 45 consecutive patients was acquired from patient's charts and contact to patients, and general practitioners. Patients with interscapulothoracic amputation (n = 14), shoulder disarticulation (n = 13), hemipelvectomy (n = 3) or hip disarticulation (n = 15) were included.</p> <p>Results</p> <p>The rate of proximal major limb amputations in patients treated for sarcoma was 2.3% (37 out of 1597). Survival for all patients was 42.9% after one year and 12.7% after five years. Survival was significantly better in patients with complete tumor resections. Postoperative chemotherapy and radiation did not prolong survival. Eighteen percent of the patients with malignant disease developed local recurrence. In 44%, postoperative complications were observed. Different modalities of postoperative pain management and the site of the amputation had no significant influence on long-term pain assessment and quality of life. Eighty-seven percent suffered from phantom pain, 15.6% considered their quality of life worse than before the operation. Thirty-two percent of the patients who received a prosthesis used it regularly.</p> <p>Conclusion</p> <p>Proximal major limb amputations severely interfere with patients' body function and are the last, albeit valuable, option within the treatment concept of extremity malignancies or severe infections. Besides short survival, high complication rates, and postoperative pain, patients' quality of life can be improved for the time they have remaining.</p

Physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues : a scoping review

Deep tissue injuries are pressure ulcers which initiate in the subcutaneous tissues and extend through a bottom-up pathway. Once deep tissue injuries are visual at skin level, serious irreversible tissue damage has already occurred. In pressure ulcer development, inflammation and edema are coupled physiological processes associated with tissue damage arising due to sustained mechanical loading. This study aimed to provide an in-depth overview of the physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues, in the context of pressure ulceration. A scoping review was performed according to the framework by Arksey and O'Malley. The databases MEDLINE, EMBASE, Web of Science, and Scopus, and the reference lists of included studies were searched for in vivo (animal, human), and in vitro studies matching the study objectives (from inception to 28 May 2018). No restrictions for inclusion were applied for study design, setting, participants, and year of publication. A total of 12 studies were included, varying in study design, sample characteristics, amount and duration of mechanical loads that were applied, follow-up time, and assessment methods. Neutrophil infiltration and edema occur in the subcutaneous tissues nearly immediately after the application of load on soft tissues. The amount of neutrophils and edema increase in the first days after the mechanical insult and decrease once healing has been initiated and no supplementary mechanical load was applied. One study indicated that edema may extend up to the level of the dermo-epidermal junction. Further research should focus on how deep tissue inflammation and edema are reflected into unique tissue changes at skin level, and how abnormal inflammatory responses manifest (e.g. when the nervous system is not functioning normally)

Suppression of Soft Tissue Sarcoma Growth by a Host Defense-Like Lytic Peptide

BACKGROUND: Soft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum. METHODS: In vitro the human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide and recordings using scanning electron microscopy could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immunocompetent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed. RESULTS: The peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative, antiangiogenic activity of the treatment group. CONCLUSION: These findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models

Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial

Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m−2) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m−2) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4–6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m−2 plus CI-5FU 225 mg m−2 was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39–82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m−2 plus CI-5FU 225 mg m−2 with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC