Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas.

BACKGROUND: Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. METHODS: To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. RESULTS: The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. CONCLUSIONS: Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.

Severe burn injuries induced by PUVA chemotherapy.

Psoralen-ultraviolet A (PUVA) chemotherapy is an established treatment for certain skin diseases. Burn injury is a serious complication of PUVA therapy. Reports regarding this complication are limited. The aim of this study was to determine the management and outcome of severe PUVA burns. A retrospective review of the medical records of PUVA burns treated at our burn center from 2000 to 2010 was conducted. Data collected included age, sex, condition, mode of PUVA, site, surface area involved, depth of burns, onset of reactions, treatment, and inpatient stay. To evaluate the incidence of this severe complication, a survey of all listed burn care units in Germany, Austria, and Switzerland as well as the legal advisory boards of the medical associations of the federal states of Germany was conducted. The conditions leading to photochemotherapy were three cases of psoriasis vulgaris and one case of severe chronic graft vs host disease. All patients received oral psoralen. Incorrect handling of the radiation system was the reason for all burns. The mean affected TBSA was 73±18%. All patients were treated conservatively and healed without surgical intervention. Burn injury is a serious and preventable complication of PUVA photochemotherapy. Patients should be advised regarding the potential risk of major burns. Care should be given to not exceed the safe dose of psoralen. Burn care specialists must restrain surgical intervention as even deep partial thickness PUVA burns have the potential to heal spontaneously.

The effectiveness of pedicled groin flaps in the treatment of hand defects: results of 49 patients.

PURPOSE: Despite the growing number of free and local flaps used for repairing defects of the hand, groin flaps are also still widely used. The aims of this study were to evaluate the outcome of a large series of patients whose defects were covered by pedicled groin flaps, and to find out whether it is still indicated in replacing damaged soft tissue of the hand in the era of microsurgery. METHODS: From 1982 to 2009, we treated 85 patients with soft tissue defects on the hand and distal forearm with pedicled groin flaps in our department and recorded them in a prospective database. We interviewed and examined 49 patients in this cohort. RESULTS: The mean age of the 85 patients was 33 years, the male/female ratio was 4:1, the mean hospital stay was 29 ± 13 days, and the mean follow-up was 9 years. The duration to flap division was 24 ± 5 days. Altogether, we performed a mean of 4.6 operations per patient, including thinning of the flap, deepening of the interdigital fold, and stump and flap revisions. One flap loss occurred. Of the 49 patients, results were mostly classified as good, and 82% of patients would undergo the procedure again. The mean Disabilities of the Arm, Shoulder, and Hand score value was 23 ± 17. The Vancouver Scar Scale showed nearly normal height and vascularity of the groin flap (0.2 ± 0.4 and 0.3 ± 0.6, respectively), pigmentation was slightly abnormal (0.8 ± 0.6), and pliability was evaluated between "supple" and "yielding" (1.5 ± 1.2). CONCLUSIONS: Results achieved with the groin flaps were positive. Most patients were satisfied with the results, and the operation was easily performed when McGregor's recommendations were followed. Nevertheless, considering the high number of secondary operations, the long hospital stay, and immobilization of the arm, groin flaps should be used only when free flaps or regional pedicle flaps are either not feasible or not indicated. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Influence of antiseptics on microcirculation after neuronal and receptor blockade.

The topical application of the antiseptics octenidine and polyhexanide on wounds seems to improve microcirculation. These two antiseptics were tested in combination with neuronal inhibition and sympathethic receptor blockade to verify these findings, explore the influence of ß blockers on these microcirculative effects, and find out the principle of operation. Investigations were carried out on a standardised cremaster muscle model in rats (n = 66). The tested antiseptics, octenidine and polyhexanide were investigated alone (n = 12) and in combination with bupivacaine (n = 12), metoprolol (n = 12), phentolamine (n = 12) and surgical denervation (n = 12). Physiological saline was used for control (n = 6). The arteriolar diameter and functional capillary density (FCD) were investigated via trans-illumination microscopy before, as well as 60 and 120 minutes after application. Polyhexanide caused a significant increase in arteriolar diameter (86·5 ± 3·8 µm versus 100·0 ± 3·6 µm) and, like octenidine (7·2 ± 0·7 n/0·22 mm(2) versus 11·6 ± 0·6 n/0·22 mm(2) ), in FCD (9·2 ± 0·5 versus 12·6 ± 0·9) as well. When the antiseptics are used in combination with bupivacaine, metoprolol, phentolamine or surgical sympathectomy, these effects were eliminated or inverted. Assessing the results of the different blockades in combination with polyhexanide, we surmise that the antiseptic polyhexanide acts on the microcirculation mainly by blocking α receptors. This study shows that polyhexanide and octenidine improve muscular perfusion. Interestingly, the benefit of polyhexanide and octenidine on muscular perfusion is eliminated when the antiseptics are combined with other vasoactive agents, especially ß blockers.

Long-term comparison of a routine laboratory parameter-based severity score with APACHE II and SAPS II.

BACKGROUND: Risk score models predicting mortality have tremendous value, but because of the additional effort involved, their clinical use remains low. The aim of this study is to compare three different scores that each requires different levels of effort during admission and throughout treatment: the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II (SAPS II), and the Dense Laboratory Whole Blood Applied Risk Estimation (DELAWARE) score. Of the three, only the DELAWARE is based solely on routine laboratory parameters. METHODS: Prospective data of the three scores were collected for 268 surgical patients admitted to the intensive care unit over 1 year. The predicted hospital mortality and survival were evaluated for the first 14 days. RESULTS: With a cutoff value of 0.65, the sensitivity of the DELAWARE was 71.6%, the specificity, 92.5%, and the correct classification rate, 87.3%. The APACHE II and SAPS II showed values of 41.2%/96.8%/86.2% and 62.7%/87.1%/82.5%, respectively. The r2 value was 0.884 for the DELAWARE, 0.876/0.814 for the APACHE II and SAPS II. Hospital mortality rate was overestimated by 20% to 65% in all scores. The discriminatory ability of the APACHE II and SAPS II increased throughout the course of treatment. CONCLUSIONS: The routine laboratory-based DELAWARE provides a reliable, valid risk assessment of the surgical intensive care patient at admission. It also provides additional information without added effort or poor interobserver reliability, which leads to better data comparability. We have to state that until now the data have been collected in a single-center and their general validity is therefore limited. By the end of treatment, the SAPS II and APACHE II had increased discriminatory ability and are therefore useful as process parameters.

Influence of topically applied antimicrobial agents on muscular microcirculation.

Bacterial infections cause major complications in wound healing. Local antiseptics are used for daily wound care; however, their potential toxic effects on the vasculature have not yet been thoroughly investigated. The aim of this study was to assess the effects of antiseptics on microcirculation. Investigations were performed on a standardized cremaster muscle model on rats (n = 60). The arteriolar diameter and functional capillary density (FCD) were investigated using transillumination microscopy before and 60 and 120 minutes after application of each of the following antimicrobial agents: alcohol, hydrogen peroxide, imipenem, octenidine dihydrochloride, polyhexanide, and ethacridine lactate. Although polyhexanide caused a significant arteriolar dilatation (106.25 ± 3.23 vs. 88.54 ± 6.74 µm [baseline value]) and increase of FCD compared with baseline value (12.65 ± 0.82 vs. 9.10 ± 0.50 n/0.22 mm), alcohol led to a significant decrease of both parameters (90.63 ± 10.80 vs. 52.09 ± 7.69 and 5.35 ± 0.54 vs. 1.68 ± 0.48) and was the only agent that caused arteriolar thrombosis. The FCD also increased significantly after treatment with hydrogen peroxide (10.55 ± 0.33 vs. 12.30 ± 0.48) and octenidine (6.82 ± 0.63 vs. 12.32 ± 0.63). However, no positive effect on arteriolar diameter could be found. Ethacridine lactate and imipenem did not impact either parameter. In addition to reducing bacteria, an antiseptic should be nontoxic, especially to the microcirculation. Polyhexanide seems to have a positive influence on vessel diameter and capillary density, whereas alcohol reduces both parameters. If the antimicrobial efficacy is comparable, the antiseptic with less toxic effects should be chosen, especially in critically perfused wounds.

Intravital pathophysiologic comparison of frostbite and burn injury in a murine model.

BACKGROUND: The breakdown of skin microcirculation and the leukocyte-endothelium interaction are assumed to play key roles in the pathophysiology of burn and frostbite injuries. Available data on frostbite and burn injuries were collected using different experimental models and setups, which limits direct comparisons of these thermal traumata significantly. To determine pathophysiologic similarities and differences, two comparable in vivo frostbite and burn models were used to assess microcirculatory and angiogenetic changes in burn and frostbite injuries. MATERIALS AND METHODS: Either deep partial thickness no-touch burns or frostbite injuries were inflicted to the ears of hairless mice (n = 40) by a hot or cold gas jet (117.0 ± 2.1°C for 1 s and -195.8 ± 2.7°C for 1.5 s, respectively) resulting in a necrotic, nonperfused area of about 1.56 ± 0.28 mm2. Intravital fluorescent microscopy was used in combination with fluorescent dyes in order to assess the microcirculation, angiogenesis, and leukocyte-activity over a 12-d period. RESULTS: The angiogenesis occurred significantly faster after frostbite than after burn (16.4% ± 4.5% versus 30.6% ± 2.8% nonperfused area, compared with the baseline value on d 7 (P = 0.009)). The loss of functional vessel density was significantly more pronounced after frostbite (57.6% ± 2.2% versus 89.2% ± 4.9% (P < 0.001)). However, the area recovered faster. The edema formation, as a parameter for endothelial integrity, was significantly more pronounced and lasted longer after frostbite, compared with the burn injury, and reached its maximum level on d 7 after trauma (162.4% ± 4.2% versus 142.% ± 5.9%; P = 0.007). In contrast to the rolling leukocytes, which showed the same increase on d 1 and then a subsequent decrease in both groups, the number of adherent leukocytes after the burn was markedly higher on d 1 (480% versus 167%; P = 0.001) but decreased much faster. The number of adherent leukocytes after frostbite remained significantly higher than those of the burn group during the entire observation. CONCLUSION: The comparison of analogous intravital burn and frostbite models indicates that despite the similarities, decisive microcirculatory differences in extension and recovery from these two types of thermal trauma exist.

Determination of microcirculatory changes and angiogenesis in a model of frostbite injury in vivo.

BACKGROUND: The breakdown of skin microcirculation and the leukocyte-endothelium interaction are assumed to play a key role in the pathophysiology of frostbite injuries. However, little is known as yet. The aim was to develop an in vivo frostbite model to monitor microcirculatory changes and angiogenesis after frostbite injury. MATERIALS AND METHODS: Deep partial thickness frostbite injuries were inflicted with a no-touch-technique to the ears of hairless mice (n=9). To this end, a gas jet of nitrogen vapor (T=-195,8±2.7°C) was delivered onto an area of 1.9 mm(2) for 1,5 s. Intravital fluorescent microscopy in combination with FITC-dextran and Rhodamin 6G as fluorescent dyes was used to assess microcirculatory changes, leukocyte behavior, and angiogenesis during the 14 d of wound healing. RESULTS: The area of no perfusion decreased significantly over the observed period, and perfusion was almost completely restored due to angiogenesis by d 14 (day 1: 1.89 [mm(2)]±0.44SEM, d 14: 0.02±0.01). No post-traumatic extension of the trauma could be observed. Edema formation increased significantly up to d 7. The number of adherent leukocytes showed a significant increase during the first 7 d. Functional vessel density showed a significant post-frostbite decrease to 60% of the baseline value. CONCLUSIONS: This novel frostbite model provides a simple and nonetheless highly effective technique of creating locally limited reproducible frostbite injuries using a no touch technique. Tissue damage can be fully attributed to the thermal trauma, and the model allows repetitive intravital fluorescent microscopy of the microcirculation, leukocyte-endothelium interaction, and angiogenesis.

Leiomyosarcoma of intravascular origin--a rare tumor entity: clinical pathological study of twelve cases.

BACKGROUND: Leiomysarcoma of intravascular origin is an exceedingly rare entity of malignant soft tissue tumors. They are most frequently encountered in the retroperitoneum arising from the inferior vena cava and are scarcely found to arise from vessels of the extremities. These tumors were analysed with particular reference to treatment outcome and prognosis. The aim of this article is to broaden the knowledge of the clinical course of this rare malignancy. METHOD: During 2000 and 2009 twelve patients were identified with an intravascular origin of a leiomyosarcoma. Details regarding the clinical course, follow-up and outcome were assessed with focus on patient survival, tumor relapse and metastases and treatment outcome. 3 year survival probability was calculated using Kaplan-Meier method. RESULTS: Vascular leiomyosarcomas accounted for 0.7% of all malignant soft tissue tumors treated at our soft tissue sarcoma reference center. The mean follow up period was 38 months. Tumor relapse was encountered in six patients. 6 patients developed metastatic disease. The three year survival was 57%. CONCLUSION: Vascular leiomysarcoma is a rare but aggressive tumor entity with a high rate of local recurrence and metastasis.

Synergistic effects of sonoporation and taurolidin/TRAIL on apoptosis in human fibrosarcoma.

Sonodynamic therapy, in combination with ultrasound contrast agents, proved to enhance the uptake of chemotherapeutics in malignant cells. HT1080 fibrosarcoma cells were treated in vitro with a combination of ultrasound SonoVue™-microbubbles and taurolidine (TRD) plus tumor necrosis factor related apoptosis inducing ligand (TRAIL). Apoptosis was measured by TdT-mediated dUTP-biotin nick end labelling (TUNEL) assay and fluorescence activated cell sorting (FACS) analysis. Gene expression was analysed by RNA-microarray. The apoptotic effects of TRD and TRAIL on human fibrosarcoma are enhanced by sonodynamic therapy and additional application of contrast agents, such as SonoVue™ by 25%. A broad change in the expression of genes related to apoptotic pathways is observed when ultrasound and microbubbles act synchronously in combination with the chemotherapeutics (e.g. BIRC3, NFKBIA and TNFAIP3). Some of these genes have already been proven to play a role in programmed cell death in human fibrosarcoma (HSPA1A/HSPA1B, APAF1, PAWR, SOCS2) or were associated with sonication induced apoptosis (CD44). Further studies are needed to explore the options of sonodynamic therapy on soft tissue sarcoma and its molecular mechanisms.

MFH revisited: outcome after surgical treatment of undifferentiated pleomorphic or not otherwise specified (NOS) sarcomas of the extremities -- an analysis of 140 patients.

BACKGROUND: Undifferentiated pleomorphic sarcoma/NOS (not otherwise specified; former pleomorphic and storiform MFH) of the extremities is a common malignant soft tissue tumor in adults. The objective of this study is to determine prognostic factors for the outcome after surgical treatment with respect to the recent developments in classification. METHODS: From 1996 to 2004, 140 undifferentiated pleomorphic sarcomas/NOS were identified out of 1,200 soft tissue sarcomas of the extremities that were treated at our institution and recorded in a prospective database. Overall survival (OS) and isolated local recurrence (ILR) were determined by Kaplan-Meier analysis. All tumors were retrospectively analyzed regarding prognostic factors of the disease, including patient's background (primary or recurrent), histological grade (G2/G3), adjuvant chemotherapy and radiotherapy, size (T1-2) and depth of the tumor, and surgical margins (R0, R1, R2). RESULTS: In 123 patients, a wide resection was performed (limb-sparing surgery). In nine patients, an amputation was necessary. The overall 5-year survival rate was 72% (median follow up: 52 months). There was a significant difference between the group presenting with primary tumors (5-year survival: 84%, p < 0.05) and recurrent tumors (5-year survival: 62%, p < 0.05). Isolated local recurrence occurred in 36 patients. CONCLUSIONS: In terms of OS and ILR, primary or recurrence, negative surgical margins, size and grading had a highly significant influence, whereas the site of surgery and adjuvant chemotherapy, adjuvant radiation and tumor depth did not. Prognosis for patients with undifferentiated pleomorphic sarcoma of the extremities depends predominantly on adequate wide resection of the primary tumor.

TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma.

BACKGROUND: Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080). METHODS: Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR. Protein level changes were documented by Western Blot analysis. NFKB activity was analysed by ELISA and proliferation assays (BrdU) were performed. RESULTS AND DISCUSSION: The single substances TRAIL and TRD induced apoptotic cell death and decreased proliferation in HT1080 cells significantly. Gene expression of several genes related to apoptotic pathways (TRAIL: ARHGDIA, NFKBIA, TNFAIP3; TRD: HSPA1A/B, NFKBIA, GADD45A, SGK, JUN, MAP3K14) was changed. The combination of TRD and TRAIL significantly increased apoptotic cell death compared to the single substances and lead to expression changes in a variety of genes (HSPA1A/B, NFKBIA, PPP1R15A, GADD45A, AXL, SGK, DUSP1, JUN, IRF1, MYC, BAG5, BIRC3). NFKB activity assay revealed an antipodal regulation of the several subunits of NFKB by TRD and TRD+TRAIL compared to TRAIL alone. CONCLUSION: TRD and TRAIL are effective to induce apoptosis and decrease proliferation in human fibrosarcoma. A variety of genes seems to be involved, pointing to the NFKB pathway as key regulator in TRD/TRAIL-mediated apoptosis.

Major and lethal complications of liposuction: a review of 72 cases in Germany between 1998 and 2002.

BACKGROUND: Liposuction is the most frequently performed cosmetic operation in Germany, with approximately 200,000 procedures performed in 2003. The public perception of liposuction as minor surgery fails to consider the potential of major complications or a possibly fatal outcome. METHODS: A retrospective analysis of severe or lethal complications related to cosmetic liposuction is presented. To collect pertinent information, the authors sent 3500 questionnaires to departments of pathology and forensic medicine, intensive care units, and others. After the identification of cases with major complications, the second phase of the investigation consisted of interviews with the physicians performing the liposuction. RESULTS: Two thousand two hundred seventy-five questionnaires (65 percent) were returned. The analyzed data showed 72 cases of severe complications, including 23 deaths following cosmetic liposuction in a 5-year period from 1998 to 2002. The most frequent complications were bacterial infections such as necrotizing fasciitis, gas gangrene, and different forms of sepsis. Further causes of lethal outcome were hemorrhages, perforation of abdominal viscera, and pulmonary embolism. Fifty-seven of 72 complications were clinically evident within the first 24 postoperative hours; 41 of these 72 liposuction procedures were performed using tumescent anesthesia and 17 of 72 were performed using true tumescent anesthesia, with four deaths. CONCLUSIONS: Major risk factors for the development of severe complications are insufficient standards of hygiene, the infiltration of multiple liters of wetting solution, permissive postoperative discharge, and selection of unfit patients. The lack of surgical experience was a notorious contributing factor, particularly regarding the timely identification of developing complications. This is in fact the first study reporting deaths related to liposuction performed entirely under true tumescent anesthesia.

A novel titanium wound chamber for the study of wound infections in pigs.

In the face of emerging multidrug-resistant microbes, reliable animal models are needed to study potential new therapies in infected wounds. To this end, we implanted screw-top titanium chambers subdermally in full-thickness wounds on both flanks (n = 6 per flank) of 2 Goettinger minipigs. After 1 wk, chambers were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, or vehicle only. Throughout the study, wound fluid was harvested for quantitative bacterial cultures to monitor infection. Animals were followed for 4 wk, after which tissue biopsies were taken for histologic analysis and quantitative bacterial counts. The implanted titanium chambers were well tolerated by the pigs throughout the study. After inoculation of the chambers, wound infection was established and maintained for 14 d. Despite infection, no systemic effects were noted. Cross-contamination was negligible, compared with the vehicle-only control. After tissue ingrowth, each chamber creates a closed system that allows harvest of exudate or application of substances without loss of material from the chamber. Because 12 chambers are implanted in each pig, researchers have the opportunity to compare multiple treatment options (for example, antibiotics, antimicrobial peptides, gene therapy) in the same animal, with no interindividual variation. We conclude that the use of titanium chambers in pigs provides a reliable and reproducible in vivo model to investigate wound healing, wound infection, and treatment options.

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-alpha 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.

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.

Prognostic significance of erythroblasts in burns.

Changes in hematopoiesis that occur in humans after a burn injury may have important effects on morbidity and mortality. In patients with a variety of severe diseases, the presence of erythroblasts in peripheral blood is known to be indicative of a poor prognosis. However, the prognostic significance of erythroblasts in peripheral blood of burn patients has not yet been estimated. This study included 464 consecutive burn patients, of whom 81 did not survive their injuries (17.5 percent). Together with erythroblasts in blood, data on age, sex, total burn surface area, third-degree burn, inhalation trauma, white blood cell count, C-reactive protein, and hemoglobin were studied. The mortality rate of patients with erythroblasts in peripheral blood (n = 53) amounted to 56.6 percent (n = 30; total burn surface area, 39 percent), which is significantly higher (p < 0.001) than the mortality rate of patients without erythroblasts (12.4 percent, n = 51; total burn surface area, 18.69 percent). None of the 10 patients with more than 1000 erythroblasts x 10/liter survived. The detection of erythroblasts in the peripheral blood of burn patients is highly predictive of death, with the odds ratio after adjustment for the other known prognostic factors being 8.3 (95 percent confidence interval, 4.5 to 15.3). Erythroblasts were detected for the first time on average 10 +/- 4 days (median, 6 days) after admission and 13 +/- 6 days (median, 7 days) before death. Detection of erythroblasts in burn patients is of high prognostic power with regard to in-hospital mortality, providing physicians with a strong prognostic method with which to identify seriously threatened patients. It seems attractive to think about an incorporation of erythroblasts into further refinements of burn scores.

Fournier's gangrene after Milligan-Morgan hemorrhoidectomy requiring subsequent abdominoperineal resection of the rectum: report of a case.

The development of Fournier's gangrene after Milligan-Morgan hemorrhoidectomy of a previously healthy 76-year-old female patient is described. After such a common surgical procedure, the patient developed full-thickness skin necrosis of the perianal region including the rectum. Immediate radical debridement was mandatory. Because of rectal involvement, a diverting sigmoid colostomy was required. The rectum had to be removed by abdominoperineal resection. This disastrous complication was completely unexpected and unpredictable after Milligan-Morgan hemorrhoidectomy because of the lack of predisposing factors.

Effects of desmopressin on thrombogenesis in aspirin-induced platelet dysfunction.

Aspirin causes a coagulation disorder. Desmopressin has haemostatic effects by increasing the plasma levels of coagulation factor VIII and von Willebrand factor. The precise effects of desmopressin on thrombogenesis are not known. In an in vivo model, we investigated the effect of the drug on thrombus formation and platelet function after aspirin use. Male Lewis rats weighing 250-300 g were used. Four groups with 10 animals each were formed: control, aspirin, desmopressin and aspirin + desmopressin. In each animal, the femoral artery was dissected. A thrombogenic vessel injury was created by inverting a full thickness portion of the proximal edge of the incised artery into the lumen. The following parameters were measured: maximum thrombus size, time period until maximum thrombus size was reached and overall platelet function. In addition, the thrombi generated were investigated histologically. Thrombus formation time was significantly shorter with desmopressin compared with the animals treated with aspirin (P < 0.0001) and controls (P = 0.008). Maximum thrombus size was larger in the desmopressin and desmopressin + aspirin groups when compared with the group treated with aspirin only. Overall platelet function was significantly enhanced with desmopressin compared with controls (P = 0.025) and with aspirin (P < 0.0001). The differences were confirmed histologically. In conclusion, desmopressin significantly accelerates thrombus formation in aspirin-treated animals. It can also re-establish thrombus size after the use of aspirin. Overall platelet function is significantly increased by desmopressin.