H.-H. Homann

Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides.

BackgroundThe antibacterial activity of host defense peptides (HDP) is largely mediated by permeabilization of bacterial membranes. The lipid membrane of enveloped viruses might also be a target of antimicrobial peptides. Therefore, we screened a panel of naturally occurring HDPs representing different classes for inhibition of early, Env-independent steps in the HIV replication cycle. A lentiviral vector-based screening assay was used to determine the inhibitory effect of HDPs on early steps in the replication cycle and on cell metabolism.ResultsHuman LL37 and porcine Protegrin-1 specifically reduced lentiviral vector infectivity, whereas the reduction of luciferase activities observed at high concentrations of the other HDPs is primarily due to modulation of cellular activity and/ or cytotoxicity rather than antiviral activity. A retroviral vector was inhibited by LL37 and Protegrin-1 to similar extent, while no specific inhibition of adenoviral vector mediated gene transfer was observed. Specific inhibitory effects of Protegrin-1 were confirmed for wild type HIV-1.ConclusionAlthough Protegrin-1 apparently inhibits an early step in the HIV-replication cycle, cytotoxic effects might limit its use as an antiviral agent unless the specificity for the virus can be improved.

Resektionsmethodik und funktionelle Wiederherstellung bei Weichgewebesarkomen der Extremitäten

Abstract. In soft tissue sarcoma of the extremities wide tumor excision (R0) has become the most important factor for local control. The tactical and technical surgical parameters are defined, which allow for diminished complication rates during tumor biopsy and definite resection. Reconstructive plastic procedures play a key role in coverage of maior defects and prevention of problems due to wound infection and irradiation. If localized within the periphery of limbs, the vast majority of cases will require sophisticated techniques to achieve limb salvage.Zusammenfassung. Bei Weichgewebesarkomen der Extremitäten stellt die weite Excision in sano (R0) den wichtigsten Parameter zur Verhütung eines Lokalrezidivs dar. Es werden die taktischen und technischen Parameter beschrieben und diskutiert, die bei Biopsie und definitiver Tumorresektion die lokalen Komplikationsraten senken. Plastisch rekonstruktive Methoden erlauben dabei die Deckung ausgedehnter onkologischer Defekte, und reduzieren Infekt- sowie radiogene Schäden. In der Extremitätenperipherie gelingt die Gliedmaßenerhaltung in mehr als der Hälfte der Fälle nur mit Hilfe dieser Techniken.

A liposome hydrogel with polyvinyl-pyrrolidone iodine in the local treatment of partial-thickness burn wounds.

Local treatment of burn injuries with conventional anti-infective preparations does not provide the moist environment that promotes fast wound healing. In a randomized controlled trial the effects of liposome polyvinyl-pyrrolidone-iodine (PVP-I) hydrogel, a novel formulation of PVP-I in a liposome hydrogel with high water-binding capacity, were investigated in 43 patients with partial-thickness burn wounds in an intraindividual comparison with a conventional silver-sulfadiazine cream. Treatment with liposome PVP-I hydrogel resulted in significantly faster complete healing of the burn wounds compared with silver-sulfadiazine cream (9.9 ± 4.5 days versus 11.3 ± 4.9; P < 0.015). The cosmetic result (smoothness, elasticity, appearance) was rated as excellent for 37.0% of study wounds with liposome PVP-I hydrogel compared with 13.0% of wounds treated with silver-sulfadiazine cream. Local tolerability was good; handling and change of dressing were rated as easy. Local treatment with liposome PVP-I hydrogel thus provides fast wound healing with a favorable cosmetic result.

[Importance of specialized centers in diagnosis and treatment of extremity-soft tissue sarcomas. Review of 603 cases].

ZusammenfassungDie onkologiegerechte Therapie maligner Weichgewebstumoren setzt eine korrekte Diagnosestellung inklusive Angabe des Gradings voraus. Aufgrund der Seltenheit dieser Tumoren, einer Vielzahl verschiedener Subtypen, dem teilweise uneinheitlichen histologischen Erscheinungsbild und nicht repräsentativen Biopsiepräparaten ist diese Klassifikation oft erschwert.Sechshundertdrei konsekutive Patientenakten mit der Diagnose „maligner Weichgewebstumor“ der Extremitäten inklusive Schulter und Glutealbereich wurden im Hinblick auf Diagnoseabweichungen der Primär- und Referenzpathologie sowie deren Abhängigkeit von der Tumorentität, der Befundung aus Primär- oder Rezidivtumor und der beurteilenden pathologischen Einrichtung ausgewertet. Als referenzpathologische Institute dienten das auf Weichgewebstumoren spezialisierte Institut für Pathologie der Ruhr-Universität Bochum am BG-Universitätsklinikum Bergmannsheil in Kooperation mit dem Institut für Pathologie der Universität Jena.Liposarkome und pleomorphe („not otherwise specified“, NOS-)Sarkome stellten mit 24 und 22,6% die größten Gruppen. Von den acht am häufigsten diagnostizierten Sarkomen wurden maligne periphere Nervenscheidentumoren und Leiomyosarkome mit 78,4 und 74,2% der Fälle am häufigsten diskordant diagnostiziert. Die Quote lag für nicht spezialisierte Pathologiepraxen und Einrichtungen an Allgemein- und Universitätskrankenhäusern über 60%. Für eine individuelle, adäquate chirurgische und neo-/adjuvante Therapie ist die referenzpathologische Begutachtung sarkomverdächtiger Tumorproben zu fordern.AbstractCorrect histopathologic diagnosis is essential for adequate treatment of soft tissue sarcomas. Due to the disorder’s rarity, multitude of subgroups, sometimes varying histopathologic appearance, and occasionally inadequate biopsy specimens, diagnosis and grading are challenging. The records of 603 patients with soft tissue tumors of the extremities were reviewed concerning mismatches in primary and definite diagnoses relating to entity, evaluation of primary or recurrent tumor specimens, and the diagnosing pathology institution. For second opinions we referred to the Institute of Pathology of the Ruhr University at the Bergmannsheil Hospital in Bochum, Germany, and to the Pathology Institute of the University of Jena, also in Germany. Liposarcoma and malignant fibrous histiocytoma were the most often diagnosed subgroups at 24% and 22.6%, respectively. In the eight most frequent sarcoma types, malignant peripheral nerve sheath tumors and leiomyosarcoma had the highest rates of false primary diagnosis, 78.4% and 74.2% of cases, respectively. The diagnostic error ratio for nonspecialized pathologists in practice, community hospital pathologists, and academic medical centers was over 60%. For optimal treatment of soft tissue sarcomas, we suggest obtaining expert second opinion to ensure adequate surgical therapy and precise indications for radiation and chemotherapy.Correct histopathologic diagnosis is essential for adequate treatment of soft tissue sarcomas. Due to the disorders rarity, multitude of subgroups, sometimes varying histopathologic appearance, and occasionally inadequate biopsy specimens, diagnosis and grading are challenging. The records of 603 patients with soft tissue tumors of the extremities were reviewed concerning mismatches in primary and definite diagnoses relating to entity, evaluation of primary or recurrent tumor specimens, and the diagnosing pathology institution. For second opinions we referred to the Institute of Pathology of the Ruhr University at the Bergmannsheil Hospital in Bochum, Germany, and to the Pathology Institute of the University of Jena, also in Germany. Liposarcoma and malignant fibrous histiocytoma were the most often diagnosed subgroups at 24% and 22.6%, respectively. In the eight most frequent sarcoma types, malignant peripheral nerve sheath tumors and leiomyosarcoma had the highest rates of false primary diagnosis, 78.4% and 74.2% of cases, respectively. The diagnostic error ratio for nonspecialized pathologists in practice, community hospital pathologists, and academic medical centers was over 60%. For optimal treatment of soft tissue sarcomas, we suggest obtaining expert second opinion to ensure adequate surgical therapy and precise indications for radiation and chemotherapy.

The pedicled gastrocnemius muscle flap: a review of 218 cases.

Background: Data regarding donor-site morbidity, postoperative clinical course, and functional and aesthetic outcome after gastrocnemius muscle flaps are rare. Methods: Data regarding 218 consecutive patients treated with gastrocnemius muscle flaps were acquired from patients’ charts and from contact with patients, with special reference to treatment and clinical course. Eighty-two were interviewed with a standardized questionnaire, 40 were examined physically, and 34 underwent dynamometric muscle function tests. Results: The authors observed wound-healing difficulties in 7 percent, wound infections in 4 percent, and one flap loss; 4.5 percent of the lateral gastrocnemius patients suffered from postoperative palsy of the peroneal nerve. Eighty-seven percent were not significantly limited walking on even ground, but only 42 percent could run, and 40 percent complained about pain when walking more than 200 m. The average range-of-motion deficit in the ankle joint for flexion and extension was 11 percent and 10 percent, respectively. The maximal plantar flexion force in the ankle joint of the operated leg was 76.2 percent. Strength endurance was reduced approximately 24.4 percent in the operated leg compared with the nonaffected side. Conclusions: Gastrocnemius muscle transfer represents a safe and simple procedure in the treatment of lower leg defects and in limb preservation. The strength loss and functional impairment (and sensation disorders) are considerable but may not be exclusively attributable to the muscle transfer but rather the result of the preceding trauma, infection, or tumor resection. The donor-site morbidity is well tolerated by the majority of the patients.

Current indications for glycerol-preserved allografts in the treatment of burn injuries

Current indications for glycerol-preserved allografts in the treatment of burn injuries D. Druecke a,∗, L. Steinstraesser a, H.H. Homann a, H.U. Steinau a, P.M. Vogt b a Department of Plastic Surgery, Burn Center, University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany b Department of Plastic Surgery, Burn Center, University Hospital Oststadt-Krankenhaus, University Hannover, Hannover, Germany

Die Bedeutung von Referenzzentren in Diagnose und Therapie von Weichgewebssarkomen der Extremitäten

ZusammenfassungDie onkologiegerechte Therapie maligner Weichgewebstumoren setzt eine korrekte Diagnosestellung inklusive Angabe des Gradings voraus. Aufgrund der Seltenheit dieser Tumoren, einer Vielzahl verschiedener Subtypen, dem teilweise uneinheitlichen histologischen Erscheinungsbild und nicht repräsentativen Biopsiepräparaten ist diese Klassifikation oft erschwert.Sechshundertdrei konsekutive Patientenakten mit der Diagnose „maligner Weichgewebstumor“ der Extremitäten inklusive Schulter und Glutealbereich wurden im Hinblick auf Diagnoseabweichungen der Primär- und Referenzpathologie sowie deren Abhängigkeit von der Tumorentität, der Befundung aus Primär- oder Rezidivtumor und der beurteilenden pathologischen Einrichtung ausgewertet. Als referenzpathologische Institute dienten das auf Weichgewebstumoren spezialisierte Institut für Pathologie der Ruhr-Universität Bochum am BG-Universitätsklinikum Bergmannsheil in Kooperation mit dem Institut für Pathologie der Universität Jena.Liposarkome und pleomorphe („not otherwise specified“, NOS-)Sarkome stellten mit 24 und 22,6% die größten Gruppen. Von den acht am häufigsten diagnostizierten Sarkomen wurden maligne periphere Nervenscheidentumoren und Leiomyosarkome mit 78,4 und 74,2% der Fälle am häufigsten diskordant diagnostiziert. Die Quote lag für nicht spezialisierte Pathologiepraxen und Einrichtungen an Allgemein- und Universitätskrankenhäusern über 60%. Für eine individuelle, adäquate chirurgische und neo-/adjuvante Therapie ist die referenzpathologische Begutachtung sarkomverdächtiger Tumorproben zu fordern.AbstractCorrect histopathologic diagnosis is essential for adequate treatment of soft tissue sarcomas. Due to the disorder’s rarity, multitude of subgroups, sometimes varying histopathologic appearance, and occasionally inadequate biopsy specimens, diagnosis and grading are challenging. The records of 603 patients with soft tissue tumors of the extremities were reviewed concerning mismatches in primary and definite diagnoses relating to entity, evaluation of primary or recurrent tumor specimens, and the diagnosing pathology institution. For second opinions we referred to the Institute of Pathology of the Ruhr University at the Bergmannsheil Hospital in Bochum, Germany, and to the Pathology Institute of the University of Jena, also in Germany. Liposarcoma and malignant fibrous histiocytoma were the most often diagnosed subgroups at 24% and 22.6%, respectively. In the eight most frequent sarcoma types, malignant peripheral nerve sheath tumors and leiomyosarcoma had the highest rates of false primary diagnosis, 78.4% and 74.2% of cases, respectively. The diagnostic error ratio for nonspecialized pathologists in practice, community hospital pathologists, and academic medical centers was over 60%. For optimal treatment of soft tissue sarcomas, we suggest obtaining expert second opinion to ensure adequate surgical therapy and precise indications for radiation and chemotherapy.Correct histopathologic diagnosis is essential for adequate treatment of soft tissue sarcomas. Due to the disorders rarity, multitude of subgroups, sometimes varying histopathologic appearance, and occasionally inadequate biopsy specimens, diagnosis and grading are challenging. The records of 603 patients with soft tissue tumors of the extremities were reviewed concerning mismatches in primary and definite diagnoses relating to entity, evaluation of primary or recurrent tumor specimens, and the diagnosing pathology institution. For second opinions we referred to the Institute of Pathology of the Ruhr University at the Bergmannsheil Hospital in Bochum, Germany, and to the Pathology Institute of the University of Jena, also in Germany. Liposarcoma and malignant fibrous histiocytoma were the most often diagnosed subgroups at 24% and 22.6%, respectively. In the eight most frequent sarcoma types, malignant peripheral nerve sheath tumors and leiomyosarcoma had the highest rates of false primary diagnosis, 78.4% and 74.2% of cases, respectively. The diagnostic error ratio for nonspecialized pathologists in practice, community hospital pathologists, and academic medical centers was over 60%. For optimal treatment of soft tissue sarcomas, we suggest obtaining expert second opinion to ensure adequate surgical therapy and precise indications for radiation and chemotherapy.

Polybrene improves transfection efficacy of recombinant replication‐deficient adenovirus in cutaneous cells and burned skin

The hostile environment found in acute and chronic wounds decreases the physiological half‐life of purified synthetic or recombinant peptides dramatically. Gene therapy, on the other hand, may be a viable option since it relies on the cellular machinery of the host to locally manufacture the proteins of interest. The aim of this study was to evaluate and optimize the local administration of transient cutaneous adenoviral gene delivery in wounds.

Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures.

Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique. A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as TRAIL Receptor2, CDKN1A, GADD45A, FAS, CD40, PAWR, NFKBIA, IER3, PSEN1, RIPK2, and CD44. The anti-apoptotic genes TNFAIP3, PEA15, Bcl2A1, NGFB, and BIRC3 were also up-regulated. The pro-apoptotic CD14, TIA1, and ITGB2 were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic YWHAH. Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.

[Wound healing complications in smokers, non-smokers and after abstinence from smoking].

BACKGROUND The pulmonary and cardiovascular ramifications of smoking are well documented and this also applies to increased wound healing complications in smokers. The aim of this study was to ascertain whether preoperatively refraining from smoking would affect the incidence of wound healing disorders. MATERIAL AND METHODS Between 2006 and 2008 a total of 295 patients underwent aesthetic (n = 167) or reconstructive surgery (n = 128). They were divided into three groups: A (n = 98) non-smokers for at least 2 years, B (n = 99) patients who refrained from smoking 6 weeks prior to surgery and C (n = 98) smokers. Smoking abstinence was verified by cotinine tests. Wound healing complications were defined as dehiscent wounds, wound infections, atypical scar formation and adiponecrosis. RESULTS Smokers developed wound healing complications in 48.2% of cases, non-smokers in 21.0% and patients who had stopped smoking for 6 weeks in 30.8% of cases (p = 0.006). CONCLUSION Elective surgery should only be performed on non-smokers and smokers who had refrained from smoking for at least 6 weeks to reduce wound healing complications as far as possible.