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Biomedical subjects

M Lehnhardt

Publications and source records attributed to M Lehnhardt.

At least 19 recordsLinked to original sources

Activity of histone H1.2 in infected burn wounds.

OBJECTIVES: Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity. METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria. RESULTS: Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control. CONCLUSIONS: These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.

Animals↗

A qualitative and quantitative analysis of protein loss in human burn wounds.

INTRODUCTION: It is well known that in patients suffering from major burn injuries of more than 15% of total body surface area (TBSA), capillary leak and loss of proteins including immunoglobulins (Ig) lead to cardiovascular failure and significantly elevated risk of infections. However, knowledge of the resulting protein profiles is limited. In order to elucidate quantitative and qualitative protein loss in human burn wounds we compared wound fluid (WF) protein content with serum protein levels. MATERIAL AND METHODS: Eleven patients suffering from second degree burns of 18-68% TBSA were enrolled in the study. Immediately after admission burn wounds were enclosed in cutaneous vinyl wound chambers covering a 2.25 cm(2) wound surface area. WF and serum samples were harvested every 8 h with a follow up of 48 h and analyzed for total protein content, albumin and the immunoglobulins A, E, G and M. RESULTS: Protein levels in serum were significantly lower as compared to physiological levels while WF protein levels were elevated and remained high. Total protein (TP) and albumin (AL) accumulated in high concentrations on the wound surface (average accumulation on 10% burnt TBSA within 8 h: TP=16.59+/-8.86 g; AL=12.39+/-5.87 g). The albumin fraction in WF showed increasing values (24 h: 69%; 32 h: 86%) although the serum albumin fraction remained nearly unchanged (55%). Peak values were initially found for all immunoglobulins both in serum and WF. IgA, E and M reached a steady state 32 h post-trauma, whereas IgG continuously decreased until 40 h. IgG values in serum were significantly below physiological levels at all time points. CONCLUSIONS: This study qualifies and quantifies a significant protein loss in second degree burn wounds. Protein concentrations in wound fluid correlate highly with serum concentrations until 48 h post-burn. A patient's entire amount of serum proteins accumulates in wound fluid in a 20% TBSA burn within approximately 24h. In contrast to capillary leak theory proteins and immunoglobulins extravasate to wound fluid even after 48 h post-trauma.

Adult↗

Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP-18/LL-37 is effective for the treatment of burn wound infections.

Host defense peptides (HDP) are naturally occurring effector molecules of the innate immune system, which might be an alternative to currently used antibiotics. The objective of this study was to investigate the efficiency of transient cutaneous adenoviral transfection with human cathelicidin hCAP-18/LL-37 in infected burn wounds. Specific transgene expression was analyzed in vitro on mRNA and protein level using real-time PCR and Western-blot. Male Sprague-Dawley rats (n=40) received a second degree scald burn on both flanks (5% BSA), which were inoculated with 10(8) colony-forming units (CFU) Pseudomonas aeruginosa. Two days later, rats were randomized into the following groups: (1) adenoviral delivery of LL-37 (Ad5-hCAP-18, n=10), (2) synthetic host defense peptide LL-37 (1 mg; n=10), (3) carrier control (PBS, n=10) and (4) empty-virus control (Ad5-LacZ, n=10). Agents were injected intradermally and subcutaneously into both flanks. After either 2 or 7 days, skin samples were harvested and homogenized. CFU per gram tissue were determined. The hCAP-18/LL-37 expression was confirmed by real-time PCR and localized using in situ hybridization. In vitro transfection of cutaneous cells delivered a specific response on mRNA production. Western blot analysis revealed protein expression of hCAP-18/LL-37 in conditioned medium and cell pellet. The host defense peptide LL-37 was detectable after cleavage of the inactive pro-form hCAP-18/LL-37 with human elastase. Ad5-hCAP-18 showed a significant bacterial inhibition of approximately 10 000 fold compared to the control group (P<0.001) and 1000-fold (P<0.001) compared to the synthetic HDP LL-37 7 post-transfection. No inhibition was observed for the carrier or empty-virus control. Real-time PCR and in situ hybridization confirmed expression of hCAP-18/LL-37. In conclusion, transient cutaneous adenoviral delivery of the host defense peptide hCAP-18/LL-37 is significantly more effective than administration of synthetic host defense peptides and might be a potential adjunct for wound treatment in the near future.

Adenoviridae↗

[Serious complications of injections--retrospective analysis of incidences, complication-management, prophylaxis and economic aspects].

The parenteral drug application is a routinely used method in all medical disciplines. Intramuscular, intraarticular, intravenous injections and infusions can cause local complications such as abscesses, articular infections or paravasates. These local complications can lead to bacteraemia, sepsis and may lead to multiple organ failure associated with high morbidity and mortality. Although these complications are rare, they are sometimes disastrous and result in life threatening clinical conditions. During a retrospective analysis (review period 1998-2002) 24 patients were admitted and hospitalized in our department. Within this report we demonstrate 7 patients with fatal complications after injections. In the majority of cases minor patients' complaints were proceeding before major complications were present. A long and expensive treatment period with multiple surgical interventions ends up in functional disabilities and unsatisfactory aesthetic results. Instead of delayed surgical treatment immediate radical surgical care is crucial to prevent disastrous complications. In case of the inability of sufficient debridement, amputations are sometimes indicated in the sense of "life before limb". Besides the consequences for the patient these disastrous complications have a high socioeconomic impact and result in reduced reimbursement for the hospital stay.

Abscess↗

[The anatomy of the surgical treatment of migraine].

OBJECTIVE: The transpalpebral resection of the corrugator and depressor supercilii muscles is a new treatment option for migraine headaches. Hyperactive contractility of these muscles can provoke the peripheral compression of the supratrochlear nerve and induce a neurogenic inflammation triggering the symptoms of migraine. In order to gather detailed knowledge of the respective anatomy in the eyebrow region, a macroscopic cadaver study was conducted. MATERIALS AND METHODS: The relevant muscles of the forehead, glabella and eyebrow were dissected in five fresh, non-preserved heads. The supracanthal origins and dermal points of insertion were marked. Following the preparation of the neurovascular structures, the muscles were measured and weighed. The course of the supraorbital and supratrochlear nerves was demonstrated from the forehead to the orbital cavity. RESULTS: There are three, paired groups of muscles in the superomedial region of the orbital rim. They can be divided into the superficial frontalis and procerus muscle, the orbicularis muscle in a middle layer and the corrugator and depressor supercilii in a deeper layer. The corrugator measured approximately 4.5 cm, whose origin is superior and posterior to the depressor origin situated cranial to the medial canthus. The corrugator inserts lateral to the exit of the supraorbital nerve in the dermis above the eyebrow after penetrating the orbicularis and frontalis muscles and a subgaleal fat pad. The length and weight of the muscles is highly variable. The muscle is penetrated by the supratrochlear nerve whereas the supraorbital nerve runs underneath it. The corrugator is innervated medially and laterally by branches of the facial nerve. CONCLUSION: A detailed knowledge of the complex arrangement of the muscles acting upon the glabella and the different communicating subgaleal and preseptal fat pads allow the identification and resection of the corrugator and depressor muscles without damaging the supratrochlear nerve. The course of the specific nerves is variable. The double-innervation of the corrugator suggests its complete resection instead of the selective denervation of the muscle.

Cadaver↗

[The interdisciplinary approach in reconstructive surgery of the extremities].

In cases of extended post-traumatic soft-tissue and bone loss as well as with mutilating infection or radical tumor resection, multidisciplinary options are required to salvage extremities and functional rehabilitation. A surgical team approach allows for reduction of amputation rates, wound healing complications, and secondary procedures in limb oncology and trauma. The goals and limitations of cooperative surgical concepts are described. In the future, continuing medical education will focus not only on indications and techniques but also on complication management, medicolegal problems, and economic deficits due to maladapted legal structures. Provided clear clinical pathways are introduced to guide indications, surgical procedures, and postoperative treatment, marked financial deficits may be avoided. While, in the past, responsibility for the patient and ethical considerations resulted in the development of voluntary interdisciplinary treatment programs, economic strategies and an increasing number of malpractice suits will inevitably produce new imperatives for interdisciplinary cooperation in the future.

Adult↗

[Liposarcoma of the extremities: recent developments in surgical therapy--analysis of 167 patients].

Liposarcoma is the second most common malignant soft-tissue tumor in adults. Between 1991 and 2002, 167 patients with extremity liposarcomas were treated in our center. Fifty tumors were classified as G1 liposarcomas (30%), 76 as G2 liposarcomas (45.5%), and 41 as G3 liposarcomas (24.5%). In 158 patients, (93.5%) wide tumor excision was performed. Major amputation was necessary in five patients. After a median follow-up of 36 months, 37 patients had developed local recurrence. The 5-year overall survival rate was 79%. The 5-year survival rate in primary tumors was 71/79 (90%, P<0.05) whereas 61/88 of recurrences relapsed locally (69%, P<0.05). Multidisciplinary cooperation in a tumor board is a precondition for adequate treatment.

Adult↗

[liposarcoma. Aspects of pathomorphology--an analysis of 209 tumos].

BACKGROUND: Among the heterogeneous group of adult soft tissue sarcomas, liposarcomas represent the largest entity along with malignant fibrous histiocytomas (MFH). PATIENTS AND METHODS: This article summarizes the results of pathomorphological data on 209 liposarcomas resected over a 10-year period. RESULTS: The most common tumor site was the thigh, and the peak age incidence was in the 5th and 6th decades. In general, three major subtypes of liposarcoma can be distinguished in terms of pathomorphology: well-differentiated/dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Well-differentiated liposarcomas represent malignancy grade 1 tumors without biological potential to metastasize, but which are able to relapse locally in cases of incomplete resection. When a local relapse has occurred, the liposarcoma may show dedifferentiation and may metastasize. CONCLUSIONS: In the pathologic-anatomical diagnosis of liposarcomas, conventional light-microscopic findings are decisive. Additional methods of molecular pathology may help in single cases to gain further insights.

Adult↗

[Therapy-induced tumor regression in adult soft tissue sarcomas-morphological findings].

Morphological findings of 21 soft tissue sarcomas of adulthood following preoperative chemo- and/or radiotherapy including perfusion therapy and resection are presented. The therapy-induced changes included a spectrum ranging from total tumor regression up to still completely vital tumor (median of all cases: 30% vital tumor tissue). 7 of 21 sarcomas (33%) were evaluated as responders (grade I-III). So-called malignant fibrous histiocytoma (MFH) revealed a good tumor response to preoperatively administered therapy (regression grades I and II). Myxoid/round-cell liposarcoma exhibited regression grades of IV-V (i.e. 30% up to 95% vital tumor tissue, non-responders). Synovial sarcoma was characterized by regression grades III up to VI (i.e. up to 100% vital tumor tissue without any signs of regression, 83% non-responders). Completely vital tumor was evident in 2 synovial sarcomas despite preoperative tumor therapy. These findings hint towards differences in response of distinct sarcoma entities to preoperative chemo-/radiotherapy. A grading of therapy-induced tumor regression in adult soft tissue sarcomas may best refer to already established grading schemes (e.g. according to the grading scheme for osteosarcomas following chemotherapy of Salzer-Kuntschik). A report of sarcoma resection specimens should include the percentage of vital tumor tissue.

Adult↗

[Gorham-Stout disease: report of a case affecting the right hand with a follow-up of 24 years].

Gorham-Stout disease is a rare idiopathic syndrome with distinctive clinical, pathologic and radiologic features. It is a variant form of osseus angiomatosis associated with massive osteolysis of bone. Usually appearing after trauma, the disease is described to occur at any age. Especially in case of thoracic involvement (chylothorax), lethal outcomes are reported. In Medline, about 200 cases have been described. A patient with osteolysis of the right hand following contusion at the age of two years is reported. Despite radiotherapy and repeated bone grafting, the osteolysis progressed until today (24 years). The pathologic features and various treatment methods for hand involvement are discussed.

Adult↗

[No problem with liposuction?].

Subcutaneous liposuction in tumescent technique is the most frequent aesthetic plastic procedure in the United States. In Germany, nearly 250,000 liposuctions are done per year by a variety of surgical and nonsurgical specialists including plastic surgeons, dermatologists, gynecologists, oral surgeons, and otolaryngologists in settings ranging from hospital operating rooms to physicians' offices. The method is applied and promoted as an easy-to-learn technique that is suited as an outpatient procedure. Although major complications seem to be rare, there are definite risks, including death at a rate of 1/5,000 procedures. Major risk factors are insufficient hygiene standards, multiliter wetting solution infiltration, megavolume aspiration, multiple cosmetic procedures in one setting, sedative and anesthetic drug hangover threatening ventilation, permissive postoperative discharge, and mistakes in patient selection. When major complications occur, office-based practitioners may refer patients to hospital emergency departments, where medical personnel unfamiliar with this procedure may underestimate the risk of major complications.

Adult↗

[Solitary plasmacytoma of the shoulder. Diagnosis and therapeutic methods].

5% of all multiple myelomas manifest as solitary plasmocytomas. The multiple myeloma is the most frequent malignant transformation of the haematopoetic system, with an incidence of 2:100,000 per year. 1% of all solitary plasmocytomas are found in the extremities, accounting for less than one case per year in Germany. In this article we present the case of a fifty year old patient with a solitary plasmocytoma of the shoulder region and discuss the diagnostic and therapeutic procedures involved.

Diagnosis, Differential↗

[Carl von Reyher's studies of wound therapy].

Carl von Reyher (1846-1890), a young Russian army surgeon of the late nineteenth century, established the principle of repeated debridements on a scientific basis. After a visit to Lister's clinic, acquainting himself with antiseptic wound management, von Reyher was the first to present a controlled study of debridement in contaminated gunshot wounds. He was able to show that the combination of primary debridement and antiseptic treatment decreased the mortality rate of gunshot injuries from 66% to 23%. Although published in more than 16 papers and presented at international congresses, Reyher's contribution was completely negated. Finally more than 30 years later in World War I, the Inter-allied Surgical Conference officially endorsed primary excision with delayed wound closure as the rule for treatment of gunshot wounds.

Antisepsis↗

[Secondary reconstruction after burns of the anogenital area].

The incidence of burns of the genitalia and peri-anal region which may cause a reconstructive intervention is very low. In the most cases the use of split thickness skin grafts yields a sufficient permanent wound closure. Upcoming problems such as painful scare formation require a reconstructive intervention (Z-plasty, full thickness skin grafting, pedicled flaps etc.). In case that the anal sphincter is involved with the consequence of incontinence or major damage of the genitalia occurred, sophisticated operative solutions are necessary.

Anal Canal↗

[Joint infection caused by radiogenic defect: prevention and therapeutic options].

Exposed irradiated joints are characterized by bone and cartilage necrosis with a chronically infected joint space. The indication for treatment results from possible infection spreading and more often because of severe pain. The usual concept of sequential debridement, joint replacement and regional flap coverage, is often impossible due to the radiodermitis and bone necrosis in the neighbourhood of the joint. Even free flaps are associated with a higher failure rate, because of the irradiation of the recipient vessels long vein grafts are often needed. If regional flap coverage is desired, distant flaps with long, not irradiated pedicles must be chosen. Prevention due to special considerations during the first surgery is essential.

Amputation, Surgical↗

[Propane-induced tissue damage: burn or freezing injury?].

Tissue damage due to direct contact of liquid propane with the integument is extremely rare. Only five such cases have been described in the literature. We report the case of a girl who sustained a full-thickness skin necrosis of 14.5 % of her body surface area. There is little agreement about the optimal treatment of these injuries in previous reports. The pathophysiological mechanism suggests a freezing injury. The treatment, however, should be analogous to that of third-degree burns.

Adolescent↗