Publications (20)48.84 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Syndromes with focal overgrowth are sporadic diseases and comprise Proteus syndrome and congenital lipomatous overgrowth, vascular malformations, and epidermal naevi (CLOVE) syndrome, and isolated hemihyperplasia. We describe 3 children classified according to standard criteria with dysregulated growth of various tissues that was excised, together with excess toes, and tumours. Correct classification facilitates diagnosis and operations. Interdisciplinary treatment and follow-up are recommended to prevent disfiguration.
- [Show abstract] [Hide abstract] ABSTRACT: The ability to regulate wound contraction is critical for wound healing as well as for pathological contractures. Matrix metalloproteinases (MMPs) have been demonstrated to be obligatory for normal wound healing. This study examined the effect that the broad-spectrum MMP inhibitor BB-94 has when applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound closure through a twofold mechanism; by blocking keratinocyte migration and thereby blocking the necessary keratinocyte-fibroblast interactions needed for myofibroblast formation and by inhibiting the activation of latent TGF-beta1.
- [Show abstract] [Hide abstract] ABSTRACT: The preoperative diagnostic imaging of peripheral nerve lesions and the postoperative monitoring of microsurgically coapted nerves remain unsolved problems. The aim of this study was to investigate peripheral nerve regeneration after complete neurotmesis with magnetic resonance imaging techniques. Study groups included 70 rats. Their right sciatic nerve was either cut and left untreated or epineurially coapted. After postoperative days 3, 6, 10, and 14 and then weekly until postoperative day 84, these rats underwent scanning at 4.7 T. T2 signal intensities of the nerves were analyzed. In parallel, on postoperative days 3, 6, 10, 14, 21, 28, 42, 63, or 84, rats were killed for histologic processing. These findings were related to the corresponding images. After an initial T2 signal increase of the nerves in both groups, the coapted group demonstrated a major T2 signal decrease in the distal part of the nerve after postoperative day 21, whereas in the unrepaired group a signal decrease was not observed until postoperative day 42. Differences between the two groups were significant at postoperative days 3, 6, and 28 and thereafter. The signal decrease in the coapted nerves could be correlated to the ingrowth of regenerating axons observed by histology. Moreover, the continuity of coapted nerves or an explicit gap in the unrepaired group was detectable at every time point. This study presents novel magnetic resonance imaging data regarding regeneration after neurotmesis. High-field-strength magnetic resonance imaging has the potential to diagnose a discontinuity within a nerve of interest and monitor its regeneration after coaptation.
- [Show abstract] [Hide abstract] ABSTRACT: Vaginal reconstruction has been performed for more than a century. Main complications are vaginal stenosis requiring dilatation, dyspareunia, excessive mucus secretion, and poor aesthetic and functional outcome. Here we report a new operation method modified after Baldwin for intestinal vaginoplasty in a patient with pelvic exenteration after spinal cell carcinoma of the vagina. Because of balanced liquid resorption and mucus secretion with sufficient vessel length in the terminal ileum, this intestinal segment was chosen. A J-pouch of distal ileum was constructed pedicled on the ileocolic artery and accompanying nervous plexus, transferred into the lower pelvis and sutured to the vaginal stump. One year follow-up showed a highly satisfied, sexually active patient, with adequate vaginal size, optimal lubrication and no molesting fecal odor. Terminal ileum J-pouch vaginoplasty is an optimal method for vaginal reconstruction providing a sufficient vaginal lumen and lubrication and thereby restoring patients' sexual life and increasing life quality.
- [Show abstract] [Hide abstract] ABSTRACT: A 43-year-old healthy man presented with bilateral hypertrophy of the first dorsal interosseus muscles of both hands. Neurophysiologic and laboratory examinations revealed no pathologic findings. Doubled muscle width was found by ultrasound. Myopathic changes were present in muscle biopsy with varying fiber sizes but without inflammatory features. The clinical impression of massive bilateral symmetric enlargement of the first dorsal interosseus muscles was characterized by subtle, non-specific muscular pathology.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to evaluate the feasibility, quality, and possible future implications of magnetic resonance imaging (MRI) of the human hand and wrist at 7 T. Images of the left hand of a healthy volunteer were acquired with a 7- and a 1.5-T whole body system and comparatively analyzed. Axial and coronal two-dimensional gradient echo (GRE) images with inflow saturation, coronal 3D GRE images, and time-of-flight angiographies were obtained without averaging. Image details were related to the complex hand anatomy. With the 7-T protocols established in this study, high-quality and high-resolution images of the hand and wrist were obtained. In the 2D GRE images at 7 T, small anatomical structures of the hand were depicted in vivo with superior detail and resolution, compared to 1.5 T and published studies at lower field strength. Signal-to-noise ratios (SNRs) were approximately five times higher at 7 T compared to 1.5 T. Additionally, thin 3D GRE images with good quality of the whole hand were obtained in a short acquisition time. Moreover, time-of-flight angiographies of the small hand arteries have been acquired without the application of contrast agents. Seven-tesla imaging of the hand can be used in vivo with ultra-high resolution and sufficient SNR. It allows for exact delineation of most anatomical structures including nerves, muscles, tendons, ligaments, cartilage, and blood vessels.
- [Show abstract] [Hide abstract] ABSTRACT: The rectus femoris muscle flap is well known for its reliable anatomy, the ease with which it can be harvested, and its great versatility. As a pedicled or free flap, it is used to cover soft-tissue defects and to recreate motor function. Although the muscle is very reliable, it is not well respected because of its assumed donor-site morbidity, such as weakened knee extension force and decreased range of motion of the knee. To date, these clinical assumptions have only rarely been quantified in terms of objective scores, concerning force deficit and functional or aesthetic outcome. From 1995 to 2002, the authors treated 24 patients with pedicled rectus femoris muscle flaps. Fourteen patients were followed up. Follow-up time ranged from 3 to 56 months postoperatively. The results were evaluated by a standard questionnaire in which pain in relation to walking distance, subjective feeling of weakness, sensibility disorders, everyday function, and aesthetic aspects were assessed. Range of motion in the hip and the knee was measured. For objective verification of a decrease of maximal voluntary contraction force of the remaining quadriceps muscle and for detecting differences in true muscular capacity and voluntary activation, 10 patients with unilateral rectus femoris flaps were tested using the twitch interpolation technique. The authors' patients assessed the remaining function and the aesthetic result of the thigh as at least satisfactory. Two patients complained about pain and weakness in the thigh. Eight patients reported hypesthesia in the lateral suprapatellar region. The maximal voluntary contraction and true muscular capacity values were reduced by 21.8 percent and 18 percent, respectively, when compared with the healthy leg. The range of motion in the knee and hip was not influenced by muscle harvesting. The twitch interpolation technique revealed a mild voluntary activation deficit, probably caused by inhibitory regulation in the spinal cord. In conclusion, donor-site morbidity of the rectus femoris muscle flap is evident but well compensated. There is no decrease in active range of motion in the knee and hip. Patient satisfaction with the functional and aesthetic outcome was high.
- [Show abstract] [Hide abstract] ABSTRACT: A nerve gap must be bridged by autologous nerve grafts that serve as scaffold and consist of viable Schwann cells that promote regeneration. Owing to the necessary immunosuppression, nerve allografts remain limited to special cases. Alternatively, tissue engineering of peripheral nerves focuses on the implantation of cultured Schwann cells into suitable scaffolds. We established grafts from Schwann cells and basal lamina from acellular muscles. These grafts offer a regeneration that is comparable to autologous nerve grafts. Using a rat model (DALEW.1W strain), the present study evaluates the host response to acellular muscle allografts by assessing cellular reaction major histocompatability (MHC) class I and II, lymphocytes, macrophages. The results were compared to untreated muscle allografts. Macroscopically, the untreated muscles showed a strong inflammatory reaction as a sign of rejection, whereas the acellular muscle offered only minor reactions in the periphery of the graft. Expression of MHC I and II and invasion of CD4/CD8 positive cells and macrophages was pronounced after grafting the untreated muscles. Only a moderate reaction was noted for these parameters after acellular grafting. The acellular muscle graft is not completely free of cellular response; however the reaction is considered to be moderate and is located only in the periphery. To date, synthetic scaffolds that represent endoneurial tube-like structures and allow sufficient adhesion of Schwann cells and axonal regeneration are not available. The decreased response to acellular muscle allografts offers at least a basis for further experiments.
- [Show abstract] [Hide abstract] ABSTRACT: To overcome the problems of limited donor nerves for nerve reconstruction, we established nerve grafts made from cultured Schwann cells and basal lamina from acellular muscle and used them to bridge a 2-cm defect of the rat sciatic nerve. Due to their basal lamina and to viable Schwann cells, these grafts allow regeneration that is comparable to autologous nerve grafts. In order to enhance regeneration, insulin-like growth factor (IGF-I) was locally applied via osmotic pumps. Autologous nerve grafts with and without IGF-I served as controls. Muscle weight ratio was significantly increased in the autograft group treated with IGF-I compared to the group with no treatment; no effect was evident in the tissue-engineered grafts. Autografts with IGF-I application revealed a significantly increased axon count and an improved g-ratio as indicator for "maturity" of axons compared to autografts without IGF-I. IGF-I application to the engineered grafts resulted in a decreased axon count compared to grafts without IGF-I. The g-ratio, however, revealed no significant difference between the groups. Local administration of IGF-I improves axonal regeneration in regular nerve grafts, but not in tissue-engineered grafts. Seemingly, in these grafts the interactive feedback mechanisms of neuron, glial cell, and extracellular matrix are not established, and IGF-I cannot exert its action as a pleiotrophic signal.
- [Show abstract] [Hide abstract] ABSTRACT: The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts.
- [Show abstract] [Hide abstract] ABSTRACT: Clenbuterol is known to act as a neuroprotective substance in the central nervous system, and also reduces muscle atrophy after denervation. The aim of this study was to evaluate its influence on peripheral nerve regeneration. The rat sciatic nerve model was used in four groups (n = 8 per group). After complete nerve transection and microsurgical coaptation, two groups received a daily oral dose of 100 microg/kg clenbuterol and two served as controls. Regeneration was assessed clinically, histologically, and morphometrically after 4 and 6 weeks. The weight ratios of calf muscles were calculated. Histological examination showed significantly increased axon counts in the clenbuterol group and a better degree of myelination. Muscle weight ratios of the clenbuterol group were significantly increased after 6 weeks, and the animals showed improved function of the hindlimb. Thus, therapy with 100 microg/kg clenbuterol daily after coaptation of a sciatic nerve showed a positive influence on clinical, histological, and morphometrical parameters in the rat model. The underlying mechanism remains unclear.
- [Show abstract] [Hide abstract] ABSTRACT: Bioengineering is considered to be the laboratory-based alternative to human autografts and allografts. It ought to provide "custom-made organs" cultured from patient's material. Venous grafts and acellular muscle grafts support axonal regeneration only to a certain extent because of the lack of viable Schwann cells in the graft. We created a biologic nerve graft in the rat sciatic nerve model by implanting cultured Schwann cells into veins and acellular gracilis muscles, respectively. Autologous nerve grafts and veins and acellular muscle grafts without Schwann cells served as controls. After 6 and 12 weeks, regeneration was assessed clinically, histologically, and morphometrically. The polymerase chain reaction analvsis showed that the implanted Schwann cells remained within all the grafts. The best regeneration was seen in the control; after 12 weeks the number of axons was increased significantly compared with the other grafts. A good regeneration was noted in the muscle-Schwann cell group, whereas regeneration in both of the venous grafts and the muscle grafts without Schwann cells was impaired. The muscle-Schwann cell graft showed a systematic and organized regeneration including a proper orientation of regenerated fibers. The venous grafts with Schwann cells showed less fibrous tissue and disorganization than the veins without Schwann cells, but failed to show an excellent regeneration. This might be attributed to the lack of endoneural-tube-like components serving as scaffold for the sprouting axon. Although the conventional nerve graft remains the gold standard, the implantation of Schwann cells into an acellular muscle provides a biologic graft with basal lamina tubes as pathways for regenerating axons and the positive effects of Schwann cells producing neurotrophic and neurotropic factors, and thus, supporting axonal regeneration.
Article: Neuroma[Show abstract] [Hide abstract] ABSTRACT: Schwann cells are used in combination with biological matrices as tissue engineered nerve grafts in animal models offering a new therapeutic approach for treatment of lesions of the peripheral nervous system. A high yield of human Schwann cells from adult donors is only achieved by pharmacological stimulation, which should, however, be avoided in clinical therapy. Here, we establish cultures of activated human Schwann cells which were isolated from peripheral nerve neuroma which developed after a median nerve lesion. To allow nerve reconstruction neuroma have to be resected. Such neuroma tissue is virtually predegenerated and shows activation of Schwann cells, implying good adherence and high mitotic activity. This allows, irrespective of donor age, growing within a short time period and without any pharmacological treatment.
- [Show abstract] [Hide abstract] ABSTRACT: The utilization of viable biological nerve graft substitutes and nerve allografts raises the problem of nerve storage. To clarify this, rat sciatic nerve segments were harvested and stored in Dulbecco's modified eagle medium. The segments were divided into three groups. In the first group, no cryoprotectant was added, whereas the second had 10% dimethyl sulfoxide (DMSO) added as cryoprotectant. These two groups of nerve segments were subjected to controlled freezing. In a third group, segments were frozen uncontrolled in liquid nitrogen (-196 degrees C). All nerves were replanted orthotopically. Fresh conventional autografts (fourth group) served as control group. Histologically, freezing did not affect the structural elements such as basal lamina tubes and perineurial tissue. Morphometrically, all cryopreserved grafts had significantly reduced axon counts and less myelinization than did controls. Cryoprotected nerves (group 2) showed no different morphometric parameters compared with the group without DMSO (group 1). Controlled freezing was superior to uncontrolled freezing (group 3). Impaired regeneration was attributed mainly to delayed Wallerian degeneration and slower revascularization. Moreover, decreased survival of resident Schwann cells in the graft may impair regeneration due to the lack of neurotrophic, neurotropic, and attachment factors in early regeneration. Grafts subjected to controlled freezing support axonal regeneration to a certain extent, but further studies are required to assess various cooling patterns, cryoprotectants, and graft revascularization.
- [Show abstract] [Hide abstract] ABSTRACT: PURPOSE: Nerve allografts are highly antigenic and, thus, require the continuous use of immunosuppressive drugs. FK 506 was found to pre-vent rejection successfully. However, clinically neurotoxic complications have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been shown after nerve crush experiments. To investigate whether a possible regeneration pro-moting potency of FK 506 is determined via an influence on Schwann cells, Schwann cells were cultured from the sciatic nerve of the rat. METHODS: The effect of 100 micro M FK 506 administered daily on these cultures was assessed microscopically over a period of seven days and compared to an untreated control group of cultures. Additionally, the changes in intracellular calcium were recorded using a laser scanning microscope. In vivo regeneration of autologous rat sciatic nerve grafts was assessed clinically, histologically and morphometrically after two and six weeks. The animals received a daily administration of 0.6 mg FK 506/kg body weight, the control received saline. RESULTS: In vitro FK 506 increased the Schwann cell number in culture significantly compared to non treated cultures, while the fibrocyte population was decreased. FK 506 caused a transient increase of intracellular calcium levels in cultured cells. In vivo, a significantly higher axon count was observed in the FK 506 treated grafts after two weeks regeneration compared with controls. Good regeneration was noted in all grafts after six weeks regeneration. CONCLUSIONS: The increased axon counts and decreased myelin debris in the FK 506 grafts after two weeks indicate an accelerated Wallerian degeneration and increased axon sprouting into the graft initially. The inhibition of calcineurin activity is not the mediator of the neurotrophic effect. FK 506 promotes axonal regeneration through binding to FKBP-12. The increase of intracellular calcium may induce Schwann cell pro-liferation via calmodulin. The therapeutic relevance for autologous nerve grafting, however, has to be defined in further studies.
- [Show abstract] [Hide abstract] ABSTRACT: Denatured or acellular muscle grafts are known to support axonal regeneration. With increasing gap length, failure of regeneration is evident, due to the lack of viable Schwann cells in the graft. The authors created a biologic nerve conduit, in a rat sciatic nerve model, by implanting cultured Schwann cells into an acellular gracilis muscle. Autologous nerve grafts and acellular muscle grafts without Schwann cells served as controls. After 6 weeks, regeneration was assessed clinically, histologically, and morphometrically. Polymerase chain reaction (PCR) analysis showed that the implanted Schwann cells remained viable within the graft. Good regeneration was noted in the muscle-Schwann cell group, while regeneration in the muscle grafts without Schwann cells was significantly impaired. The muscle-Schwann cell graft demonstrated systematic and organized regeneration, including the proper orientation of regenerated fibers. The number of axons regenerating through the muscle-Schwann cell grafts was significantly increased, compared with the acellular muscle without Schwann cells. Implantation of Schwann cells into acellular muscle thus provided a biologic conduit with large basal lamina tubes, as a pathway for regenerating axons. The positive effects of Schwann cells, producing neurotrophic and neurotropic factors, supported axonal regeneration.
- [Show abstract] [Hide abstract] ABSTRACT: In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.
- [Show abstract] [Hide abstract] ABSTRACT: Acellular muscle grafts can support axonal regeneration over short gaps. Due to the lack of viable Schwann cells in the grafts, failure of regeneration is evident with increasing gap lengths. To create a biological nerve conduit, Schwann cells were implanted into acellular muscle. The grafts were then incubated in vitro and assessed histologically and morphometrically. For cultivation of the Schwann cells, rat sciatic nerves were allowed to predegenerate to obtain a high cell yield. Rat gracilis muscles were harvested and made acellular by a liquid nitrogen treatment. After Schwann cell implantation, the muscles were incubated in vitro for 2, 5, and 7 days. S100-immunostaining, NGF, and N-cadherin, characterized the Schwann cells within the muscle. Viability was assessed by fluoresceine-fluorescence staining. Proliferation was determined by BrdU-DNA incorporation. Cell implantation did not to affect Schwann cell viability. Cells were seen throughout the entire length of the muscle basal lamina. They aligned and formed a cell column. Immunostained for S-100, implanted cells showed 100 percent staining. N-cadherin and NGF were expressed by all of the S-100 positive cells. Predegeneration is considered to be a highly efficacious method, if a high yield of activated Schwann cells is required. The successful implantation of the cells into an acellular muscle provides the possibility of a biologic conduit, offering the advantage of large basal lamina tubes serving as a pathway for regenerating axons. It also provides the beneficial effects of viable Schwann cells that produce neurotrophic and neurotropic factors to support axonal regeneration. Functional outcomes require evaluation in further in vivo studies.
Magdeburg, Saxony-Anhalt, Germany
- Clinic for Plastic Surgery, Aesthetic and Hand Surgery