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Papers by B. Klosterhalfen

Research paper thumbnail of Induction of heat shock protein 70 (HSP70) by zinc bis (dl-hydrogen aspartate) reduces ischemic small-bowel tissue damage in rats

Langenbecks Archiv für Chirurgie, 1997

The aim of the study was to determine whether the induction of HSP70 by Zn 2+ is able to protect ... more The aim of the study was to determine whether the induction of HSP70 by Zn 2+ is able to protect the small bowel of rats against ischemia. Twenty-four male Wistar rats (weight 200-300 g) were divided into four groups:

Research paper thumbnail of Septischer Schock und multiples Organversagen in der chirurgischen Intensivmedizin

Langenbecks Archiv fur Chirurgie, 1993

Research paper thumbnail of Impact of Polymer Pore Size on the Interface Scar Formation in a Rat Model

Journal of Surgical Research, 2002

The surgical therapy of hernias is increasingly based on reinforcement with alloplastic material,... more The surgical therapy of hernias is increasingly based on reinforcement with alloplastic material, in particular surgical meshes. The biological response to these foreign bodies largely depends on the selected material and its structure. In comparison to the physiological scar process following a simple abdominal wall incision, the chronic inflammation at the interface to the polymers lead to specific morphological alterations. In the present study two meshes with different pore sizes were implanted into rats: a heavy-weight and small-pore-sized mesh (hw-mesh) made of nonabsorbable polypropylene monofilaments and a low-weight large-pore-sized mesh consisting of polypropylene and of absorbable polyglactin multifilaments (lw-mesh). A suture repair of a laparotomy served as control. After 7, 14, 21, and 90 days the mesh area was analyzed with regard to tissue and cellular response. Over the whole observation period morphometric analysis indicated an improved integration of the lw-mesh with reduction of both inflammation and fibrosis, whereas the hw-mesh induced an intense chronic inflammation concomitant with an intensified bridging scar reaction. On the cellular level these findings correspond to an elevated cell turnover, characterized by increased rates of apoptotic and proliferating cells. In contrast, the tissue reaction to the lw-mesh achieved levels almost similar to those of the physiological scaring process in the control group. In conclusion, the present data confirm the development of a chronic inflammatory foreign body reaction at the interface to both hw-meshes and lw-meshes; however, the use of lw-meshes showed superior tissue integration. With regard to the quite similar polymer surface the pore size appears to be of major importance in tissue reaction and for the biocompatibility of mesh structures.

Research paper thumbnail of Evidence for macrophage-mediated defluorization of a Teflon vascular graft

Journal of Materials Science: Materials in Medicine, 1996

Research paper thumbnail of Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface, the bacteria adherence, and thein vivo consequences in a rat model

Journal of Biomedical Materials Research, 2002

Within the last decade hernia surgery has changed from suture repair to mesh repair. Biomaterials... more Within the last decade hernia surgery has changed from suture repair to mesh repair. Biomaterials, and multifilaments in particular, are thought to increase the risk of infection. Therefore, the aim of this study was to study the influence of the presence of either a monofilament or a multifilament mesh material on the bacterial infection risk. The filament surface of a monofilament and a multifilament mesh were calculated on the basis of a theoretical model. The adherence of Staphylococcus aureus was measured in vitro by fluorescence analysis. Additionally, the two mesh materials (8-mm platelets) were implanted subcutaneously in Sprague-Dawley rats with daily surveillance for clinical signs of infection. After 7 days the meshes were explanted for histological and microbiological analysis. Calculations of the mesh surface area revealed a higher level for the multifilament mesh. The extent of adherent bacteria corresponded to the estimated filament surface in vitro. In vivo, the implantation of meshes in the presence of 5 x 10(6) S. aureus did not show an increased infection rate in rats with either monofilament or multifilament material, compared to the control groups (mesh implantation without S. aureus contamination). However, after 7 days bacteria were still detectable in the majority of the implantation sites, and a clinically inapparent intensification of local inflammation and fibrosis was induced. The increased surface area of a multifilament meshes promotes the persistence of bacteria in the implant bed, though this alone is not sufficient to create a clinically apparent infection. This might explain the development of mesh-related infections after a delay of several months or even years. In vivo, the adherence of bacteria to the implant material depends on the surface area, which favors the use of monofilament materials.

Research paper thumbnail of Computed Tomography and Histologic Results in the Early Stages of Endotoxin-Injured Pig Lungs as a Model for Adult Respiratory Distress Syndrome

Investigative Radiology, 1993

To determine early radiographic changes in diffuse alveolar injury, the authors correlated comput... more To determine early radiographic changes in diffuse alveolar injury, the authors correlated computed tomography (CT) and histopathology in pigs with recurrent endotoxinemia. Five pigs received recurrent endotoxin over a 17-hour period. Three pigs received physiologic saline and served as controls. Hemodynamic and blood-gas data were analyzed. CT was performed immediately before killing the animals. The lungs were cut into 5-mm-thick slices in the same axis as the CT scans and were investigated by light and electron microscopy. Hemodynamic data, blood-gas analysis, and morphologic changes closely simulated the clinical situation of septic shock in the five pigs that had received endotoxin. Results of histologic examination depicted changes similar to those associated with adult respiratory distress syndrome (ARDS). CT clearly demonstrated both interstitial, and to a minor degree, intra-alveolar lesions in the endotoxin-injected group, which correlated well with dilated lymph vessels, thickened interstitium, and areas of dystelectasis on histologic examination. Although there was a rather uniform clinical picture, CT and histologic findings showed different degrees of involvement. CT clearly depicts changes in endotoxin-injured pig lungs in an early clinical state, which are similar to changes associated with ARDS on histologic examination.

Research paper thumbnail of Expression of the Extracellular Matrix Proteins Collagen I, Collagen III and Fibronectin and Matrix Metalloproteinase-1 and -13 in the Skin of Patients with Inguinal Hernia

European Surgical Research, 1999

Although abnormal collagen metabolism has been ascribed an important role in the high recurrence ... more Although abnormal collagen metabolism has been ascribed an important role in the high recurrence rates after surgical hernia repair, knowledge on tissue sampled in the region affected by inguinal hernias is poor. In the present study, we determined collagen type I and type III in the skin of adult patients with indirect and direct inguinal hernias by both immunohistochemistry and Western blot analysis. In addition, we quantified the immunohistochemical expression of fibronectin and matrix metalloproteinase (MMP)-1 and -13. The results indicated that the ratio of collagen type I/III was significantly decreased in the skin of patients with either indirect (n = 9) or direct hernia (n = 7), with a concomitant increase in collagen type III (p < 0.001 vs. controls, n = 7, without affection of the inguinal region). There was no significant difference between patients with indirect and direct hernia (p > 0.05). MMP-13 was not expressed in any of the skin samples investigated, whereas MMP-1 was found in the epidermis. Fibronectin was predominantly detected at the epidermal-dermal junction. MMP-1, MMP-13 and fibronectin levels were significantly different between patients and controls (p > 0. 05). We conclude that in contrast to the unchanged expression of fibronectin and MMP-1 and MMP-13, the decreased ratios of collagen tpye I/III with the basically increased amount of collagen type III could be of significant importance for the pathophysiology of hernias. The specific ratio collagen I/III probably reflects the altered structural integrity and mechanical stability of the connective tissue in both indirect and direct hernias. Moreover, our findings stress that hernias should be regarded as the manifestation of a systemic disease in the inguinal region with a genetic background, explaining the high recurrence rates after repeated suture repair, as well as the usefulness of surgical meshes in this clinical setting.

Research paper thumbnail of Caecal-diverticulitis: A rare differential diagnosis for right-sided lower abdominal pain

Colorectal Disease, 2003

Objective There are several differential diagnoses for acute abdominal discomfort with pain refer... more Objective There are several differential diagnoses for acute abdominal discomfort with pain referred to the right lower quadrant region. The objective of this report is to outline our experience with diverticulitis of the caecum, which is a rare condition that is particularly difficult to diagnose correctly pre-operatively.

Research paper thumbnail of Shrinking of polypropylene mesh in vivo: an experimental study in dogs

European Journal of Surgery, 2003

Objective: To assess the extent of shrinkage of meshes used for hernia repair. Design: Experiment... more Objective: To assess the extent of shrinkage of meshes used for hernia repair. Design: Experimental study in dogs. Setting: University hospital, Germany and University Research Centre, Moscow. Animals: 10 dogs had monofilament polypropylene meshes that weighed 95 g/m 2 (Marlex 1 ) or multifilament reduced polypropylene meshes combined with polyglactin 910 that weighed 55 g/m 2 (Soft Hernia Mesh 1 ) implanted for either 3 or 6 months. Main outcome measures: Histological appearance and radiological assessment of the position and area of the mesh. Results: After 4 weeks the area of mesh in the monofilament group was reduced from to 139 (11) to 75 (8) cm 2 (54%) and that of the multifilament from 116 to 77 (20) cm 2 (66%). The multifilament mesh with the reduced amount of polypropylene showed less inflammatory response and less shrinkage. The mesh did not seem to have moved. Conclusion: Meshes that contain a lot of polypropylene shrink to about 30%-50% of their original size after 4 weeks, requiring an overlap of at least 3 cm if implanted subfascially. Reduction in the polypropylene content decreases both the inflammatory response and the shrinkage. Meshes with big pores are less likely to fold and improve compatibility.

Research paper thumbnail of Influence of polyglactin-coating on functional and morphological parameters of polypropylene-mesh modifications for abdominal wall repair

Biomaterials, 1999

Regarding oversized mechanical properties of most of the currently available materials a new mesh... more Regarding oversized mechanical properties of most of the currently available materials a new mesh was developed (ETHICON, Norderstedt, Germany) and exactly adopted to the physiology of the human abdominal wall by reducing the amount of polypropylene (weight of <30 g/m2; mesh A). The consecutive increase of pores size as well as the use of multifilaments led to a pronounced increase of flexibility. To improve the handling during operation the initial stiffness of this low-weight large pores mesh was increased by strengthening with different amounts of absorbable polyglactin (combination of glycolide and lactide) in various forms: by coating (mesh B), adding multifilament polyglactin filaments (mesh C, Vypro) or both (mesh D), respectively. To test the consequences of the different supplementary techniques all mesh variants are implanted in a rat model. Over implantation intervals of 3, 7, 14, 21 and 90 days we measured the tensile strength, the resulting stiffness and surveyed the tissue response, particularly in regard to the extent of inflammation and to the induced fibrosis. The results proved a sufficient mechanical stability of the material reduced and pure polypropylene mesh A without restriction of the mobility of the abdominal wall compared with a group that had simple laparotomy and closure. The histological analysis of the interface showed a minor inflammatory reaction and a dense vascularisation. The addition of polyglactin multifilaments (mesh C) reduces the number of macrophages and granulocytes as indicators for acute inflammation, showing generally a scar formation limited merely to the perifilamentary region. The abdominal wall compliance remained unchanged compared with mesh A. The coating of the polypropylene with polyglactin (mesh B and D) appeared to change the tissue reaction remarkably, favouring the formation of a connective tissue capsule around the whole mesh. The mechanical testing revealed an apparent protrusion with an increase of curvature of the artificial abdominal wall at rising intraabdominal pressures. The entire coating of the polypropylene surface with polyglactin induces an all embedding scar plate, filling out the pores and forming a tissue capsule. The complex interaction of tissue and implanted biomaterials with their distinct alterations of the tissue response confirms the necessity of in vivo experiments even after 'minor' modifications. Whereas the addition of polyglactin filaments appears to be favourable, the coating of polypropylene with polyglactin seems to hinder the incorporation of the mesh.

Research paper thumbnail of 1772 What Can We Learn from Explanted Slings and Meshes in Pelvic Floor Surgery?

The Journal of Urology, 2010

Research paper thumbnail of Induction of heat shock protein 70 (HSP70) by zinc bis (dl-hydrogen aspartate) reduces ischemic small-bowel tissue damage in rats

Langenbecks Archiv für Chirurgie, 1997

The aim of the study was to determine whether the induction of HSP70 by Zn 2+ is able to protect ... more The aim of the study was to determine whether the induction of HSP70 by Zn 2+ is able to protect the small bowel of rats against ischemia. Twenty-four male Wistar rats (weight 200-300 g) were divided into four groups:

Research paper thumbnail of Septischer Schock und multiples Organversagen in der chirurgischen Intensivmedizin

Langenbecks Archiv fur Chirurgie, 1993

Research paper thumbnail of Impact of Polymer Pore Size on the Interface Scar Formation in a Rat Model

Journal of Surgical Research, 2002

The surgical therapy of hernias is increasingly based on reinforcement with alloplastic material,... more The surgical therapy of hernias is increasingly based on reinforcement with alloplastic material, in particular surgical meshes. The biological response to these foreign bodies largely depends on the selected material and its structure. In comparison to the physiological scar process following a simple abdominal wall incision, the chronic inflammation at the interface to the polymers lead to specific morphological alterations. In the present study two meshes with different pore sizes were implanted into rats: a heavy-weight and small-pore-sized mesh (hw-mesh) made of nonabsorbable polypropylene monofilaments and a low-weight large-pore-sized mesh consisting of polypropylene and of absorbable polyglactin multifilaments (lw-mesh). A suture repair of a laparotomy served as control. After 7, 14, 21, and 90 days the mesh area was analyzed with regard to tissue and cellular response. Over the whole observation period morphometric analysis indicated an improved integration of the lw-mesh with reduction of both inflammation and fibrosis, whereas the hw-mesh induced an intense chronic inflammation concomitant with an intensified bridging scar reaction. On the cellular level these findings correspond to an elevated cell turnover, characterized by increased rates of apoptotic and proliferating cells. In contrast, the tissue reaction to the lw-mesh achieved levels almost similar to those of the physiological scaring process in the control group. In conclusion, the present data confirm the development of a chronic inflammatory foreign body reaction at the interface to both hw-meshes and lw-meshes; however, the use of lw-meshes showed superior tissue integration. With regard to the quite similar polymer surface the pore size appears to be of major importance in tissue reaction and for the biocompatibility of mesh structures.

Research paper thumbnail of Evidence for macrophage-mediated defluorization of a Teflon vascular graft

Journal of Materials Science: Materials in Medicine, 1996

Research paper thumbnail of Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface, the bacteria adherence, and thein vivo consequences in a rat model

Journal of Biomedical Materials Research, 2002

Within the last decade hernia surgery has changed from suture repair to mesh repair. Biomaterials... more Within the last decade hernia surgery has changed from suture repair to mesh repair. Biomaterials, and multifilaments in particular, are thought to increase the risk of infection. Therefore, the aim of this study was to study the influence of the presence of either a monofilament or a multifilament mesh material on the bacterial infection risk. The filament surface of a monofilament and a multifilament mesh were calculated on the basis of a theoretical model. The adherence of Staphylococcus aureus was measured in vitro by fluorescence analysis. Additionally, the two mesh materials (8-mm platelets) were implanted subcutaneously in Sprague-Dawley rats with daily surveillance for clinical signs of infection. After 7 days the meshes were explanted for histological and microbiological analysis. Calculations of the mesh surface area revealed a higher level for the multifilament mesh. The extent of adherent bacteria corresponded to the estimated filament surface in vitro. In vivo, the implantation of meshes in the presence of 5 x 10(6) S. aureus did not show an increased infection rate in rats with either monofilament or multifilament material, compared to the control groups (mesh implantation without S. aureus contamination). However, after 7 days bacteria were still detectable in the majority of the implantation sites, and a clinically inapparent intensification of local inflammation and fibrosis was induced. The increased surface area of a multifilament meshes promotes the persistence of bacteria in the implant bed, though this alone is not sufficient to create a clinically apparent infection. This might explain the development of mesh-related infections after a delay of several months or even years. In vivo, the adherence of bacteria to the implant material depends on the surface area, which favors the use of monofilament materials.

Research paper thumbnail of Computed Tomography and Histologic Results in the Early Stages of Endotoxin-Injured Pig Lungs as a Model for Adult Respiratory Distress Syndrome

Investigative Radiology, 1993

To determine early radiographic changes in diffuse alveolar injury, the authors correlated comput... more To determine early radiographic changes in diffuse alveolar injury, the authors correlated computed tomography (CT) and histopathology in pigs with recurrent endotoxinemia. Five pigs received recurrent endotoxin over a 17-hour period. Three pigs received physiologic saline and served as controls. Hemodynamic and blood-gas data were analyzed. CT was performed immediately before killing the animals. The lungs were cut into 5-mm-thick slices in the same axis as the CT scans and were investigated by light and electron microscopy. Hemodynamic data, blood-gas analysis, and morphologic changes closely simulated the clinical situation of septic shock in the five pigs that had received endotoxin. Results of histologic examination depicted changes similar to those associated with adult respiratory distress syndrome (ARDS). CT clearly demonstrated both interstitial, and to a minor degree, intra-alveolar lesions in the endotoxin-injected group, which correlated well with dilated lymph vessels, thickened interstitium, and areas of dystelectasis on histologic examination. Although there was a rather uniform clinical picture, CT and histologic findings showed different degrees of involvement. CT clearly depicts changes in endotoxin-injured pig lungs in an early clinical state, which are similar to changes associated with ARDS on histologic examination.

Research paper thumbnail of Expression of the Extracellular Matrix Proteins Collagen I, Collagen III and Fibronectin and Matrix Metalloproteinase-1 and -13 in the Skin of Patients with Inguinal Hernia

European Surgical Research, 1999

Although abnormal collagen metabolism has been ascribed an important role in the high recurrence ... more Although abnormal collagen metabolism has been ascribed an important role in the high recurrence rates after surgical hernia repair, knowledge on tissue sampled in the region affected by inguinal hernias is poor. In the present study, we determined collagen type I and type III in the skin of adult patients with indirect and direct inguinal hernias by both immunohistochemistry and Western blot analysis. In addition, we quantified the immunohistochemical expression of fibronectin and matrix metalloproteinase (MMP)-1 and -13. The results indicated that the ratio of collagen type I/III was significantly decreased in the skin of patients with either indirect (n = 9) or direct hernia (n = 7), with a concomitant increase in collagen type III (p < 0.001 vs. controls, n = 7, without affection of the inguinal region). There was no significant difference between patients with indirect and direct hernia (p > 0.05). MMP-13 was not expressed in any of the skin samples investigated, whereas MMP-1 was found in the epidermis. Fibronectin was predominantly detected at the epidermal-dermal junction. MMP-1, MMP-13 and fibronectin levels were significantly different between patients and controls (p > 0. 05). We conclude that in contrast to the unchanged expression of fibronectin and MMP-1 and MMP-13, the decreased ratios of collagen tpye I/III with the basically increased amount of collagen type III could be of significant importance for the pathophysiology of hernias. The specific ratio collagen I/III probably reflects the altered structural integrity and mechanical stability of the connective tissue in both indirect and direct hernias. Moreover, our findings stress that hernias should be regarded as the manifestation of a systemic disease in the inguinal region with a genetic background, explaining the high recurrence rates after repeated suture repair, as well as the usefulness of surgical meshes in this clinical setting.

Research paper thumbnail of Caecal-diverticulitis: A rare differential diagnosis for right-sided lower abdominal pain

Colorectal Disease, 2003

Objective There are several differential diagnoses for acute abdominal discomfort with pain refer... more Objective There are several differential diagnoses for acute abdominal discomfort with pain referred to the right lower quadrant region. The objective of this report is to outline our experience with diverticulitis of the caecum, which is a rare condition that is particularly difficult to diagnose correctly pre-operatively.

Research paper thumbnail of Shrinking of polypropylene mesh in vivo: an experimental study in dogs

European Journal of Surgery, 2003

Objective: To assess the extent of shrinkage of meshes used for hernia repair. Design: Experiment... more Objective: To assess the extent of shrinkage of meshes used for hernia repair. Design: Experimental study in dogs. Setting: University hospital, Germany and University Research Centre, Moscow. Animals: 10 dogs had monofilament polypropylene meshes that weighed 95 g/m 2 (Marlex 1 ) or multifilament reduced polypropylene meshes combined with polyglactin 910 that weighed 55 g/m 2 (Soft Hernia Mesh 1 ) implanted for either 3 or 6 months. Main outcome measures: Histological appearance and radiological assessment of the position and area of the mesh. Results: After 4 weeks the area of mesh in the monofilament group was reduced from to 139 (11) to 75 (8) cm 2 (54%) and that of the multifilament from 116 to 77 (20) cm 2 (66%). The multifilament mesh with the reduced amount of polypropylene showed less inflammatory response and less shrinkage. The mesh did not seem to have moved. Conclusion: Meshes that contain a lot of polypropylene shrink to about 30%-50% of their original size after 4 weeks, requiring an overlap of at least 3 cm if implanted subfascially. Reduction in the polypropylene content decreases both the inflammatory response and the shrinkage. Meshes with big pores are less likely to fold and improve compatibility.

Research paper thumbnail of Influence of polyglactin-coating on functional and morphological parameters of polypropylene-mesh modifications for abdominal wall repair

Biomaterials, 1999

Regarding oversized mechanical properties of most of the currently available materials a new mesh... more Regarding oversized mechanical properties of most of the currently available materials a new mesh was developed (ETHICON, Norderstedt, Germany) and exactly adopted to the physiology of the human abdominal wall by reducing the amount of polypropylene (weight of <30 g/m2; mesh A). The consecutive increase of pores size as well as the use of multifilaments led to a pronounced increase of flexibility. To improve the handling during operation the initial stiffness of this low-weight large pores mesh was increased by strengthening with different amounts of absorbable polyglactin (combination of glycolide and lactide) in various forms: by coating (mesh B), adding multifilament polyglactin filaments (mesh C, Vypro) or both (mesh D), respectively. To test the consequences of the different supplementary techniques all mesh variants are implanted in a rat model. Over implantation intervals of 3, 7, 14, 21 and 90 days we measured the tensile strength, the resulting stiffness and surveyed the tissue response, particularly in regard to the extent of inflammation and to the induced fibrosis. The results proved a sufficient mechanical stability of the material reduced and pure polypropylene mesh A without restriction of the mobility of the abdominal wall compared with a group that had simple laparotomy and closure. The histological analysis of the interface showed a minor inflammatory reaction and a dense vascularisation. The addition of polyglactin multifilaments (mesh C) reduces the number of macrophages and granulocytes as indicators for acute inflammation, showing generally a scar formation limited merely to the perifilamentary region. The abdominal wall compliance remained unchanged compared with mesh A. The coating of the polypropylene with polyglactin (mesh B and D) appeared to change the tissue reaction remarkably, favouring the formation of a connective tissue capsule around the whole mesh. The mechanical testing revealed an apparent protrusion with an increase of curvature of the artificial abdominal wall at rising intraabdominal pressures. The entire coating of the polypropylene surface with polyglactin induces an all embedding scar plate, filling out the pores and forming a tissue capsule. The complex interaction of tissue and implanted biomaterials with their distinct alterations of the tissue response confirms the necessity of in vivo experiments even after 'minor' modifications. Whereas the addition of polyglactin filaments appears to be favourable, the coating of polypropylene with polyglactin seems to hinder the incorporation of the mesh.

Research paper thumbnail of 1772 What Can We Learn from Explanted Slings and Meshes in Pelvic Floor Surgery?

The Journal of Urology, 2010