Biomedical subjects

B Klosterhalfen

Publications and source records attributed to B Klosterhalfen.

At least 91 records · Page 5Linked to original sources

PubMed1996

Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia.

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

[Progressive pneumoperitoneum in treatment of inguinal and scar hernias. Results of animal experiments and clinical applications].

Preoperative progressive pneumoperitoneum is a well-known, but sporadically used procedure in preparing patients with giant inguinal or incisional hernias for the operation. The technique requires frequent insufflation of air into the abdominal cavity in order to create space to accommodate herniated viscera and facilitate fascial repair with minimal tension. This article demonstrates the histological findings, technique, complications, advantages and long-term results of the preoperative progressive pneumoperitoneum in hernia repair.

Abdominal Muscles↗

PubMed1996

[Changes in abdominal wall mechanics after mesh implantation. Experimental changes in mesh stability].

The use of biomaterials for incisional hernia markedly reduces the recurrence rates. Disadvantages are high rates of local wound complications and restriction of mobility by the rigid "shell". The abdominal wall mobility after mesh implantation is analysed for eight different mesh materials. The initial textile testing reveals relevant differences in structure with marked asymmetry in the different directions. The materials are implanted as inlay in rats for 3, 7, 14, 21 and 90 days. The deformation of the abdominal wall following intraabdominal pressure of 0-70 mmHg (0-9.81 kPa) is documented by 3D-photogrammetry, the tensile strength by tearing of excised strips of mesh. Three commercial available materials and two laboratory modifications lead independently of their textile characteristics to a marked restriction of the rounded configuration of the abdominal wall. The tensile strength exceeds by far the physiologically necessary value of 16 N/cm. Three newly developed meshes made of multifilament polypropylene with reduced amounts of material (21% and 28% relative to Marlex) lead to no restriction of the abdominal wall configuration yet have uncompromised stability. It might be possible to reduce the rate of local wound complications by the use of these newly developed meshes.

Abdominal Muscles↗

PubMed1996

Tumour-cell-endothelial interactions: free radicals are mediators of melanoma-induced endothelial cell damage.

Damage to vascular endothelium may play an important role during metastasis. We used a three-dimensional model of tumour cell extravasation to test the hypothesis that certain types of tumour cells are able to induce vascular endothelial cell injury. Multicellular tumour spheroids (MCTS) of 14 human cancer cell lines and spheroids from two benign cell lines were transferred onto confluent monolayers of human endothelial cells (EC). MCTS from 4 of 7 melanoma cell lines induced damage of the endothelium which was closely associated with tumour cell attachment. Endothelial cell injury became evident morphologically by loss of cell membrane integrity and sensitivity to shear stress. Similar results were obtained with EC derived from human umbilical veins, umbilical arteries and saphenous veins. Addition of the oxygen radical scavenger catalase showed a dose- and time-dependent inhibition (up to 48 h) of EC damage in the case of the melanoma cell lines ST-ML-11, ST-ML-14 and SK-MEL-28. The scavenging enzyme superoxide dismutase proved to be protective (up to 12 h) in ST-ML-12 MCTS. In contrast, allopurinol, deferoxamine mesylate, ibuprofen, nor-dihydroguaretic acid, soybean trypsin inhibitor or aprotinin had no protective effect. None of the non-melanoma cancer cell lines or benign cells induced endothelial cell damage. Endothelial injury has been shown to enhance the process of metastasis. Our results suggest that free-radical-mediated endothelial cell damage may be one of the mechanisms contributing to the devastating metastatic potential of melanoma.

Catalase↗

PubMed1996

The role of the microcirculation in multiple organ dysfunction syndrome (MODS): a review and perspective.

Major advances in intensive care medicine during the past two decades have altered the spectrum of disease encountered by intensive care physicians, anaesthesiologists, traumatologists and pathologists. One of the most important manifestations of severe trauma or infections is the multiple organ dysfunction syndrome (MODS), a life-threatening condition that often ends in multiple organ failure (MOF) and death. Evidence gathered from clinical and morphological observations in humans, taken together with experimental animal studies and a vast accumulation of in vitro data, clearly indicate that the microcirculation lies at the centre of this complex process, which results in peripheral vascular insufficiency, inadequate oxygen delivery to vital organs, and hence, severe organ dysfunction. The multifunctional nature of the endothelium makes it a prime candidate for study of the pathomechanisms of MODS. This paper reviews the evidence for the hypothesis that the microcirculation, and in particular its endothelial component, has a central role in the pathogenesis of MODS. The evidence is reviewed principally from the standpoints of classical morbid anatomy and cell pathobiology.

Animals↗

PubMed1996

Macrophage reactions in septic arthritis.

With the aid of monoclonal antibodies, macrophages can be split into functionally distinct subpopulations on the basis of their phenotype. Absence of macrophage subtypes has been noted in chronic inflammatory processes, e.g. posttraumatic osteomyelitis, rheumatoid arthritis and sarcoidosis. In the inflammatory focus of acute septic arthritis (n = 13 patients) however, macrophages constitute the majority of immunocompetent cells. The inflammatory macrophage subtype 27E10 was clearly present in increased numbers in 11 of 13 biopsies from the inflammatory foci, showing the effector task of this subtype in synovial resistance. The anti-inflammatory macrophage subset RM3/1 was present in increased numbers in biopsies of infected tissue and the surrounding soft tissue. The occurrence of 25F9-positive macrophages, typical of the late phase of inflammation, varied widely in the biopsies.

Adolescent↗

PubMed1996

Local and systemic inflammatory mediator release in patients with acute and chronic posttraumatic osteomyelitis.

The local and systemic release of thromboxane A2, prostaglandin I2, leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were studied before and after operation in 29 patients with acute and 22 with chronic posttraumatic osteomyelitis. Twenty patients without osteomyelitis, who underwent operations for fractures of the lower extremities, served as controls. Blood and tissue samples from the osteomyelitic and control groups were collected under defined conditions and mediators were determined by radioimmunoassay (thromboxane B2, 6-keto-prostaglandin F1 alpha, LTB4) or by enzyme-linked immunosorbent assay (TNF-alpha, IL-1 beta, and IL-8). In addition, common parameters (leukocyte count, C-reactive protein, temperature) were measured. The best correlation with acute disease activity was given by TNF-alpha, IL-6, IL-8, and LTB4. Plasma levels of these mediators in acute osteomyelitis were significantly increased compared to chronic osteomyelitis and to controls, respectively. Tissue samples from osteomyelitic focus showed significantly increased levels for IL-8, IL-6, TNF-alpha, IL-1 beta, and LTB4 in acute osteomyelitis, whereas the values for TxB2 and 6-keto-prostaglandin F1 alpha were only slightly increased compared to the chronic osteomyelitis group. This study describes the local and systemic liberation of various mediators in acute and chronic posttraumatic osteomyelitis in detail for the first time and provides data for pre- and postoperative monitoring of disease activity and demonstrates new pathogenetic and therapeutic aspects of bone modulation in osteomyelitis.

Acute Disease↗

PubMed1996

[Monitoring critically ill intensive care patients by semi-invasive COLD (Cardiac-Output-Liver-Diseases) monitoring instead of pulmonary artery catheterization].

The routine application of an arterial thermal-dye-dilution technique (so called COLD-Monitoring) offers new perspectives in the hemodynamic management of critically ill patients using a small invasive technique. COLD-Monitoring employs a computerized analysis of a double-indicator (temperature and dye) dilution technique which requires only a central venous catheter and a special fibre optic catheter with a temperature probe applied to the femoral artery. Especially in critically ill patients with septic course or multiple organ failure (MOF) COLD-monitoring serves to exactly measure volume and therefore distribution, to objectify capillary leakage by extravascular lung water index, to check the excretoric liver-function by plasma-deviation-rate of ICG and to perform a well controlled epinephrine therapy by measuring cardiac function index and systemic vascular resistance index.

Cardiac Catheterization↗

PubMed1995

Integrin expression on colorectal tumor cells growing as monolayers, as multicellular tumor spheroids, or in nude mice.

In this study we compared the expression of integrin alpha chains 2, 3, 4, 5, 6, v and the beta chains 1, 3, 4 in 2 colorectal carcinoma cell lines (HRT-18 and CX-2), growing in confluent and subconfluent monolayer cultures, as multicellular tumor spheroids and in nude mice, using the immunofluorescence technique (confocal microscopy) and flow cytometry. The fast-growing cell line HRT-18 expressed, in confluent and subconfluent monolayer cultures, alpha 2, 3 and beta 1 with a continuous membranous staining pattern, whereas alpha v, alpha 6, and beta 4 were expressed continuously membranous in the intermediate and apical part of the cell layer, and clustered at focal contacts at the base of the cells. In spheroids and tumors of nude mice the focal pattern of alpha v, 6 and beta 4 was changed into a diffuse one. Using flow cytometry, the expression of alpha 3 was found to be reduced in spheroids of HRT-18. The slowly-growing cell line CX-2 expressed, under the same conditions in monolayer culture, alpha 6, beta 1 and beta 4, and very weakly alpha 2, 3, 5 and v. Alpha 3 was expressed in spheroids of CX-2 only at the outer rim where the cells proliferate. In contrast, alpha 2 and 5 were expressed mainly in the quiescent, non-proliferating area. Alpha 6 was reduced in spheroids of CX-2. In the nude mouse tumor of CX-2, alpha 5 was expressed only focally and very weakly, alpha 2 was no longer detectable, but alpha v appeared to be enhanced in a focal pattern. These data indicate that integrin expression of tumor cells depends upon the culture system and that integrin expression in multicellular tumor spheroids is more similar to the in vivo situation in nude mouse tumors.

Animals↗

PubMed1995

Morphology of cardiac muscle in septic shock. Observations with a porcine septic shock model.

The morphology of cardiac muscle was investigated in a porcine model of septic shock, created by intermitted application of Escherichia coli-endotoxin. The earliest lesions, found after 18 h of septic shock, were endothelial cell swelling, marked leucostasis and slight ischaemic alterations of the muscle fibres. At the end point of the experiments, after 48 h, some fibrin thrombi were found associated with more pronounced ischaemic alterations of cardiac muscle cells and some necrotic fibres. Comparing these findings with the severe endothelial and muscle fibre lesions found in skeletal muscle, the endothelial cells of the heart microvasculature, are clearly more resistant to the attack of the endotoxins and mediators liberated in septic shock.

Animals↗

PubMed1995

Diagnostic imaging of mesenteric infarction.

PURPOSE: To determine the value of diagnostic imaging in the management of mesenteric infarction. MATERIALS AND METHODS: Within 8 years, 54 patients with mesenteric infarction underwent diagnostic imaging before surgery, including plain radiography (n = 45), ultrasound (US) (n = 29), small bowel follow-through examination (n = 7), colon enema study (n = 7), angiography (n = 16), and computed tomography (CT) (n = 22). Clinical course, laboratory values, and imaging findings were considered in diagnosis. RESULTS: Radiography and US allowed correct diagnoses in five of 18 cases (28%). Only one of 14 fluoroscopic examinations contributed to diagnosis. Fourteen of 16 angiography studies (sensitivity, 87.5%) and 18 of 22 CT examinations (82%) were correct. The difference in sensitivity between CT and angiography was not significant (P > .05). CONCLUSION: CT and angiography are highly sensitive, but CT can also be used to rule out other causes of acute abdomen. Careful evaluation of patient history and clinical situation should lead to suspicion of mesenteric ischemia and early indication for CT.

Aged↗

PubMed1995

Extracellular matrix proteins in colorectal carcinomas. Expression of tenascin and fibronectin isoforms.

BACKGROUND: Interactions of tumor cells and extracellular matrix (ECM) components are crucial determinants of tumor cell spreading and metastatic activity. Particularly tenascin (TN) as a member of the adhesion modulating family of ECM and its alternatively spliced isoforms became the matter of interest in ECM changes associated with malignancy. EXPERIMENTAL DESIGN: We analyzed the composition of the stromal- and basement membrane-associated ECM of colorectal adenomas and carcinomas using indirect immunofluorescence. Tenascin was investigated by immunoblot of snap frozen tumor specimens. RESULTS: Fibronectin (FN), TN, and chondroitin sulfate proteoglycan were the major components of the tumor stroma. Normal basement membrane components like laminin (LM), collagen type IV, and heparan sulfate proteoglycan were down-regulated. In the center of the tumor, tumor glands were surrounded by discontinuous basement membranes. At the tumor-host interface and in solid, poorly differentiated tumors, no immunoreactivity with normal basement membrane components was found. However, in cases with pericellular anti-LM staining, LM immunoreactivity was also found at the tumor-host interface. An alternatively spliced isoform of TN with a molecular weight of 330 kDa was found in seven of 15 carcinomas. In four of these cases, an alternatively spliced isoform of FN containing the ED-B segment was present. CONCLUSIONS: The coexpression of alternative splicing of FN and TN suggests that there may be common regulation mechanisms. The matrix composition found in the present study resembles that of healing wounds and probably favors the invasive spread of tumor cells.

Adenoma↗

PubMed1995

[Diagnosis of an infected thrombus of the inferior vena cava with ultrasound and computerized tomography].

The incidence of central venous catheter-associated thrombosis is up to 66%; nevertheless, in most cases it is of little clinical importance. A rare, but serious complication is infection of a catheter-associated thrombosis, which occurs in 7-16%. We report the case of a 16-year-old male patient, who suffered from meningitis and Waterhouse-Friderichsen syndrome. After initial improvement in the intensive care unit, he developed septic temperatures, caused by an infected thrombus of a central venous catheter in the inferior vena cava. Color-coded ultrasound showed hyperechogenic signals and missing flow detection at the catheter tip. Computed tomography showed air bubbles in the thrombosed catheter tip and confirmed the diagnosis. Vascular surgery was done and an infected, 17-cm-long infected thrombus was removed. The recent literature on this topic is reviewed.

Adolescent↗

PubMed1994

Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model.

In domestic pigs, intermitted application of Escherichia coli-endotoxin was used to create an animal model for a prolonged hypo- and hyperdynamic septic shock-like state and to investigate mechanisms of multiple organ failure. Here, we describe the changes in skeletal muscle after 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions instead of endotoxin served as controls. The earliest lesions were endothelial cell damage with endomysial oedema and swelling of mitochondria in muscle fibres. With increasing degree of endothelial cell damage, pericytes showed degenerative changes with cytoplasmic fragmentation and karyolysis. After 48 h of shock, endomysial oedema was increased with fibrinogen present. Muscle fibre diameters were increased and swollen mitochondria and segmental necrosis of muscle fibres were frequently observed. However, phagocytic reaction or regenerative changes were not detected. In this respect, skeletal muscle lesions in septic shock differ from ischemic damage, which is characterized by early phagocytosis. Tumour necrosis factor alpha (TNF alpha) was increased greatly and significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle fibres by the endotoxin and/or the increased levels of TNF alpha and indirect damage because of the increased diffusion distance, due to the endomysial oedema. The loss of blood proteins into the endomysium may also play a role in generating hypoproteinemia in patients with septic shock.

Animals↗

PubMed1994

Association of different macrophage phenotypes with infiltrating and non-infiltrating areas of tumor-host interface in colorectal carcinoma.

At the tumor-host interface (interface) of well differentiated tubulary or tubulopapillary colorectal carcinomas infiltrative, poorly demarcated and non-infiltrative, well bordered areas alternate. The composition of the inflammatory infiltrate within the desmoplastic stroma of the central tumor part and the interface was analyzed, particularly emphasizing differences between infiltrative and non-infiltrative areas of the interface. Of particular interest was the distribution of the following recently identified, functionally different human macrophage phenotypes: the 27E10-positive phenotype, an inflammatory macrophage, the 25F9-positive phenotype, a mature, resident macrophage and the RM3/1-positive phenotype, associated with anti-inflammatory function. It was found that macrophages were the dominating cells in the inflammatory infiltrate of both central tumor part and interface and that the number of B-cells and NK-cells were negligible. The 27E10-positive phenotype revealed a strong association with infiltrative areas at the interface, whereas the resident macrophage together with the RM3/1 was associated with sharply bordered tumor areas dominating within the tumor stroma, particularly in carcinomas with marked desmoplastic stroma response. These findings suggest that different macrophage phenotypes, localized in different regions of the carcinoma, have different effects on tumor cells.

Adenoma↗

PubMed1994

Differential adherence of the human monocyte subsets 27E10 and RM3/1 to cytokine- or glucocorticoid-treated endothelial cells.

Monocyte-endothelial interactions are of particular importance in the regulation of inflammation. The aim of the present study was to investigate the adhesion of functional different monocyte subsets to human umbilical vein endothelial cells treated with various cytokines or a glucocorticoid. The adherence of monocyte subset 27E10, which is associated with inflammatory processes, increased after endothelial activation with interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNF alpha), and the glucocorticoid prednylidene (Pred). The adherence at IFN gamma-treated endothelial cells was strong after a coculture duration of 10 min with a slight increase up to 60 min. The peak value after TNF alpha stimulation was reached after 15 min, thereafter quickly decreasing. IL-1 and Pred treatment caused a maximal adherence between 15 and 30 min followed by a slow decrease. TNF alpha and particularly interleukin-6 (IL-6) enhanced the endothelial adhesion of the monocyte subtype RM3/1, which is associated with the downregulation of inflammation. The maximal adherence was found after 15 and 30 min of coculture, respectively. The results show that, through modulation of the adhesive properties of endothelial cells, cytokines and glucocorticoids affect the adherence of monocyte subsets differently. They also suggest that IL-6 plays a role in the downregulation of acute inflammation.

Cell Adhesion↗

PubMed1993

Interaction of human malignant melanoma tumor spheroids with endothelium and reconstituted basement membrane: modulation by RGDS.

Tumor-cell extravasation involves sequential adhesive interactions with vascular endothelium and the subendothelial basement membrane. We have established a 3-dimensional model in vitro to simulate these events and to elucidate targets of the anti-cell-adhesive synthetic peptide RGDS. Tumor spheroids of the melanoma cell line ST-ML-12 served as models of tumor-cell emboli and were transferred onto human umbilical vein endothelial cells. To imitate the vascular anatomy, the latter were grown on reconstituted basement membranes produced by dextran-stimulated bovine corneal endothelial cells. RGDS did not affect the homotypic aggregation of the tumor cells and only minimally inhibited the attachment of the spheroids to the reconstituted vessel. A short-term (20 min) inhibition of adhesion to denuded basement membranes was observed. The attachment was closely associated with damage to the endothelial cells by oxygen-derived free radicals. RGDS retarded endothelial injury for up to 3 hr. The most prominent effect was observed after penetration of the endothelium. RGDS suppressed the emigration of tumor cells from the attached tumor-cell cluster in a dose- and time-dependent fashion. After 12 hr, the inhibitory effect progressively declined. This was not due to loss of activity of the peptide, indicating a resistance mechanism in the melanoma cells. On purified components of the basement membrane, RGDS effectively inhibited the initial spheroid attachment to fibronectin and collagen IV but had no effect on attachment to laminin. By contrast, subsequent migration was significantly suppressed on all substrata. Our model permits the study of dynamic cell-cell and cell-extracellular-matrix interactions and indicates that RGDS might predominantly act on early tumor-cell locomotion after penetration of the endothelium.

Basement Membrane↗

PubMed1993

[Septic shock and multiple organ failure in surgical intensive care. An animal experiment model on the analysis of pulmonary and intestinal dysfunction].

The study deals with an animal model for the problems of surgical intensive care patients. Following repeated applications of E. coli endotoxin WO 111:B4 under standard conditions, specific hemodynamic and biochemical (TNF, TXA2, PGI2, IL-6, PAF) and morphological (endothelium of the lung) alterations were detected. ARDS patterns induced by the sepsis were analyzed by high-frequency measurement of pressure and flow (385 measurements per breathing cycle). The role of the intestine in sepsis was investigated by ion-selective monitoring of surface potassium activity comparing mucosa and serosa. Every injection of endotoxin was followed by a selective increase of the potassium activity revealing relative ischemia induced by the endotoxin. The profile of the potassium levels on the surface correlates both with the cardiac output and with the prostacyclin levels. The continuous narrowing of the difference between mucosa and serosa, potassium during the period of investigation can be regarded as evidence for pathologic change in permeability fostering the septic course.

6-Ketoprostaglandin F1 alpha↗