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Biomedical subjects

B Klosterhalfen

Publications and source records attributed to B Klosterhalfen.

At least 109 records · Page 6Linked to original sources

Computed tomography and histologic results in the early stages of endotoxin-injured pig lungs as a model for adult respiratory distress syndrome.

RATIONALE AND OBJECTIVES: To determine early radiographic changes in diffuse alveolar injury, the authors correlated computed tomography (CT) and histopathology in pigs with recurrent endotoxinemia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Animals↗

[Lymphocyte defects in chronic osteomyelitis. A prospective study].

In patients with chronic post-traumatic osteomyelitis, several deficits in immunological response were demonstrated. In a prospective trial of 20 patients with proven osteomyelitis, histological analysis of lymphocyte subsets in peripheral blood and in the infected bone tissue was performed. The effects of chronic osteomyelitis on lymphocyte subsets in the peripheral blood and in inflamed tissue were only slight. The T4/T8 ratio was diminished in only two patients and had no relationship to the clinical course. Interleukin 2 receptor determination was negative in 83% of biopsies of infected tissue. Osteomyelitis may possibly cause a defect in lymphocyte/macrophage cooperation.

Adolescent↗

Macrophages and multicellular tumor spheroids in co-culture: a three-dimensional model to study tumor-host interactions. Evidence for macrophage-mediated tumor cell proliferation and migration.

In a new co-culture model involving multicellular tumor spheroids and different phenotypes of human macrophages, we studied the effects of the latter on migration and proliferation of the human colon carcinoma cell line, HRT-18. The macrophage phenotypes are detectable with monoclonal antibodies and are inducible in culture. 12-O-tetradecanoyl-phorbol-13-acetate-activated macrophages are associated with the phenotype 27E10, which is an acute inflammatory macrophage. The glucocorticoid-induced macrophage phenotype RM3/1 is associated with the down-regulation of inflammation. The phenotype resembling the mature resident macrophage termed 25F9 arises spontaneously in prolonged culture. It could be shown that inflammatory macrophages are localized at invasive areas of the tumor-host interface of colorectal carcinoma, whereas resident and anti-inflammatory macrophages were found in the central tumor region or at well-bordered areas of the tumor-host interface. The results obtained with this co-culture model show that 27E10-associated macrophages stimulate tumor cell migration and inhibit tumor cell proliferation. RM3/1 had only a slight inhibiting effect on proliferation and a slight promoting effect on migration. The 25F9-positive macrophage-stimulated tumor cell proliferation and inhibited migration completely. This investigation indicates that this in vitro system is useful for studying different macrophage effects on tumor cells and that indeed proliferation and migration of tumor cells could be influenced in an opposite manner by different types of macrophages.

Carcinoma↗

Time course of various inflammatory mediators during recurrent endotoxemia.

The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators.

6-Ketoprostaglandin F1 alpha↗

[Endoscopic therapy of benign anastomotic stenoses in the area of the colon and rectum by electro-incision and balloon dilatation].

21 patients with a severe anastomotic stenosis in the colorectal region were treated with hydraulic balloon dilatation and endoscopic electro-incision. The severity of symptoms directly correlates with the extent of stenosis (degree I phi 13 mm, n = 12; degree II phi 7 mm, n = 6; degree III phi 4 mm, n = 3). All patients with a stenosis of degree I and II were symptom-free after the endoscopic therapy. In 2 of 3 cases the symptoms of stenosis of degree III could clinically be improved after the treatment. The average frequency of dilatation was 1.5 x, complications such as bleeding or perforation were not registered. Animal studies explain anastomotic stenosis through an increased submucosal formation of collagen fibers followed by formation of scars in the anastomosis. The efficiency of electro-incision and balloon dilatation is based on an increased diameter in the anastomotic region without increased formation of new collagen fibers.

Adult↗

[Differential surgical therapy in diffuse peritonitis].

96 patients were operated on for diffuse peritonitis from January 1986 to June 1990. They underwent a differentiated therapeutical concept according to the severity of the underlying peritonitis. Mild forms were handled with the standard approach, while mid-severe cases were treated by continuous postoperative peritoneal lavage. Patients with severe peritonitis were operated on by open abdomen management. Mortality was 32% (31/96) and with that obviously better than the statistically expected mortality, based on the Mannheim-Peritonitis-Score (49%). The same findings could be demonstrated in the therapeutic subgroups. The management of diffuse peritonitis using such a differentiated surgical concept seems to be an effective approach to reduce mortality rates.

Adolescent↗

Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals.

Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical-scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma.

Cell Communication↗

Characterization of the new bladder cancer cell line HOK-1: expression of transitional, squamous and glandular differentiation patterns.

The new continuous cell line HOK-1 derived from a grade-III transitional-cell bladder carcinoma with foci of squamous and glandular differentiation was shown to retain this phenotypical heterogeneity for more than 45 passages in vitro. Electron microscopy revealed transitional as well as a considerable proportion of squamous carcinoma and adenocarcinoma cells. PAS-positive mucus was detected in numerous cells. These features were principally maintained when grown as multicellular spheroids and in nude mice. More pronounced signs of differentiation (i.e., expression of cytokeratins 10 and 11, formation of glandular structures) were found in xenograft tumours. Independently, cytokeratins 13, 18 and 19 were detected in vitro and in vivo, reflecting the urothelial origin. The line forms distinct colonies in soft agar, expresses Lewis-x and Lewis-y antigens and reacts with monoclonal antibodies (MAbs) against CEA, beta-HCG and URO-5. Cytogenetic analysis revealed several related clones with a rearrangement at chromosome 1 and loss of one X chromosome as common karyotypic changes in all clones. DNA content, as quantified by image analysis, showed a DNA stemline close to 2c. The new cell line HOK-1 can be used as an in vitro model to study the mechanisms of heterogeneous differentiation patterns in bladder cancer.

Aged↗

Anatomic nature and surgical significance of anal sinus and anal intramuscular glands.

The nature of anal sinus and anal intramuscular glands is well known, but their origin is still discussed. In the past years a surprising new theory about the invagination of the proctodeum into the hindgut was put forward. Evidence supporting this theory would be the existence of an "anorectal band" and "epithelial debris" in the subanoderm formed during total or partial obliteration of the anal sinuses. To characterize these histological structures, the authors examined 62 autopsy specimens with conventional and special immunohistologic staining methods. In none of the examined specimens could the structures mentioned above be detected. Nearly 90 percent of our specimens contained the well known anal sinuses. In fetuses, neonatal deaths, and children, more than one-half of the anal sinuses were accompanied by anal intramuscular glands penetrating the internal anal sphincter, whereas in adult specimens the anal intramuscular glands were rare. Eight postoperative, idiopathic chronic anal fissures and three postoperative anal fistulas examined with the same staining procedures showed epithelial cells at the base of the fissures or fistulas in two cases (25 percent) and three cases (100 percent), respectively. The results reinforce the theory that anal sinuses and anal intramuscular glands are separate anatomic entities and indicate a new theory of anal development. For idiopathic, chronic anal diseases anal sinuses have little surgical significance. Anal intramuscular glands should be the anatomic correlate of anal fistulas.

Adolescent↗

Fibrinogen degradation product-D, fibrinogen, and serum change polymorphonuclear granulocyte activity--possibly important post-trauma?

Severe trauma favors the susceptibility of patients to infection. It has been shown that proteins or protein fragments are responsible for an endogenous immunodepression. After trauma a coagulopathy accompanied by increased serum levels of fibrinogen degradation products (FDP) is often found. Therefore, we examined whether FDP-D can influence the activity of polymorphonuclear neutrophils (PMN). PMN-activation was measured by two different superoxide-specific methods (Cytochrome-C-test, INT-test). With both methods we found a decrease of PMN activity by FDP-D compared to fibrinogen. Albumin, which was used as a control protein, only influenced PMN activity in unphysiologically high concentrations. The third method used to quantify PMN activity was chemiluminescence, which is a more unspecific method since it is developed not only by oxygen radical species but also by activating the lipoxygenase pathway. In contrast to the superoxide specific tests we found an inhibitory effect of fibrinogen and also serum compared to FDP-D using chemiluminescence.

Cytochrome c Group↗

[Effects of a defined infusion of 10% HAES 200/0.5 in the early phase of a septic syndrome on hemodynamic parameters].

In an animal model the hemodynamic effects of three infusions of HES during the early stage of a septic syndrome were examined. In nine pigs with a body weight between 29 and 36 kg a septic syndrome was produced by infusion of E. coli endotoxin. 1, 4 and 7 hours after beginning of the endotoxin infusion 250 ml HES 200/0.5 were infused. After the 1st and 3rd infusion an increase of the cardiac output resulted, which was previously lowered, without changes of the CVP. During normal CO the 2nd infusion shows an increase of CVP and MAP. PWP did not change. The reactions of the hemodynamic parameters can be well explained physiologically. A volume supply at a reduced CO increases the latter without influence of the CVP. Normalized CO before the infusion resulted in a CVP-increase. The PWP is not evaluable under the conditions of an elevated pulmonary resistance, as it exists at the septic syndrome.

Animals↗

Hemodynamic variables and plasma levels of PGI2, TXA2 and IL-6 in a porcine model of recurrent endotoxemia.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.

Animals↗

[Jejunal diverticulosis--a rare cause of gastrointestinal hemorrhage].

We report a case of gastro-intestinal bleeding caused by jejunal diverticulosis, in which preoperative diagnosis could be achieved by selective angiography. Even though the small bowel is a rare localisation of bleeding (1% of all cases), this part of intestine should be included into diagnostic considerations. Jejunal diverticulosis only requires operative treatment after occurrence of complications, small bowel resection is regarded as treatment of choice in these cases.

Aged↗

Sclerosis of the internal anal sphincter--a process of aging.

Functional and organic alterations such as sclerosis of the internal anal sphincter muscle are often discussed as a cause of proctologic diseases. Systematic histopathologic examinations of this muscle are rare, although the internal anal sphincter is of primary significance for the continence of the anal canal and its functional efficiency. The authors believe that the degree of formation of connective tissue in this unstriated muscle depends on the age of the examined specimen. The authors can demonstrate that sclerosis is a physiologic process of aging.

Aging↗

Topography of the inferior rectal artery: a possible cause of chronic, primary anal fissure.

The authors believed that it might be possible to explain the local frequency of the anal fissure at the posterior commissure by an anatomic relationship, and examined the blood supply of the anus. The inferior rectal artery is demonstrated by postmortem angiography and by manual preparations (N = 41) and histologic study after angiography of the vessels (N = 10). The blood supply at the different sites of the anal canal are demonstrated by a morphometric study (N = 20). The inferior rectal artery presents two variants in the postmortem angiographies, type 1 (85.4 percent) and type 2 (14.6 percent). In type 1, the posterior commissure is less perfused than the other sections of the anal canal. In addition, the blood supply may be more compromised by contusion of the vessels passing vertically through the muscle fibers of the sphincter ani internus muscle during increased sphincter tone. The role of topography in the pathogenesis of the primary anal fissure is illustrated in a model.

Anal Canal↗