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Biomedical subjects

T Schilling

Publications and source records attributed to T Schilling.

71 records · Page 4Linked to original sources

Does immobilization influence the systemic acceleratory phenomenon that accompanies local bone repair?

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as the regional acceleratory phenomenon (RAP). We previously showed that restoration of a local bone defect in the rat leads not only to RAP but also leads to a systemic acceleration of osteogenesis (systemic acceleratory phenomenon, SAP) in distant sites of the skeleton. In this study we investigated the impact of immobilization of the defect-bearing extremity on the development of SAP. A hole 1.2 mm in diameter was drilled in the diaphysis of the left tibia of female rats. In the experimental group (n = 15), a knee tenotomy was performed in the defect-bearing left hind leg. We examined both femora, both tibiae, and the fourth lumbar vertebra by computed x-ray densitometry on day 7 postoperatively. Immobilization of the defect-bearing limb led to a decrease in x-ray density not only of the immobilized (p < 0.0001) but also of the contralateral tibia (p < 0.0001). Both femora (p < 0.001) and the fourth lumbar vertebra (p < 0.025) of the experimental group also showed a significant decrease in x-ray density. We previously showed that SAP leads to an increase in x-ray density of both femora. This increase is no longer detectable in animals after immobilization of the defect-bearing limb. Thus we conclude that immobilization interferes with SAP. This suggests the possible dependence of SAP on mechanical load. Furthermore, these data suggest a possible impact of local immobilization on the rest of the skeleton.

Absorptiometry, Photon↗

Mineral apposition rate in rat cortical bone: physiologic differences in different sites of the same tibia.

The mineral apposition rate (MAR) is a commonly used parameter for the characterization of bone formation and is often determined to test for experimental effects on cortical bone. We investigated whether there are physiologic variations in rat cortical MAR dependent on the side or site of measurement. In our experiment we used female rats. The animals were sacrificed on day 8, after double-fluorochrome labeling with calcein and tetracycline was performed. The MAR was calculated at 3.6, 5.4, 7.2, 9, and 10.8 mm from the epiphyseal growth plate of the lateral as well as of the medial endosteum of both right and left tibiae. We found a physiologic significant difference in the MAR between the lateral and the medial endosteal sites of the same tibia (p < 0.0001), especially near the epiphyseal growth plate. Regarding the same cortical side, there is a significant decrease (p < 0.0001) in the endosteal MAR with increasing distance from the epiphyseal growth plate. We conclude that the observed differences in endocortical MAR must be due to specific mechanical challenges. Because these differences are statistically significant, it is necessary to standardize the area of histomorphometric measurement not only with respect to the distance from the epiphyseal growth plate, but also with respect to the cortical side.

Analysis of Variance↗

The perception of identity by 6 1/2-month-old infants.

In Study 1, sixteen 6 1/2-month-olds were habituated to a Reversible stimulus (an upright face that could be perceived as an entirely different upright face when it was rotated 180 degrees) and to a Nonreversible stimulus (a face that could be perceived as upright in only one orientation). Following habituation for each type of stimulus, test trials paired the habituated face with a novel stimulus (an inversion of the same face). For both Reversible and Nonreversible stimuli, the physical difference between the old and new test stimuli was the same (a 180 degrees rotation); however, infants devoted more visual attention to the 180 degrees rotation only when it was a Reversible face, suggesting that the identity change was detected. Experiment 2 ruled out the explanation that infants might have failed to dishabituate to the inversion of the Nonreversible stimulus because they could not remember it. Results are interpreted as evidence that 6 1/2-month-old infants are not limited to face recognition based on similarity in pattern arrangement alone, but are capable of processing faces at a representational level.

Attention↗

Endotoxin-neutralizing capacity of soluble CD14.

Luminol-enhanced chemiluminescence was used to determine the effect of soluble CD14 (sCD14) on the endotoxin-inducible generation of reactive oxygen species in human monocytes. It was necessary to mediate lipopolysaccharide (LPS) monocyte-activating capability by serum factors (LPS-binding proteins). sCD14 reduced LPS-inducible monocyte activation in a dose-dependent manner, even in the case of CD14- monocytes, obtained from a patient with paroxysmal nocturnal haemoglobinuria. These monocytes could be activated by opsonized LPS via other receptors. Using anti-mouse Ig-coated microbeads, it was demonstrated in FACS analysis that sCD14 mediates the binding of a mouse monoclonal anti-CD14 antibody (RoMo 1) to a complex of LPS/FITC (fluoroisothiocyanate) and a LPS-binding protein. The release of sCD14 from cultured monocytes was measured using LPS, TNF alpha (tumour necrosis factor), IL1, 4 and 6 (interleukin-1, -4 and -6) and IFN gamma (interferon-gamma) as stimulators. Addition of LPS and TNF alpha led to a dose-dependent increase in sCD14-levels in the culture supernatant, whereas IL1, IL6 and IFN gamma had no significant effect. IL4 dose-dependently depressed spontaneous sCD14 release. It is possible that elevated sCD14-serum levels in polytraumatized patients indicate a natural protective mechanism against excessive monocyte mediator production. Therefore, sCD14 may be a new therapeutic concept in endotoxic shock prevention.

Antigens, CD↗

A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat.

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP. SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP.

Absorptiometry, Photon↗

sCD14 prevents endotoxin inducible oxidative burst response of human monocytes.

Luminol-enhanced chemiluminescence (LECL) was used to determine the effect of soluble CD14 (sCD14) on the endotoxin inducible generation of reactive oxygen species in human monocytes. LPS is unable to activate monocytes under serum free conditions, but LECL responses were measured after pretreatment of LPS stock solution with serum, according to Wright et al., who described a LPS-binding protein (LBP), necessary for mediating LPS binding to the receptor CD14 on monocyte surfaces. In normal human serum a soluble form of CD14 (sCD14) exists, from which nothing is known about its possible function. sCD14 reduces the endotoxin inducible monocyte activation in our in vitro model in a dose dependent manner (5-30 micrograms/ml) suggesting an immunomodulatory function. Therefore it seems to be a new candidate for a therapeutic concept in endotoxic shock prevention.

Antigens, CD↗

Direct evidence of a functional separation of alloreactive T lymphocytes from bystander cells infiltrating rat allografts. Interleukin 2 receptor-positive cells reacting with the monoclonal antibody ART 18 mediating second-set rejection.

In this study we examined the functional capacity of unseparated, IL-2R positive and IL-2R negative leukocytes infiltrating BN rat hearts or kidneys grafted into allogeneic LEW rats. Upon adoptive transfer into syngeneic LEW recipients, splenocytes or day-3 graft infiltrate cells of either cardiac or renal transplants were ineffective to alter BN cardiac test graft survival (controls 7.8 +/- 0.8 day). However, adoptive transfer of day-5 heart infiltrate cells resulted in a delay of test graft rejection (9.4 +/- 0.7 day, P less than 0.001), while day-5 kidney-graft-infiltrating cells produced second set rejection (6.2 +/- 0.5, P less than 0.001). Specificity controls of day-5 cells infiltrating DA heart or kidney grafts rejected at 7.8 +/- 0.8 or 7.7 +/- 0.5 days. Following separation into IL-2R positive and negative subpopulations by use of the mAB ART 18, IL-2R positive but not IL-2R negative cells caused second set rejection in both the renal and the cardiac model (6.2 +/- 0.4, respectively, 6.3 +/- 0.5 days, P less than 0.001 or P less than 0.005). Furthermore, in the kidney model IL-2R positive nylon-wool nonadherent cells also caused second set rejection (6.2 +/- 0.4, P less than 0.005) suggesting that IL-2R positive T cells present in the graft at maximal infiltration are the mediators of rejection. Thus, it appears that these cells can be phenotypically and functionally separated from bystander cells.

Animals↗

[Sonographic differential diagnosis of extrahepatic cholestasis].

The value of sonography for aetiological diagnosis was examined in 196 patients with extrahepatic cholestasis. For each patient a diagnosis was prospectively worked out by sonography and compared with the true diagnosis established by endoscopic retrograde pancreaticocholangiography (ERCP), and/or computed tomography (CT), surgical intervention, autopsy and unequivocal clinical course. In 72 patients cholangiolithiasis was the cause of the obstruction. It was diagnosed by sonography with a sensitivity of 86% and a specificity of 93%. With 25 patients with another benign cause of cholestasis the diagnosis was made by sonography in 23 cases. In 93 patients the underlying malignant disease was recognised sonographically with a sensitivity of 95% and a specificity of 100%.

Adult↗

[Experience in endoscopic retrograde cholangio-pancreaticography with Peritrast 400 comp (author's transl)].

In 210 cases of endoscopic retrograde cholangio-pancreaticography (ERCP), Peritrast 400 comp was used as contrast medium. The good tolerence and low rate of complication associated with this preparation despite the higher contrast medium concentration were remarkable. On the whole, only one severe complication was observed, namely, an abscess-forming pancreatitis. This could be controlled by conservative treatment.

Cholangiography↗

[Double-contrast technique for diagnostics of the large intestine (author's transl)].

The results of 1300 radiographic examinations of the colon with the double-contrast method were reported. In preparation for the examination, only a laxative (cascara salax) was administered and the patient not permitted to eat. The importance of horizontal films was mentioned in particular. A malignant tumor in the colon was discovered in 137 cases. A malignant degeneration was established via histologic examination in 23 of the 152 patients with polypoid lesions. Juxtaposition of a malignant tumor and a polypoid lesion or a second carcinoma was discovered via radiological examination in 28 patients.

Adult↗

Diagnostic image workstations for PACS.

Image workstations will be the 'window' to the complex infrastructure of a PACS with its intertwined image modalities (image sources, image data bases and image processing devices) and data processing modalities (patient data bases, departmental and hospital information systems). They will serve for user-to-system dialogues, image display and local processing of data as well as images. Their hardware and software structures have to be optimized towards an efficient throughput and processing of image data.

Hospital Information Systems↗

Human monocytes lacking the membrane-bound form of the bacterial lipopolysaccharide (LPS) receptor CD14 can mount an LPS-induced oxidative burst response mediated by a soluble form of CD14.

Monocytes and macrophages express a glycosyl phosphatidylinositol (GPI)-anchored lipopolysaccharide (LPS) receptor on the cell surface which enables them to detect minute amounts of LPS released from Gram-negative bacteria. A soluble form of CD14 is also found free in serum, though its physiological function is unknown. the interaction of LPS with CD14 on the monocyte surface leads to an activation of the cells which is manifested in the sudden release of reactive oxygen species, a process referred to as an oxidative burst. In patients suffering from the condition known as paroxysmal nocturnal haemoglobinuria (PNH), the synthesis of GPI anchors is blocked in haematopoietic cells which are therefore unable to express GPI-linked proteins on their surface. In severe cases, over 90% of monocytes lack membrane-bound CD14, though normal levels of the soluble form of the receptor-sCD14-are found in the serum. Despite this lack of membrane-bound CD14, monocytes from PNH patients can respond to low concentrations of LPS. Here we show that the LPS-induced oxidative burst of these PNH monocytes requires a component present in serum. The serum-dependent activation can be inhibited by monoclonal antibodies to CD14, can be removed from the serum by passage over a matrix to which an anti-CD14 antibody has been bound, and the depleted serum can be reconstituted by the addition of either purified natural or purified recombinant soluble CD14. We conclude that an LPS-dependent oxidative burst in PNH monocytes can be mediated by soluble CD14.

Acute-Phase Proteins↗

Paclitaxel administered over 3 h followed by cisplatin in patients with advanced head and neck squamous cell carcinoma: a clinical phase I study.

We have performed a clinical phase I trial of a combination treatment with paclitaxel given as 3-hour infusion and cisplatin to determine the maximum tolerated dose and the dose-limiting toxicity in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Treatment was repeated every 21 days. Doses administered ranged from 135 mg/m2 paclitaxel/75 mg/m2 cisplatin to 250 mg/m2 paclitaxel/100 mg/m2 cisplatin. Twenty-four patients have been entered into this study. The maximum tolerated dose was determined to be 225-250 mg/m2 paclitaxel/100 mg/m2 cisplatin. The dose-limiting toxicity of this regimen was myelosuppression (granulocytopenia). Neurosensory and neuromotor toxicity was moderate. However, analyses of threshold electrotonus studies indicated subclinical neurotoxicity in most patients. One patient receiving 200 mg/m2 paclitaxel/100 mg/m2 cisplatin developed grade 3 motor-neurotoxicity. Orthostatic hypotension was observed in 8 patients receiving doses of 200 mg/m2 paclitaxel/100 mg/m2 cisplatin or higher. Objective responses were observed at paclitaxel 175 mg/m2/ cisplatin 100 mg/m2 (n = 5; complete response in 1 patient), paclitaxel 200 mg/ m2/cisplatin 100 mg/m2 (n = 3; partial response in 3 patients) and at paclitaxel 225 mg/m2/cisplatin 100 mg/m2 (n = 8; partial response in 1 patient). Eleven additional patients had stable disease. We conclude that paclitaxel administered as a 3-hour infusion followed by cisplatin is an active regimen in advanced head and neck cancer and that orthostatic hypotension may be a potentially significant clinical toxicity.

Adult↗