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Biomedical subjects

C Weiler

Publications and source records attributed to C Weiler.

At least 19 recordsLinked to original sources

[New bone formation by extracorporeal shock waves. Dependence of induction on energy flux density].

BACKGROUND: The purpose of this study was to test the hypothesis that shock waves can induce new bone formation even without cortical fractures and periosteal detachment as suggested in the literature. METHODS: Extracorporeal shock waves with energy flux densities between 0 mJ/mm(2) (sham treatment) and 1.2 mJ/mm(2) were applied in vivo to the distal femoral region of rabbits (1500 pulses at 1 Hz frequency each). Oxytetracycline was injected on days 5-9 and the animals were sacrificed on day 10. Sections of both femora of all animals were investigated with broadband fluorescence microscopy and contact microradiography for new periosteal and endosteal bone, periosteal detachment, cortical fractures, and trabecular bone with callus. RESULTS: Shock waves with energy flux densities of 0.9 mJ/mm(2) and 1.2 mJ/mm(2) resulted in new periosteal bone formation in the presence of cortical fractures and periosteal detachment. After application of shock waves with energy flux density of 0.5 mJ/mm(2), clearly detectable signs of new periosteal bone formation were observed without cortical fractures or periosteal detachment. CONCLUSIONS: The results of this study challenge the current view in the literature that the creation of cortical fractures and periosteal detachment are prerequisites for new bone formation mediated by extracorporeal shock waves.

Animals↗

2002 SSE Award Competition in Basic Science: expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption.

During the process of degeneration, the intervertebral disc (IVD) shows a progressive and significant reduction in height due to tissue resorption. Intradiscal clefts and tears are major hallmarks of disc degeneration. Matrix-degrading enzymes such as matrix metalloproteinases (MMPs) are assumed to play a pivotal role in disc tissue degradation and resorption. The objective of this study was therefore to investigate the potential role of MMPs in extracellular matrix degradation leading to disc degeneration. This study was conducted on 30 formalin-fixed and EDTA-decalcified complete cross-sections of lumbar IVDs from cadavers of individuals aged between 0 and 86 years. Tissue sections were used for the immunolocalization of MMPs-1, -2, -3 and -9. The number of labeled cells was assessed by morphometric analyses, and was statistically correlated with the formation of clefts and tears, cellular proliferation, granular matrix changes and mucous degeneration. Furthermore, 30 disc specimens obtained during spinal surgery were used for in situ hybridization of MMP-2 and -3-mRNA. In addition, the enzymatic gelatinolytic activity was determined by in situ zymography in autopsy material. Immunohistochemistry showed the intradiscal expression of all four MMPs, which was confirmed by in situ hybridization, providing clear evidence for the synthesis of the enzymes within nucleus pulposus and annulus fibrosus cells. Gelatinolytic enzymatic activity was verified by in situ zymography. IVDs from infants and young adolescents remained almost completely unlabeled for all MMPs tested, while more MMPs-1 and -3 were seen in disc cells of younger adults than in those of a more advanced age; MMP-2 remained unchanged over the adult age periods, and MMP-9 was expressed in only relatively few cells. This pattern significantly correlated with the occurrence of clefts and tears. This correlation was strongest for MMP-1 ( P<0.0001), MMP-2 ( P<0.0017) and MMP-3 ( P<0.0005) in the nucleus, and MMP-1 ( P<0.0001) and MMP-2 ( P<0.038) in the annulus. In parallel, the proliferation of disc cells and matrix degeneration (granular changes and mucous degeneration) were related to MMP expression. Likewise, enzymatic activity was seen in association with cleft formation. Our data suggest that major MMPs play an important role in the degradation of the IVD. This is evidenced by the high correlation of MMP expression with the formation of clefts and tears. These findings implicate a leading function for MMPs in IVD degeneration resulting in the loss of normal disc function, eventually leading to low-back pain.

Adolescent↗

Influence of extracorporeal shock-wave application on normal bone in an animal model in vivo. Scintigraphy, MRI and histopathology.

There is little information about the effects of extracorporeal shock-wave application (ESWA) on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm2 and 0.9 mJ/mm2 EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm2). One day after ESWA with 0.9 mJ/mm2 EFD but not with 0.5 mJ/mm2, there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm2 and 0.9 mJ/mm2 EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm2 EFD on periosteal soft tissue and tissue within the bone-marrow cavity.

Animals↗

Peptide-based analysis of amino acid sequences important to the biological activity of eosinophil granule major basic protein.

Synthetic peptides corresponding to amino acid sequences in eosinophil granule major basic protein (MBP) were evaluated for cytotoxic activity toward K562 cells and for ability to stimulate basophil mediator release. Results obtained using 14 peptides spanning the 117-amino acid sequence of MBP in overlapping fashion indicated that the activities mapped to peptide sequences near the amino and carboxy termini of MBP. The activity of these regions was confirmed using two peptides corresponding to MBP residues 18-45 and 89-117. A 20-h incubation with 5 microM peptide 18-45 or peptide 89-117 caused approximately the same levels (>60%) of cytotoxicity in K562 cells as 5 microM MBP. Similarly, a 30-min incubation with peptides 18-44 and 89-117 stimulated basophil histamine release in a concentration-dependent manner over the range of 5-20 microM. The level of release stimulated by 20 microM peptide 89-117 approached that stimulated by 2 microM MBP. A 20 microM concentration of peptide 89-117 also stimulated leukotriene C4 (LTC4) production by the basophils. Neither peptide 18-45 nor peptide 89-117 was cytotoxic for basophils under the experimental conditions for histamine and LTC4 release, as determined by 51Cr release. These results indicate that two MBP peptide sequences, including one (89-117) that contains a unique carbohydrate-binding region, share the biologic activities of MBP.

Amino Acid Sequence↗

Impaired tensile strength after shock-wave application in an animal model of tendon calcification.

Extracorporeal shock-wave application facilitates dissolution of rotator cuff calcifications. Therefore, disappearance or disintegration of tendon calcifications by shock waves might be appropriate for any kind of tendon calcification. Here, shock waves with various energy flux densities were applied to the mineralized medial gastrocnemius tendon of turkeys as an animal model. After application of shock waves in vivo, with energy flux density of 0.6 mJ/mm(2), histologic examination and microradiography did not show dissolution or disintegration of tendon calcifications. After shock-wave application in vitro, even for energy flux density of 1.2 mJ/mm(2) neither dissolution nor disintegration of tendon calcifications were observed. Biomechanical testing revealed significant impairment of tensile strength following shock-wave application in vitro, with energy flux density of 1.2 mJ/mm(2), but not with 0.6 mJ/mm(2). These results are important for considerations of clinical extracorporeal shock-wave application on tendon calcifications, as well as on tendon ossifications.

Animals↗

In situ compressive stiffness, biochemical composition, and structural integrity of articular cartilage of the human knee joint.

OBJECTIVE: Reduction of compressive stiffness of articular cartilage has been reported as one of the first signs of cartilage degeneration. For the measurement of in situ compressive stiffness, a hand-held indentation probe has recently been developed and baseline data for macroscopically normal knee joint cartilage were provided. However, the histological stage of degeneration of the measured cartilage was not known. The purpose of this study was to investigate whether there is a relationship between the in situ measured compressive stiffness, the histological stage of degeneration, and the biochemical composition of articular cartilage. DESIGN: Instantaneous compressive stiffness was measured for the articular cartilage of 24 human cadaver knees. Additionally, biochemical composition (total proteoglycan and collagen content) and histological appearance (according to the Mankin score) were assessed for each measurement location. RESULTS: Despite visually normal surfaces, various histological signs of degeneration were present. A high correlation between Mankin score and cartilage stiffness was observed for the lateral patellar groove (R(2)=0.81), the medial (R(2)=0.83) and the lateral femoral condyle (R(2)=0.71), whereas a moderate correlation was found for the medial patellar groove (R(2)=0.44). No correlation was observed between biochemical composition and cartilage compressive stiffness. CONCLUSIONS: Our results are in agreement with others and show that the instantaneous compressive stiffness is primarily dependent on the integrity of the extracellular matrix, and not on the content of the major cartilage constituents. The high correlation between stiffness and Mankin score in mild osteoarthrosis suggests that the stage of cartilage degeneration can be assessed quantitatively with the hand-held indentation probe. Moderate and severe case of osteoarthrosis remains to be investigated.

Adult↗

Quantification of laser-induced cartilage injury by confocal microscopy in an ex vivo model.

BACKGROUND: The application of lasers in orthopaedic surgery is increasing. However, some investigators have reported that osteonecrosis may occur after laser meniscectomy. The objective of the present study was to evaluate the effect of laser wavelength and energy on cartilage injury in an ex vivo model. METHODS: Fresh bovine articular cartilage was exposed to either holmium:yttrium-aluminum-garnet (Ho:YAG) or erbium:YAG-laser (Er:YAG) irradiation. Both lasers were operated in a free-running mode and at a pulse-repetition rate of 8 Hz. The effect of laser treatment at several energy levels (Er:YAG at 100 and 150 mJ and Ho:YAG at 500 and 800 mJ) was examined. For each light source and energy level, ten cartilage samples were assessed by conventional histological analysis and by confocal microscopy. Thermal damage was assessed by determining cell viability. RESULTS: The extent of thermal damage demonstrated by confocal microscopy was much greater than that demonstrated by histological analysis. The extent of thermal injury after Ho:YAG-laser irradiation was much greater than that after Er:YAG-laser irradiation, which was associated with almost no damage. In addition, the ablation depth was greater after treatment with the Er:YAG laser than after treatment with the Ho:YAG laser. CONCLUSIONS: In the present study, histological analysis underestimated thermal damage after laser irradiation. In addition, our findings highlighted problems associated with use of high-power settings of Ho:YAG lasers during arthroscopic surgery.

Animals↗

Foreign-body reaction to silastic burr-hole covers with seroma formation: case report and review of the literature.

Because silastic material is one of the most commonly used biomaterials in modern medicine, the biocompatibility of these implants is still a source of long standing controversy. Though several studies have established silastic material as biologically inert, numerous authors have repeatedly described characteristic pathological tissue responses to silicone and its elastomeres. We report a case of foreign-body reaction to silastic burr-hole cover with successive formation of a seroma following resection of an olfactory groove meningioma. Within 30 days postoperatively, the patient developed a marked bulge in the glabbelar region. Histopathological examination revealed a seroma-like lesion obviously caused by a chronic inflammatory allergic reaction to the silastic burr-hole cover. Although the silicone-induced tissue damage clinically shows a wide variability and a conclusive model of pathogenesis is presently not available, the histopathological findings in some patients, in the form of granulomatous lesions and inflammatory cell response, might partly be due to an immunological reaction. Such a reaction has been previously described both clinically and experimentally, as detected in our patient. In addition, a review of the literature is given.

Adult↗

A radiation hybrid map of the zebrafish genome.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes. Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map to match them with mapped candidate genes and expressed sequence tags (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions, as well as for the dog, rat and mouse. For our map of the zebrafish genome, we used an existing RH panel and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.

Animals↗

Drug targeting and metabolic investigations of cryoprepared tumor cells with analytical electron energy loss spectroscopy.

Analytical electron microscopy is an ideal tool for holistic data acquisition on biological systems. The use of analytical electron microscopy for both, the investigation of micropharmacokinetic problems and metabolic studies, is becoming more and more important. Depending on the mode of investigation, it is possible to localize drugs and xenobiotics precisely in situ under optical control or to quantify their uptake and distribution in the corresponding target cells without disintegrating the cell or tissue material. In this paper, we present instructive examples for the application of analytical electron energy loss spectroscopy in transmission electron microscopy in order to investigate the cellular uptake and distribution of cisplatin and cyclophosphamide and the metabolic changes induced by an alteration in the extracellular calcium concentration in a holistic manner.

Animals↗

The use of neuromuscular blocking drugs in the intensive care unit: a US perspective.

Surprisingly little is known about the use of neuromuscular blockers (NMBs) in intensive care units (ICUs) in the USA. Recently, Klessig et al. surveyed anesthesiologists/intensivists in the USA and found that the 55% who responded used NMBs in the ICU in an average of 10 patients per ICU per month. Anxiolytics and analgesics were administered concomitantly with NMBs, but a majority of respondents did not use electrophysiologic measures of the degree of blockade. Another survey of predominantly medical ICUs also demonstrated widespread use of NMBs, but internists did not use sedation/analgesia as frequently as anesthesiologists for patients receiving NMBs, and infrequently monitored the degree of neuromuscular blockade. Because these were retrospective surveys, we decided to monitor prospectively the use of NMBs in our ICUs. The use of NMBs was ascertained by daily review of pharmacy records and, when use was documented, the patients' hospital records were reviewed. Where information was missing or not found, attending physicians were interviewed. On average, one patient per month per ICU received NMBs. Approximately 5% of neonatal and pediatric, and 1% of adult, ICU patients received NMBs. Eighty-three percent of patients received NMBs to facilitate mechanical ventilation, and mortality was high (51%) in those critically ill patients. More than half the patients were treated for < or = 24 h, the remainder for 2 days to > 3 weeks. Twitch monitors were used for monitoring the degree of neuromuscular blockade in adult patients, and all patients received sedatives/analgesics. We estimated that the risk of clinically significant, prolonged neuromuscular blockade following the discontinuation of NMBs was 5% per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increased prostaglandin PGE2 and 6-keto-PGF1 alpha immunoactivity in incubates of gastric mucosa and forestomach of nephrectomized rats.

Prostaglandin E2 (PGE2)- and 6-keto-PGF1 alpha-like immunoactivity was measured in incubates of forestomach and gastric corpus mucosa in (a) unoperated rats, (b) rats with sham-operation of the kidneys and (c) rats with bilateral nephrectomy. In addition the mean ulcer area in the forestomach and gastric mucosa was assayed in all three groups of rats. The PGE2- and 6-keto-PGF1 alpha-like immunoactivity in gastric mucosa incubates and 6-keto-PGF1 alpha in the forestomach incubates was almost the same in unoperated and sham-operated rats. Increased 6-keto-PGF1 alpha in the forestomach and of PGE2 and 6-keto-PGF1 alpha in the gastric mucosa was found in rats with bilateral nephrectomy before gastric lesions were seen. A higher mean ulcer area occurred in the forestomach and gastric mucosa 24-48 h after bilateral nephrectomy. We conclude, that the increased PGE2- and 6-keto-PGF1 alpha production by the gastric mucosa and forestomach was associated with the loss of normal renal tissue function. Despite the protection of PGE2 and PGI2 by gastric tissue, gastric lesions nevertheless occur in acute uraemic rats.

6-Ketoprostaglandin F1 alpha↗

Gastric mucosal PGE2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects.

PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia.

Adult↗

Gastric mucosal prostaglandin E2 levels in cirrhosis and portal hypertension.

Prostaglandin E2 (PGE2) tissue levels were measured, using radioimmunoassay, in specimens from the gastric antral mucosa in (a) healthy subjects, (b) patients without liver diseases in the absence or presence of gastric ulcers, and (c) patients with alcoholic cirrhosis in the absence or presence of gastric ulcers. These groups were divided further into subgroups with or without portal hypertension. PGE2 tissue levels in subjects without liver diseases were not significantly different from those of cirrhotic patients without portal hypertension. However, in cirrhotic patients with portal hypertension, the PGE2 content was significantly lower, especially in the presence of congestion in the mucosa (about 70-80%). When a gastric antral ulcer was present, a further statistically significant decrease of the PGE2 levels was observed. It was concluded that a decrease in the PGE2 tissue levels in the gastric mucosa of cirrhotic patients is related to the presence of portal hypertension. Congestion in the mucosa, as a pathogenetically relevant factor for mucosal PGE2 deficiency, may play a role.

Adult↗

Gastric mucosal prostaglandin E2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal disease, and in healthy subjects.

Investigations were carried out as to whether a disturbance in the formation of cytoprotective prostaglandin (PG) E2 in gastric mucosa is implicated in chronic renal failure. PGE2-like immunoactivity in gastric mucosal specimens was measured in individuals with chronic renal failure (creatine clearance less than 10 ml/min), in individuals without any renal disease, presenting either gastric ulceration or not, as well as in healthy subjects. Regardless of the group of patients, compared to normal mucosa a significant decrease in PGE2-like immunoactivity (about 50-70%) was found in mucosa from atrophic gastritis but not from superficial gastritis. Whenever patients of the control group or patients with kidney disease suffered from ulcers, PGE2-like immunoactivity showed a decrease of about 60-70% in the non-ulcerated mucosa compared to that of non-ulcer subjects. Moreover, ulcer patients showed the same frequency of gastritis and similar mucosal PGE2-like immunoactivity in their non-ulcerated mucosa. Furthermore, compared to the tissue from the ulcer edge, independent of the presence of renal disease, a relative deficiency of PGE2-like immunoactivity of about 50-60% was detected in the non-ulcerated mucosa of ulcer patients. We therefore conclude that chronic renal failure probably has no impact on PGE2 formation in the gastric mucosa. All told, relative mucosal PGE2 deficiency in gastric ulcer disease seems not to be correlated with chronic renal failure.

Adult↗