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Biomedical subjects

T Krüger

Publications and source records attributed to T Krüger.

At least 19 recordsLinked to original sources

Release of vancomycin and teicoplanin from a plasticized and resorbable gelatin sponge: in vitro investigation of a new antibiotic delivery system with glycopeptides.

BACKGROUND: The aim of this study was to evaluate the efficacy of sustained release of vancomycin and teicoplanin from a resorbable gelatin glycerol sponge, in order to establish a new delivery system for local anti-infective therapy. MATERIALS AND METHODS: 60 plasticized glycerol gelatin sponges containing either 10 or 20% gelatin (w/v) were incubated in vancomycin or teicoplanin solution at 20 degrees C for either 1 or 24 h. In vitro release properties of the sponges were investigated over a period of 1 week by determining the levels of vancomycin and teicoplanin eluted in plasma using fluorescent polarization immunoassay. The rate constant and the half-life for the antibiotic release of each group were calculated by linear regression assuming first order kinetics. RESULTS: Presoaking for 24 h was associated with a significant increase in the total antibiotic release in all groups opposed to 1 h of incubation, except for the 10% sponges presoaked in teicoplanin. Doubling the gelatin content of the sponges from 10 to 20% significantly increased the total release of antibiotic load only in teicoplanin-containing sponges after 24 h incubation. In all corresponding groups investigated, release of vancomycin was more prolonged compared to teicoplanin, which allowed a gradual release beyond 5 days. The half-life (h +/- SEM) of both types of vancomycin-containing sponges was significantly prolonged by 24 h incubation in comparison to 1 h incubation (29.1 +/- 5.9 vs 5.9 +/- 1.0; p < 0.001, 30.0 +/- 2.1 vs 11.1 +/- 1.9; p < 0.001). However, neither doubling the gelatin content of the sponges nor a prolonged incubation was associated with a significantly prolonged delivery of teicoplanin. CONCLUSION: This study demonstrated a better diffusion-controlled release of vancomycin-impregnated glycerol gelatin sponges compared to those pretreated with teicoplanin. The plasticized glycerol gelatin sponge may be a promising carrier for the application of vancomycin to infected wounds for local anti-infective therapy.

Anti-Bacterial Agents↗

Microbial cell wall agents as an occupational hazard.

Organic dusts cause inflammatory reactions in the tissues exposed. The lung and the cells lining the surface of the respiratory tract are a primary target. Many receptors have been shown to react specifically on the presence of microorganisms that are ubiquitous elements in organic dusts. There is a great variability in the individual response to organic dusts. Almost 50% of Caucasians are hyporesponders to LPS exposure, and people with alpha-1-antitrypsin deficiency are hyperresponsive to organic dust exposure. The diseases resulting from organic dust exposures include asthma, allergy, hypersensitivity pneumonitis and toxic pneumonitis (organic dust toxic syndrome). This paper deals with inflammation and the subsequent mechanism of disease as it is encountered in industries with these exposures. Toxicological studies including human experimental exposures and ex vivo studies of cells are described. Cellular reactions are mediated through the attachment of, e.g. LPS and beta (1,3)-D-glucan to lipopolysaccharide binding protein, CD14 and Toll-like receptors. The relation between protein release and the gene activation is described. Furthermore, studies of the individual susceptibility will be reviewed.

Cell Wall↗

[Significance of lateral release in the therapy of patellar chondromalacia].

A retrospective study was performed in 26 patients who underwent an operation for femoro-patellar pain due to a patellar chondromalacia with or without minor patellar dislocation/lateral pressure syndrome. The average age of the patients was 28.5 (15-39) years. 22 of the 26 patients revealed minor chondral damages of the stages 1 and 2 according to Outerbridge. In 12 patients ("lavage" group), an arthroscopic joint debridement only was carried out, while an additional open, lateral retinaculum release was made in 14 patients ("lateral release" group). The patella's distance of dislocation according to Hepp was reduced on an average of 3.0 (0-7) mm (p = 0.0019). The results of Bentley's score obtained during the follow-up interval on an average of 30.1 (9 to 60) months were almost identical for both groups. "Good" and "very good" results were achieved in the "lavage" group (83.3 %) and "lateral release" group (78.6 % of the patients). Lateral release should be used in cases of patellar decentration between 5 and 10 mm and adequate pain symptoms. The post-operative distance of dislocation should be less than 5 mm. Under such conditions and with minor chondral damage, a combined approach by using an arthroscopic joint debridement and open lateral release is promising to treat a patellar dislocation/lateral pressure syndrome.

Adolescent↗

[Recurrence of Baker's cysts with regard to operation procedure and intraarticular pathology].

During the period from January 1990 to December 1998 65 patients were operated upon for a Baker's cyst. 41 patients (43 operations) were subjected to a clinical and sonographical follow-up examination and interrogation. In 11 cases, the cysts were merely removed, while an open synovectomy was carried out four times (rheumatics) in addition to the removal of the cysts, and arthroscopy with exstirpation was performed in 28 cases. The total recurrence rate was 14 % (6/43). Any significant differences between the groups were not found (p = 0.291). The overall complication rate was 18.6 %. In case of recurrence, the clinical results were significantly worse (p = 0.036). Apart from technical aspects of operation, the not quantifiable correlation between grade of chondromalacia and the formation of effusions following joint degeneration has to be discussed as a cause for recurrences. If both interventions are carried out in one course, there is no increased operative risk. Especially in cases with intraarticular pathological symptoms arthroscopy should precede each cyst exstirpation. With regard to the frequency of recurrence, the patients' expectation should be preoperatively objectified.

Adult↗

Lyapunov exponents and transport in the Zhang model of self-organized criticality.

We discuss the role played by Lyapunov exponents in the dynamics of Zhang's model of self-organized criticality. We show that a large part of the spectrum (the slowest modes) is associated with energy transport in the lattice. In particular, we give bounds on the first negative Lyapunov exponent in terms of the energy flux dissipated at the boundaries per unit of time. We then establish an explicit formula for the transport modes that appear as diffusion modes in a landscape where the metric is given by the density of active sites. We use a finite size scaling ansatz for the Lyapunov spectrum, and relate the scaling exponent to the scaling of quantities such as avalanche size, duration, density of active sites, etc.

Journal Article↗

[Surgery for pulmonary metastases--selection of patients and procedures].

Thirty percent of patients suffering from malignant disease develop pulmonary metastases. Effective chemotherapy is lacking for many of these tumors. A selected group of patients with metastases limited to the lung may benefit from pulmonary metastasectomy. This study describes the patient selection, the prognostic factors and the operative approach.

Disease-Free Survival↗

Results of arthroscopic joint debridement in different stages of chondromalacia of the knee joint.

A retrospective study was performed of 161 patients who had undergone arthroscopic operation for chondromalacia of the knee joint. After an average follow-up period of 40 (range 10-72) months, patients with severe articular cartilage lesions who had undergone articular lavage alone showed significantly poorer results (P < 0.001). With the same stage of chondromalacia and having undergone the same surgical procedure, younger patients showed better results than older patients. The more effective interruption of the circulus vitiosus during the development of degenerative joint diseases is the primary cause for better results achieved by mechanical debridement of the joint for patients suffering from grade 2 or higher. According to the literature, aggressive subchondral abrasion in severely degenerated knees does not show any benefits. Apparently, the success of the therapy depends to a great extent on the inferiority of the potential degenerative regenerate (lack of capacity of intrinsic regeneration of the hyaline cartilage) as well as on the grade and the progression of chondromalacia. Almost every second patient suffering from grade 4 chondromalacia complained of recurrent pain 1 year postoperatively. One of every 6 patients received a knee joint prosthesis within the 1st year. Therefore, the patients' preoperative expectations have to be clearly objectified. The surgical procedure as an operation with a low complication risk can also be justified as a temporary alternative to total knee arthroplasty in patients suffering from a high-grade degeneration of the joint.

Adult↗

Arthroscopy after dysfunctional total knee arthroplasty: two cases with peg fracture of the polyethylene insert.

Arthroscopy may be indicated in patients with painful dysfunction of the knee joint following total joint replacement. Arthrofibrosis, impacted soft tissue, patellar malalignment, synovialitis, and intra-articular foreign bodies can be treated with the promise of a good outcome. Two cases of peg fracture of the polyethylene insert of a semiconstrained knee prosthesis are presented. In relation to fracture position, instability and locking-up of the joint were clinically manifest. When arthroscopy is used judiciously, its merits are found in ensuring the proper diagnosis and in the reliable planning of treatment. When the patient reports locking-up of the joint, the rare complication of a polyethylene peg fracture must be considered.

Arthroplasty, Replacement, Knee↗

[The effect of arthroscopic joint debridement in advanced arthrosis of the knee joint].

A retrospective study was performed examining 84 patients who had undergone arthroscopic debridement for high-grade osteoarthritis of the knee joint. After an average follow-up period of 52 (35-72) months only 14 (16.7%) patients indicated an improvement of the preoperative situation. 36 (42.8%) patients had severe joint pain after one year postoperatively. 17 (24.3%) patients were evaluated with 85-100 points and 53 (75.7%) patients with less than 85 points in a modified Lysholm-score. There were better results in younger patients (< 50 years). Compared with the literature, aggressive subchondral abrasion does not show any benefits. Patients' preoperative expectations have to be clearly objectified. With this prerequisite the surgical procedure as an operation with low complication risk can also be justified as a temporary alternative to total knee arthroplasty in patients suffering from a high-grade degeneration of the knee joint.

Adult↗

Guanylyl cyclases with the topology of mammalian adenylyl cyclases and an N-terminal P-type ATPase-like domain in Paramecium, Tetrahymena and Plasmodium.

We cloned a guanylyl cyclase of 280 kDa from the ciliate Paramecium which has an N-terminus similar to that of a P-type ATPase and a C-terminus with a topology identical to mammalian adenylyl cyclases. Respective signature sequence motifs are conserved in both domains. The cytosolic catalytic C1a and C2a segments of the cyclase are inverted. Genes coding for topologically identical proteins with substantial sequence similarities have been cloned from Tetrahymena and were detected in sequences from Plasmodium deposited by the Malaria Genome Project. After 99 point mutations to convert the Paramecium TAA/TAG-Gln triplets to CAA/CAG, together with partial gene synthesis, the gene from Paramecium was heterologously expressed. In Sf9 cells, the holoenzyme is proteolytically processed into the two domains. Immunocytochemistry demonstrates expression of the protein in Paramecium and localizes it to cell surface membranes. The data provide a novel structural link between class III adenylyl and guanylyl cyclases and imply that the protozoan guanylyl cyclases evolved from an ancestral adenylyl cyclase independently of the mammalian guanylyl cyclase isoforms. Further, signal transmission in Ciliophora (Paramecium, Tetrahymena) and in the most important endoparasitic phylum Apicomplexa (Plasmodium) is, quite unexpectedly, closely related.

Amino Acid Sequence↗

[Results of the Elmslie-Trillat procedure in cases of patella(sub)luxation related to chondral pathology].

Between May 1981 and December 1993, 120 patients (126 knee joints) were operated using the Elsmlie-Trillat procedure because of patella(sub)luxation. 79 patients were reviewed at an average follow up of 4.1 (1-13.6) years. 46 women and 33 men were operated with an average age at operation of 26.9 (14-59) years. The examination included Bentley's Score, radiological parameters (e. g. grading of patella dislocation), grading of chondromalacia and patient characteristics (e. g. age, pre-operative time). 64 knee joints (70. 3 %) were evaluated 'very good' and 'good', using the score of Bentley. There were significantly worse results in cases with higher grading of chondromalacia (p <0.0036), longer pre-operative time (p < 0.012) and older patients (p < 0.0023). The worst and most highly significant results were in these patients with prior knee surgery (p < 0.0001). A good patella relocation correlated with improved results (p < 0.001). There was no difference in cases with patella dislocation and/or patellasubluxation. In conclusion, the Elmslie-Trillat procedure should be carried out 'in the correct manner and at an early stage'. To optimise the therapy in cases of patella dislocation the high number of operation techniques should be analysed and used regarding risk groups.

Adolescent↗

Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain.

The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Although a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the patophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostriatum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine.

Animals↗

Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.

The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) values of 0.81 +/- 0.5 and 0.87 +/- 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value of 85 +/- 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.

Animals↗

Subconscious detection of threat as reflected by an enhanced response bias.

Neurobiological and cognitive models of unconscious information processing suggest that subconscious threat detection can lead to cognitive misinterpretations and false alarms, while conscious processing is assumed to be perceptually and conceptually accurate and unambiguous. Furthermore, clinical theories suggest that pathological anxiety results from a crude preattentive warning system predominating over more sophisticated and controlled modes of processing. We investigated the hypothesis that subconscious detection of threat in a cognitive task is reflected by enhanced "false signal" detection rather than by selectively enhanced discrimination of threat items in 30 patients with panic disorder and 30 healthy controls. We presented a tachistoscopic word-nonword discrimination task and a subsequent recognition task and analyzed the data by means of process-dissociation procedures. In line with our expectations, subjects of both groups showed more false signal detection to threat than to neutral stimuli as indicated by an enhanced response bias, whereas indices of discriminative sensitivity did not show this effect. In addition, patients with panic disorder showed a generally enhanced response bias in comparison to healthy controls. They also seemed to have processed the stimuli less elaborately and less differentially. Results are consistent with the assumption that subconscious threat detection can lead to misrepresentations of stimulus significance and that pathological anxiety is characterized by a hyperactive preattentive alarm system that is insufficiently controlled by higher cognitive processes.

Adult↗

Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men.

Data regarding the neuroendocrine response pattern to sexual arousal and orgasm in man are inconsistent. In this study, ten healthy male volunteers were continuously monitored for their cardiovascular and neuroendocrine response to sexual arousal and orgasm. Blood was continuously drawn before, during and after masturbation-induced orgasm and analyzed for plasma concentrations of adrenaline, noradrenaline, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, growth hormone (GH), beta-endorphin and testosterone. Orgasm induced transient increases in heart rate, blood pressure and noradrenaline plasma levels. Prolactin plasma levels increased during orgasm and remained elevated 30 min after orgasm. In contrast, none of the other endocrine variables were significantly affected by sexual arousal and orgasm.

Adult↗

[Possibilities of follow-up imaging after implantation of a carbon fiber-reinforced hip prosthesis].

INTRODUCTION: There are many problems in the radiological diagnosis of aseptic loosening in total hip arthroplasty. Computed tomography (CT) and magnetic resonance tomography (MRT) are not usable for metallic implants (stainless steel, cobalt alloy, titanium alloy). MATERIAL AND METHODS: From April 1993 to December 1993 15 CFRP non-cemented hip prostheses have been implanted. In a prospective clinical study plane radiographs, CT and MRT have been analysed. RESULTS: Three stems were revised (1 femoral fracture, 1 severe thigh pain, 1 aseptic loosening). CFRP are not visible in plane radiographs. There was a complete (two-third of the cases) or nearly complete (one-third of the cases) small sclerotic interface between the prosthesis and the bone, these were apparent in CT and MRT in stable implant cases and did not have any clinical correlations. DISCUSSION: The small sclerotic interface is quite different in comparison to so called "Reactive Lines". In one case of aseptic loosening there was an interposition of soft tissue between prosthesis and bone in MRT and CT. CFRP inaugurates new diagnostic possibilities in aseptic loosening of hip prosthesis and in tumour surgery too.

Aged↗

Characterization of the interaction between the restriction endonuclease McrBC from E. coli and its cofactor GTP.

McrBC, a GTP-dependent restriction enzyme from E. coli K-12, cleaves DNA containing methylated cytosine residues 40 to 80 residues apart and 3'-adjacent to a purine residue (PumCN40-80PumC). The presence of the three consensus sequences characteristic for guanine nucleotide binding proteins in one of the two subunits of McrBC suggests that this subunit is responsible for GTP binding and hydrolysis. We show here that (i) McrB binds GTP with an affinity of 10(6) M-1 and that GTP binding stabilizes McrB against thermal denaturation. (ii) McrB binds GDP about 50-fold and ATP at least three orders of magnitude more weakly than GTP. (iii) McrB hydrolyzes GTP in the presence of Mg2+ with a steady-state rate of approximately 0.5 min-1. (iv) McrC stimulates GTP hydrolysis 30-fold, but substrate DNA has no detectable effect on the GTPase activity of McrB, neither by itself nor in the presence of McrC. (v) Substitution of N339 and N376 with alanine allowed us to identify NTAD (339 to 342) rather than NKKA (376 to 379) as the equivalent of the third consensus sequence motif characteristic for guanine nucleotide binding proteins, NKXD.

Adenosine Triphosphate↗

The recognition of methylated DNA by the GTP-dependent restriction endonuclease McrBC resides in the N-terminal domain of McrB.

McrBC is a GTP-dependent restriction endonuclease of E. coli K12, selectively directed against DNA containing modified cytosine residues. McrB, one of its components, is responsible for the binding and, together with McrC, for the cleavage of DNAs containing two 5'-Pu(m)C sites separated by 40-80 base pairs. Gel retardation assays with wild-type and mutant McrB reveal that (i) single 5'-Pu(m)C sites in DNA can be sufficient to elicite binding by McrB. Binding to such substrates is, however, weak and strongly dependent on the sequence context of Pu(m)C sites. (ii) Strong DNA binding (K(ass) approximately 10(7)M[-1]) is dependent on the presence of at least two Pu(m)C sites, even if they are separated by less than 40 bp, and is modulated by the sequence context (-A(m)CCGGT- --> -A(m)CT(C/G)AGT- --> -AGG(m)CCT- --> -AAG(m)CTT-). (iii) DNA binding by McrB is accompanied by formation of distinct multiple complexes whose distribution is modulated by GTP. (iv) McrC, which cannot bind DNA by itself, moderately stimulates the DNA binding of McrB and converts McrB-DNA complexes to large aggregates. (v) Deletion of the C-terminal half of McrB, which harbors the three consensus sequences characteristic for guanine nucleotide binding proteins, leads to protein inactive in GTP binding and/or hydrolysis and in McrC-assisted DNA cleavage; the protein, however, remains fully competent in DNA binding. (vi) Mutations in McrB which lead to a reduction in GTP binding and/or hydrolysis can affect DNA binding, suggesting that the two activities are coupled in the full-length protein.

Base Composition↗