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Biomedical subjects

M Schneider

Publications and source records attributed to M Schneider.

At least 109 records · Page 6Linked to original sources

[Sensitivity and significance of nuclear magnetic tomography findings of finger joints in rheumatoid arthritis].

Evaluation of the sensitivity and value of magnetic resonance imaging (MRI) findings and miniarthroscopic investigations (mini-/needle-arthroscopy = MA) of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA). 30 patients with RA (21 female, 9 male), disease duration 2 months to 22 years and mean disease activity score (DAS) of 3.90 (range: 2.00-7.67) were examined by MRI of the hand (MCP region) and following MA of the MCP-II joints. MRI parameters for arthritis (synovial enhancement, synovial extension, cortical alterations, joint gap width) and corresponding macroscopic items (synovial extension, synovial hyperemia and vascularity, cortical alterations) by MA, scored semiquantitatively for synovitis (graduated from 0-III degree), were correlated. Additionally, normal radiographs of the hands were performed and compared with MRI findings concerning the detection of bony lesions. Evaluation of the 30 MRI and MA examination revealed highly significant correlations (p < 0.0001) for the parameters of synovial extension (MRI/MA), cortical alterations (MRI/MA) and synovial enhancement (MRI) compared to synovial hyperemia and vascularity (MA). We found significant correlations for parameters of activity and chronicity of RA pathology as assessed by MRI and MA. The detection rate of cortical lesions by MRI was two and a half times higher than by X-ray. MRI findings of MCP-II joints compared to those of MCP III-V showed that the MCP-II joint was more strongly involved.

Adult↗

[Synovial membrane diagnostic assessment in rheumatoid arthritis].

Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disease. At the beginning of the disease, where, based on today's knowledge the therapeutic possibilities are largest, the diagnostic methods do not permit a differentiated estimation of the prognosis. Conventional x-rays are mostly normal and serum markers unspecific. So far--in contrast to other diseases--only little information had been drawn from the pathomorphologic substrate "synovialis" itself to assess the prognosis. Reasons therefor were found in difficulties in obtaining synovial tissue besides surgical interventions, particularly in patients with early arthritis. By minimalizing the diagnostic instruments and improvement of the technique, synovial tissue sampling in RA has become minimally invasive and it is even possible to perform on the smallest joints, such as finger joints. Hereby, synovial analysis is open for detecting pathways of inflammation and joint destruction, which might support the advancement of new therapeutic strategies, followed by a better prognosis and outcome of RA.

Arthritis, Rheumatoid↗

Intolerance to neuroleptics and susceptibility for malignant hyperthermia in a patient with proximal myotonic myopathy (PROMM) and schizophrenia.

We report a patient with proximal myotonic myopathy who was treated with neuroleptics because of exacerbating schizophrenia. Under therapy with fluanxol, the patient developed muscle stiffness and oculogyric cramps. Treatment with both amisulpride and olanzapine lead to markedly elevated serum creatine kinase levels. An in-vitro contracture test was positive for halothane. Thus, in patients with all kinds of multisystemic myotonic myopathies, a susceptibility for malignant hyperthermia and intolerance towards neuroleptics should be taken into account.

Adult↗

Destructive osteoblastoma of the cervical spine with complete neurologic recovery.

STUDY DESIGN: Case report. OBJECTIVE: To describe a patient with a large tumor lesion of the 6th vertebrae affecting surrounding soft tissue, and symptoms of cord compression. Histologic diagnosis indicated a destructive osteoblastoma following dorsal and anterior resection and internal fixation. SETTING: University Hospital, Germany. METHODS: A 23-year old male patient was admitted with a 2-month history of increasing upper extremity weakness and pain. X-ray and MRI indicated massive involvement of the anterior and posterior elements of the 6th vertebrae with a large soft tissue mass. Following emergency decompression and dorsal stabilization, the pathologic investigation revealed a destructive osteoblastoma. Subsequent dorsal and anterior resection with internal fixation were performed. RESULTS: The patient initially presented with symptoms of beginning paraplegia of C6/7. According to the neurologic classification of spinal cord injury, motor function score was 56 and sensory function score 83. After emergency dorsal decompression and internal fixation with Luque-Instrumentation he showed increasing neurological recovery. Complete neurological recovery was achieved at 2 and 12-months postoperatively, following secondary dorsal and anterior resection of the tumor and internal fixation with bone cement (PalacosR) and Harms-cage. Radiologic signs of local recurrence were identified 1 year postoperatively. CONCLUSION: Osteoblastoma of the cervical spine is rare. Patients often present with severe neurological symptoms due to significant tumor mass. Complete resection is necessary to regain full recovery, to prevent recurrence and, in some cases, malignant transformation.

Adult↗

Up-regulation of the dendritic cell marker CD83 on polymorphonuclear neutrophils (PMN): divergent expression in acute bacterial infections and chronic inflammatory disease.

Upon cultivation with interferon-gamma (IFN-gamma ) and granulocyte/macrophage-colony stimulating factor (GM-CSF) polymorphonuclear neutrophils (PMN) acquire characteristics of dendritic cells, including expression of major histocompatibility complex (MHC) class II antigens, of the co-stimulatory antigens CD80, CD86 and of CD83, the latter considered to be specific for dendritic cells. Dendritic-like PMN were also able to present to T cells antigens in a MHC class II-restricted manner. To assess whether dendritic-like PMN are also generated in vivo, cells of patients with acute bacterial infections and of patients with chronic inflammatory diseases (primary vasculitis) were tested. During acute infection up to 80% of PMN acquired CD83, but remained negative for MHC class II, CD80 or CD86. PMN of patients with primary vasculitis expressed MHC class II antigens, CD80 and CD86, but not CD83, indicating that up-regulation of MHC class II and of CD83 are not necessarily linked to each other. Indeed, parallel studies with PMN of healthy donors showed that while IFN-gamma and granulocyte/macrophage colony stimulating factor (GM-CSF) induced both, MHC class II and CD83, tumour necrosis factor (TNF)-alpha selectively induced de novo synthesis of CD83. The function of CD83 on PMN is still elusive. A participation in the MHC class II-restricted antigen presentation could be ruled out, consistent with the segregation of MHC class II and CD83 expression. Regardless, however, of its function, CD83 expression could serve as a marker to differentiate between acute and chronic inflammation.

Acute Disease↗

Combination of microplate and miniplate for osteosynthesis of mandibular fractures: an experimental study.

Because of the limited space available in the mandible, especially in the mental foramen and apical region, miniature osteosynthesis material is desirable. Recently, metal deposition in the direct neighbourhood of osteosynthesis plates made of titanium or even in peripheral organs have been reported in the literature with increasing frequency. The size and amount of osteosynthesis material used should therefore be kept to a minimum. In an experimental study on 60 models, we examined load-carrying stability and in a second series, torsional strength of two-piece plastic models connected by either a single miniplate, two miniplates, or a titanium microplate plus a miniplate. In our test arrangement, the average loading capacity of the combination miniplate/miniplate was 470 N: that of the combination microplate/miniplate was only 267 N. The test group with the single miniplate had an average loading capacity of only 225 N. Masticatory loads on the plates exceeding 200 N occur only 3 months after osteosynthesis. At that time the fracture has largely consolidated. The torsional strength of the microplate/miniplate combination was similar to that of the miniplate/miniplate combination (1,000 Nmm resulting in a width of the gap measuring 0.8 mm and 0.5 mm, respectively). The single miniplate was considerably less stable (0.8 mm gap width as early as with 300 Nmm). According to Champy, rotational forces in the anterior region of the mandible amount to approximately 1,000 Nmm and need to be withstood by the osteosynthesis material. Our results suggest that treatment of fractures in the interforaminal region with a combination of microplate and miniplate will be stable enough for early mobilization.

Bone Plates↗

Cytogenetic analysis of giant oocytes and zygotes to assess their relevance for the development of digynic triploidy.

BACKGROUND: In order to assess the role of binucleate giant oocytes for generating digynic triploidy, we studied their frequency, maturation patterns and chromosomal complements at metaphase II (MII) or after fertilization. METHODS: Uncleaved, giant zygotes were incubated with podophyllotoxin and vinblastine, treated with hypotonic solution and fixed by a gradual fixation method. Giant MII oocytes were directly subjected to hypotonic treatment. The chromosomes were stained with Giemsa. RESULTS: A total of 7065 oocytes were collected during the study period, of which 18 (0.26%) were classified as giant cells. When considering only those patients in whom giant cells were identified (among other normal sized cells) a giant cell frequency of 18/237 (7.6%) was found. Nine cells underwent a union of the nuclei during maturation to MII and four of them became fertilized showing two pronuclei. Seven oocytes maintained the binucleate state to MII and one of them was fertilized showing three pronuclei. Ten unfertilized cells were available for cytogenetic analysis and proved to be diploid. All five giant zygotes revealed triploidy. CONCLUSIONS: The data suggest that giant oocytes may play an important, yet underestimated role in causing digynic triploidy. We recommend the exclusion of giant oocytes from IVF trials and that giant cells should be discarded, even if they carry the regular number of two pronuclei.

Adult↗

The cannabinoid agonist WIN 55,212-2 reduces sensorimotor gating and recognition memory in rats.

Cannabinoids can disrupt short-term memory in humans and animals and induce learning deficits and other cognitive impairments. In the present study we examined the role of a full cannabinoid agonist in short-term memory, sensorimotor gating, and the acquisition and expression of an operant learning paradigm in rats. We tested the effects of the synthetic cannabinoid WIN 55,212-2 (0.6 and 1.2 mg/kg) on short-term memory in social and object recognition tests, on prepulse inhibition (PPI) of startle, as well as on lever pressing for palatable food. Injections of 0.6 and 1.2 mg/kg WIN 55,212-2 impaired recognition memory and PPI in a dose-dependent manner, but had no effect on lever-pressing acquisition or expression, or on food preference. The PPI deficit was reversed by the administration of 0.1 mg/kg haloperidol. These data suggest that the synthetic cannabinoid WIN 55,212-2 does not lead to a general impairment of learning in an appetitive instrumental task, but significantly affects short-term memory and sensorimotor integration. The impairment in recognition and PPI might be due to deficits in attention-based short-term information processing.

Animals↗

Pharmacokinetics of marbofloxacin in horses.

Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.

Administration, Oral↗

Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity.

The polarized architecture of epithelial cells depends on the highly stereotypic distribution of cellular junctions and other membrane-associated protein complexes. In epithelial cells of the Drosophila embryo, three distinct domains subdivide the lateral plasma membrane. The most apical one comprises the subapical complex (SAC). It is followed by the zonula adherens (ZA) and, further basally, by the septate junction. A core component of the SAC is the transmembrane protein Crumbs, the cytoplasmic domain of which recruits the PDZ-protein Discs Lost into the complex. Cells lacking crumbs or the functionally related gene stardust fail to organize a continuous ZA and to maintain cell polarity. Here we show that stardust provides an essential component of the SAC. Stardust proteins colocalize with Crumbs and bind to the carboxy-terminal amino acids of its cytoplasmic tail. We introduce two different Stardust proteins here: one MAGUK protein, characterized by a PDZ domain, an SH3 domain and a guanylate kinase domain; and a second isoform comprising only the guanylate kinase domain. The Stardust proteins represent versatile candidates as structural and possibly regulatory constituents of the SAC, a crucial element in the control of epithelial cell polarity.

Amino Acid Sequence↗

Dinuclear titanium(IV) complexes from amino acid bridged dicatechol ligands: formation, structure, and conformational analysis.

Amino acid bridged dicatechol ligands 3a-e-H4 form dinuclear double-stranded coordination compounds [(3a-e)2Ti2(OCH3)2]2- with titanium(IV) ions. Due to the directionality of the ligands, the chirality of the strand, and the chiral complex units, up to seven isomers, I-VII, can be obtained for the double-stranded complexes of ligands 3a-e-H4. The composition of the mixture of isomeric compounds in solution is strongly dependent on the conditions of complex formation. Under thermodynamic control, only a few isomers are obtained, one of which is the major component of the mixture. X-ray structure analyses were performed for K2[(3b)2Ti2(OH)2] and K2[(3d)2Ti2(OH)2] (type I), and for the meso complex Na2[(3e)(3e')Ti2(OCH3)2]. A conformational analysis that uses Ramachandrans method revealed that the conformation of the amino acids in the ligand strands can be compared with those found for amino acids in helical peptide structures. The most favored isomer of [(3)2Ti2(OCH3)2]2- appears to be of type I, with the catecholamide unit located at the N terminus of the ligand strand that binds to a lambda-configurated titanium(IV) complex unit and the dihydroxybenzyl group at the C terminus that coordinates to a delta-configurated titanium(IV) complex unit. The lambda configuration at the N terminus induces the conformation of a right-handed helix in the amino acid residue, while the delta configuration induces the less favored left-handed helix.

Amino Acids↗

Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.

Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.

Adult↗

Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck.

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m(2)administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9-20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7-28.1 months; 95% CI: 3.9-7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B(12)supplementation.

Adult↗