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Biomedical subjects

Matthias Schneider

Publications and source records attributed to Matthias Schneider.

At least 19 recordsLinked to original sources
PubMed2007

The effects of second-hand smoke on biological processes important in atherogenesis.

BACKGROUND: Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. METHODS: To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB100 was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation. RESULTS: "Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein-1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice. CONCLUSION: Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks.

Adiponectin↗
PubMed2006

Open versus closed treatment of fractures of the mandibular condylar process-a prospective randomized multi-centre study.

AIM: The aim of this international prospective randomized multi-centre study was to compare operative and conservative treatment of displaced condylar fractures of the mandible. METHODS AND PATIENTS: Out of a total of 88 randomized patients from 7 centres, 66 patients with 79 fractures of the mandibular condylar process completed the study and were evaluated. All fractures were displaced, being either angulated between 10 degrees and 45 degrees or the ascending ramus was shortened by more than 2mm. The follow-up examinations 6 weeks and 6 months following treatment included evaluation of radiographic measurements, clinical, functional and subjective parameters including visual analogue scale for pain and the Mandibular Function Impairment Questionnaire index for dysfunction. RESULTS: Correct anatomical position of the fragments was achieved significantly more often in the operative group in contrast to the closed treatment group. Regarding mouth opening/lateral excursion/protrusion, significant (p=0.01) differences were observed between both groups (open 47/16/7mm versus closed 41/13/5mm). The visual analogue scoring revealed significant (p=0.03) differences with less pain in the operative treatment group (2.9 open versus 13.5 closed). The Mandibular Function Impairment Questionnaire index recorded a significant (p=0.001) difference with less pain and discomfort in the open treatment group (10.5 versus 2.4 points). CONCLUSION: Both treatment options for condylar fractures of the mandible yielded acceptable results. However, operative treatment, irrespective of the method of internal fixation used, was superior in all objective and subjective functional parameters.

Adult↗
PubMed2006

Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials.

OBJECTIVE: Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials. METHODS: Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria. RESULTS: Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status. CONCLUSION: RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.

Adalimumab↗
PubMed2006

Optimized synthesis of AMPA receptor antagonist ZK 187638 and neurobehavioral activity in a mouse model of neuronal ceroid lipofuscinosis.

Previous structure-activity relationship studies in the search for a potent, noncompetitive alpha-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist led to 2,3-dimethyl-6-phenyl-12H-[1,3]dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine (ZK 187638). However, the first synthesis had some drawbacks regarding reagents, processes, and overall yield, which furthermore decreased when the synthesis was scaled up. Therefore, we now report a new synthetic route for this compound which requires fewer steps and is suited for large-scale production. This compound significantly relieved the symptoms of neuromuscular deficit in mnd mice, a model of neuronal ceroid lipofuscinosis with motor neuron dysfunction. After oral administration, the concentrations of the compound in the brain and spinal cord were about threefold higher than those in the plasma. In summary, this novel AMPA antagonist is accessible through an optimized synthetic route, has good neurobehavioral activity, oral bioavailability, and favorable brain penetration. This opens new possibilities for the treatment of devastating neurological diseases that are mediated by the AMPA receptor.

Administration, Oral↗
PubMed2006

[Secondary midfacial reconstruction using different surgical techniques and computer assisted surgery].

AIM: Aim of this retrospective study was to assess the outcome after secondary midfacial reconstruction using different operation techniques and computer assisted surgery. Functional and aesthetic aspects as well as experiences are reported. PATIENTS AND METHODS: 18 patients were assessed for enophthalmos, diplopia, and aesthetics during a follow-up period of up to 2.5 years. RESULTS: In 40% of the patients several techniques for soft and hard tissue reconstruction were used. In 5 of the 9 patients diplopia was improved; in 4 patients there was no change. A significant enophthalmos was corrected in 8 out of 12 patients. After additional surgery 6 patients had a good aesthetic result, 7 a satisfactory and 5 a poor. CONCLUSION: For secondary midfacial reconstruction often a combination of different surgical techniques is necessary. Bony asymmetries and enophthalmos were successfully corrected, however, functional and aesthetic impairment due to bad soft tissue condition are difficult to correct. Computer assisted surgery is helpful for dissection within the orbit, for graft placement, and for positioning of osteotomized segments.

Adolescent↗
PubMed2006

Efficacy of computer-assited surgery in secondary orbital reconstruction.

PURPOSE: In this study the efficacy of computer-assisted surgery (CAS) used for secondary orbital reconstruction after midfacial fractures was evaluated, comparing the clinical outcome with that after conventional surgery (CS). Special consideration was given to whether CAS can reduce the number of secondary corrections. PATIENTS AND METHODS: Twenty consecutive patients (24 orbits; 12 in each group) were assessed for enophthalmos, diplopia, and aesthetics during a follow-up period of up to 3 years. RESULTS: After CAS, enophthalmos was fully corrected in 8 of 11 orbits but after CS in only 6 of 10 orbits. Improvement of diplopia was achieved in 1 of 7 (CAS) and in 3 of 4 (CS) patients. The aesthetic result after secondary reconstruction and additional surgery was better in the CAS group. Additional surgery to correct bony structures was only necessary in 3 patients of the CS group. Additional soft tissue surgery was necessary in both groups. CONCLUSION: CAS can improve the clinical outcome of reconstructive bone surgery reducing the amount of additional hard tissue procedures. It was helpful during dissection of the scarred orbital tissue and placement of a graft. However, it had no impact on soft tissue correction especially with respect to function.

Adolescent↗
PubMed2006

Minimally invasive fracture treatment with cannulated lag screws in intracapsular fractures of the condyle.

PURPOSE: We examined the use of cannulated lag screw osteosynthesis for the treatment of fractures of the mandibular condylar head in providing a high-quality durable fixation, while at the same time reducing the trauma necessary for an open approach to the fracture site. PATIENTS AND METHODS: A preauricular approach was used for exposure, reduction, and osteosynthesis in 5 cases of type B condylar fractures. A cannulated screw system was used that allowed optimum placement of the self-cutting cannulated lag screw following insertion of a guiding wire and using clinical control to ensure its correct position. The joints were submitted to functional exercises immediately following surgery and postoperative radiologic, axiographic, and clinical follow-ups were performed. RESULTS: Radiologic follow-up revealed correct reduction and fixation in all 5 cases. Axiographic and clinical follow-up showed an initial limitation, but normal mobility of the condyles was achieved within 3 months postoperatively, with a maximum mouth opening of 41.2 +/- 9.4 mm after 6 months. There were no occlusal disturbances, no trismus, no lateral deviations of the mandible, and no nerve lesions. Intraoperatively, the method applied shortened the time necessary for and simplified the procedure of reduction and osteosynthesis. CONCLUSION: By using a cannulated lag screw, it was shown that the major factor in the extent of the trauma relating to surgical access was the reduction of the fracture fragments. The method ensured stable fixation of the fracture with a minimum of osteosynthesis material, while reducing the operative time. In combination with intraoperative imaging techniques it can also successfully be applied to other fractures in maxillofacial surgery.

Biomechanical Phenomena↗
PubMed2006

Change of mRNA amount of myosin heavy chain in masseter muscle after orthognathic surgery of patients with malocclusion.

INTRODUCTION: Surgical correction of malocclusion changes the force to moment ratio of masticatory muscles inserting at the mandible caused by shortening, lengthening and rotation of the bone following osteotomy. During muscle adaptation the expression of mRNA for the myosin heavy chain (MyHC) of type I and type II fibres may be changed. MATERIAL AND METHODS: The adaptation of the masseter muscle was investigated at the mRNA level in 10 patients 6 months after orthognathic surgery in the mandible. The competitive polymerase chain reaction (cPCR) is a suitable method for quantification of MyHC mRNA. For application of this minimal invasive method an amount of 35 mg muscle tissue was sufficient. RESULTS: 6 month postoperatively there was a deficiency of about 87% of MyHC mRNA for fibre type I and II in both groups of patients. The deficiency in patients with mesial position of the mandible was higher but not significant different to patients with distal malocclusion. CONCLUSION: Patients should use the postoperative interval for training their masticatory muscles. This improves the stability of treatment result and prevents relapse.

Adult↗
PubMed2006

Painful rash and swelling of the limbs after recurrent infections in a teenager: polyarteritis nodosa.

UNLABELLED: Polyarteritis nodosa is a rare disease in childhood and adolescence that is difficult to diagnose clinically. We report on a 17-y-old girl presenting with a history of recurrent infections of the upper respiratory tract and conjunctivitis followed by a painful rash on the upper and lower extremities resembling erythema nodosum. The diagnosis of polyarteritis nodosa was proven by skin biopsy. Therapy with intravenous immunoglobulins failed, but with systemic steroids she responded promptly. CONCLUSION: Polyarteritis nodosa is a differential diagnosis in adolescents presenting with fever and an erythema nodosum-like rash.

Adolescent↗
PubMed2006

Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.

Arthritis, Psoriatic↗
PubMed2005

ErbB2 growth factor receptor, a marker for neuroendocrine cells?

BACKGROUND/AIMS: The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed. MATERIALS AND METHODS: Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed. RESULTS: Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland. CONCLUSIONS: ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.

Adolescent↗
PubMed2005

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab.

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 +/- 1.7 and that in the physician's global assessment was 4.4 +/- 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (+/- 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

Antibodies, Monoclonal↗
PubMed2005

High-level lipoprotein [a] expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein [a] but not in low density lipoproteins.

Efforts to elucidate the role of lipoprotein [a] (Lp[a]) in atherogenesis have been hampered by the lack of an animal model with high plasma Lp[a] levels. We produced two lines of transgenic mice expressing apolipoprotein [a] (apo[a]) in the liver and crossed them with mice expressing human apolipoprotein B-100 (apoB-100), generating two lines of Lp[a] mice. One had Lp[a] levels of approximately 700 mg/dl, well above the 30 mg/dl threshold associated with increased risk of atherosclerosis in humans; the other had levels of approximately 35 mg/dl. Most of the LDL in mice with high-level apo[a] expression was covalently bound to apo[a], but most of the LDL in the low-expressing line was free. Using an enzyme-linked sandwich assay with monoclonal antibody EO6, we found high levels of oxidized phospholipids in Lp[a] from high-expressing mice but not in LDL from low-expressing mice or in LDL from human apoB-100 transgenic mice (P <0.00001), even though all mice had similar plasma levels of human apoB-100. The increase in oxidized lipids specific to Lp[a] in high-level apo[a]-expressing mice suggests a mechanism by which increased circulating levels of Lp[a] could contribute to atherogenesis.

Animals↗
PubMed2005

Comparison of the predicted surgical results following virtual planning with those actually achieved following bimaxillary operation of dysgnathia.

AIM: To simulate the surgery of dysgnathia, several forms of computer software allowing two-dimensional 'virtual' planning are frequently used. However, in many cases it is not possible to transfer the virtual plan accurately to the surgical site. It is the purpose of this study to find the errors likely to occur when transferring the data. METHODS: In 22 bimaxillary osteotomies for dysgnathia, the results of preoperative planning were compared with the surgical outcomes. The programme WinCeph 4.19 (Compudent) was used for cephalometric analyses and simulation of the operations. RESULTS: Six major skeletal parameters were evaluated when comparing both the planned and the actual outcome, and the following results were recorded: Delta-SNA 1.53 degrees (+/-1.20), Delta-SNB 1.67 degrees (+/-1.29), Delta-ANB 1.62 degrees (+/-1.47), Delta-NL-NSL 3.9 degrees (+/-2.30), Delta-ML-NSL 3.6 degrees (+/-3.7) and Delta-ArGoMe 6.1 degrees (+/-4.6). CONCLUSION: It was anticipated that the most important differences between planned and surgical outcomes were found to be in the vertical changes. Planning and data transfer was comparatively accurate with regard to sagittal data. Apart from several mechanical methods for data transfer, systems using navigation are therefore being discussed and used increasingly. They ensure accurate data transfer to the surgical site.

Cephalometry↗
PubMed2005

Infections in patients with rheumatoid arthritis treated with biologic agents.

OBJECTIVE: To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment. METHODS: Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. RESULTS: Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls. CONCLUSION: Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.

Adalimumab↗
PubMed2005

GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways.

The epidermal growth factor receptor (EGFR) plays a key role in the regulation of important cellular processes under normal and pathophysiological conditions such as cancer. In human mammary carcinomas the EGFR is involved in regulating cell growth, survival, migration and metastasis and its activation correlates with the lack of response in hormone therapy. Here, we demonstrate in oestrogen receptor-positive and -negative human breast cancer cells and primary mammary epithelial cells a cross-communication between G protein-coupled receptors (GPCRs) and the EGFR. We present evidence that specific inhibition of ADAM15 or TACE blocks GPCR-induced and proHB-EGF-mediated EGFR tyrosine phosphorylation, downstream mitogenic signalling and cell migration. Notably, activation of the PI3K downstream mediator PKB/Akt by GPCR ligands involves the activity of sphingosine kinase (SPHK) and is independent of EGFR signal transactivation. We conclude that GPCR-induced chemotaxis of breast cancer cells is mediated by EGFR-dependent and -independent signalling pathways, with both parallel pathways having to act in concert to achieve a complete migratory response.

ADAM Proteins↗