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D Schäfer

Publications and source records attributed to D Schäfer.

At least 19 recordsLinked to original sources
PubMed2003

Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes.

Recent works have shown that mechanical loading can alter the metabolic activity of chondrocytes cultured in 3D scaffolds. In this study we determined whether the stage of development of engineered cartilaginous constructs (expanded adult human articular chondrocytes/Polyactive foams) regulates the effect of dynamic compression on glycosaminoglycan (GAG) metabolism. Construct maturation depended on the culture time (3-14 days) and the donor (4 individuals). When dynamic compression was subsequently applied for 3 days, changes in GAG synthesized, accumulated, and released were significantly positively correlated to the GAG content of the constructs prior to loading, and resulted in stimulation of GAG formation only in the most developed tissues. Conversely, none of these changes were correlated with the expression of collagen type II mRNA, indicating that the response of chondrocytes to dynamic compression does not depend directly upon the stage of cell differentiation, but rather on the extracellular matrix surrounding the cells.

Cartilage, Articular↗
PubMed2003

Development and validation of a bioreactor for physical stimulation of engineered cartilage.

A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer-controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072+/-0.051 microm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74+/-0.36% for samples of 1.60-3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).

Bioreactors↗
PubMed2002

[Early functional treatment of surgically managed Achilles tendon rupture].

40 acute traumatic ruptures of the Achilles tendon were evaluated in a prospective study after open repair using an early functional rehabilitation protocol. The age of the patients averaged 43 (23-64) years. The operation consisted of a Kessler suture and microadaptation of the tendon. A special boot was used for after treatment. The boot was used 9 (1-18) weeks and full weight bearing was reported after 7 (1-16) weeks. The sick leave time averaged 5.5 (0-18) weeks. After 1 year, length and ankle joint motion were restored. Outcome was assessed using a 100-point score described by Thermann. After 4 months it averaged 73.5 +/- 15.5 points and after 1 year 94.5 +/- 6.0 points. There were no perioperative complications. One rerupture occurred 6 weeks postoperatively and was operated successfully. The combination of surgical repair and early functional after treatment resulted in normal function after 1 year, but requires cooperation of the patient.

Achilles Tendon↗
PubMed2002

[Estimation of accident risk in obstructive sleep apnea syndrome (OSAS) by driving simulation].

Abstract. Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

Accidents, Traffic↗
PubMed2002

Frequency of the Amsterdam criteria in a regional German cohort of patients with colorectal cancer.

Estimates of the colon cancer burden associated with hereditary nonpolyposis colorectal cancer (HNPCC) vary from less than 1 % to more than 5 %. Amsterdam criteria fulfilled within a kindred (classic Amsterdam and Amsterdam II criteria) are widely used to identify patients prone to HNPCC. The present study was initiated to assess the frequency of the Amsterdam criteria within a regional German cohort of 207 patients with a history of colorectal cancer (CRC). Data on individual and family cancer histories were available in 154 patients (73 women, 81 men; mean age at diagnosis 62.4 +/- 13.3 years). A total of 843 first degree relatives have been identified within the kindreds of whom 121 had verified cancers. In 28 of 154 families (18 %), at least one first degree relative of the index patient had CRC. With respect to a typical family history, five kindreds (3.2 %) were likely to suffer from HNPCC on a clinical basis (4 kindreds met the classic Amsterdam criteria and one kindred the Amsterdam II criteria). Testing for microsatellite instability could additionally be performed in 4 of 5 patients who met the Amsterdam criteria and revealed DNA instability in 3 cases. Moreover, a missense mutation of MSH2 (Gly965Asp) was detected in one patient with microsatellite instability. Based on the classic Amsterdam and Amsterdam II criteria approximately 3 % of a regional German cohort of patients with CRC are likely to suffer from HNPCC. However, the final diagnosis of HNPCC can only be established by detection of pathogenic germline mutations within the DNA mismatch repair genes.

Adult↗
PubMed2002

[Aspirin sensitivity: long term follow-up after up to 3 years of adaptive desensitization using a maintenance dose of 100 mg of aspirin a day].

BACKGROUND: The full clinical picture of aspirin intolerance, Sampter's triad, is associated with nasal polyposis, clinical sensitivity to most non steroidal antiinflammatory drugs (NSAID) and intrinsic bronchial asthma. But the triad can be incomplete and nasal polyposis can be the first clinical symptom of aspirin sensitivity. Although the exact mechanisms of aspirin intolerance as well as those of desensitization remain obscure, an in vitro assay on eicosanoid metabolism has been proven to be helpful in diagnosis and treatment as it correlates well to the individual severity of clinical symptoms. METHODS: For this investigation 30 patients, who were undergoing adaptive desensitization for aspirin intolerance, were followed-up between 1 and 3 years. They received a maintenance dose of oral aspirin of only 100 mg a day after an initial application of higher doses. Their clinical course as well as their in vitro parameters of eicosanoid release were monitored throughout the individual observation period. RESULTS: Desensitization was successful in 25 of the 30 patients regarding the recurrence rate of nasal polyps, severity of bronchial asthma and sense of smell. There was a clear positive correlation between clinical and in vitro parameters. Discontinuing of aspirin therapy lead to worsening of clinical symptoms, regardless of the prior duration of treatment. CONCLUSIONS: This article reviews the role of the in vitro assay and presents a desensitization protocol that can be maintained as a long term treatment without adverse side effects. Results suggest that the recurrence rate of nasal polyps after surgical therapy can be reduced using this protocol, however, only long term treatment can secure a beneficial outcome over time.

Adolescent↗
PubMed2001

Bethesda guidelines: relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer.

BACKGROUND: Microsatellite instability is a hallmark of mismatch repair deficiency in hereditary nonpolyposis colorectal cancer and results from mutations in the mismatch repair genes MLH1 or MSH2 or from gene inactivation associated with DNA methylation. The Bethesda guidelines were established to identify patients with colorectal cancer who should be tested for microsatellite instability. OBJECTIVE: To assess the Bethesda guidelines for detection of microsatellite instability and to determine the role of MLH1 promoter methylation in colorectal cancer. DESIGN: Prospective cohort study. SETTING: Tertiary care referral center in Frankfurt, Germany. PATIENTS: 125 consecutive patients with colorectal cancer. MEASUREMENTS: Patients were assessed according to the Bethesda guidelines, and tumor specimens were analyzed for microsatellite instability. Patients with microsatellite instability were tested for MLH1 promoter methylation and MLH1 and MSH2 germline mutations. RESULTS: Microsatellite instability was detected in 17 of 58 patients who fulfilled and 5 of 67 patients who did not fulfill criteria of the Bethesda guidelines. In 11 of 17 patients with microsatellite instability who fulfilled Bethesda guidelines, an MLH1 (n = 3), MSH2 (n = 7), or combined MLH1 and MSH2 (n = 1) mutation was found. Among the patients with microsatellite instability who did not fulfill Bethesda guidelines, no mutations were observed; MLH1 promoter methylation was observed in 6 of 11 patients with an MLH1 or MSH2 mutation and 5 of 11 patients without an MLH1 or MSH2 mutation. CONCLUSIONS: The Bethesda guidelines are useful for selecting patients for microsatellite instability testing. MLH1 and MSH2 testing should be recommended in all patients with colorectal cancer and microsatellite instability who fulfill at least one Bethesda criterion. MLH1 promoter methylation may accompany rather than initiate carcinogenesis in patients with colorectal cancer who have mismatch repair gene defects.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Familial fatal fetal cardiomyopathy with isolated myocardial calcifications: a new syndrome?

We describe three male sib fetuses with isolated myocardial calcifications resulting in intrauterine fetal death (IUFD) as early as the second trimester. No evidence for an underlying mitochondrial cytopathy, dystrophinopathy or myopathy was found. There were no signs of inflammation or a metabolic disorder, and the mother had no prenatal exposure of teratogenic drugs. Furthermore, no mutation in the Barth syndrome gene (G4.5) could be detected. Because isolated calcification of the heart and IUFD are not typical of any previously described inherited cardiomyopathy, it may represent a new familial fetal cardiomyopathy.

Calcinosis↗
PubMed2001

Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro.

Adult human articular chondrocytes were expanded in a medium with 10% serum (CTR) or further supplemented with different mitogens (i.e., EGF, PDGFbb, FGF-2, TGF beta 1, or FGF-2/TGF beta 1). Cells were then induced to redifferentiate in 3D pellets using serum-supplemented medium (SSM), serum-free medium (SFM), or SFM supplemented with factors inducing differentiation of chondroprogenitor cells (i.e., TGF beta 1 and/or dexamethasone). All factors tested during expansion enhanced chondrocyte proliferation and dedifferentiation, as assessed by the mRNA ratios of collagen type II to type I (CII/CI) and aggrecan to versican (Agg/Ver), using real-time PCR. FGF-2/TGF beta 1-expanded chondrocytes displayed the lowest doubling times, CII/CI and Agg/Ver ratios, averaging, respectively, 50, 0.2 and 15% of CTR-expanded cells. Redifferentiation in pellets was more efficient in SFM than SSM only for EGF-, PDGFbb- or FGF-2-expanded chondrocytes. Upon supplementation of SFM with TGF beta and dexamethasone (SFM TD), CII/CI ratios decreased 4.4-fold for EGF- and PDGFbb-expanded chondrocytes, but increased 96-fold for FGF-2/TGF beta 1-expanded cells. Chondrocytes expanded with FGF-2/TGF beta 1 and redifferentiated in SFM TD expressed the largest mRNA amounts of CII and aggrecan and generated cartilaginous tissues with the highest accumulation of glycosaminoglycans and collagen type II. Our results provide evidence that growth factors during chondrocyte expansion not only influence cell proliferation and differentiation, but also the cell potential to redifferentiate and respond to regulatory molecules upon transfer into a 3D environment.

Adult↗
PubMed2001

Recording of subcutaneous glucose dynamics by a viscometric affinity sensor.

AIMS/HYPOTHESIS: To provide a nonenzymatic sensor for glucose monitoring in subcutaneous tissue. METHODS: A continuously working affinity sensor based on the glucose-dependent viscosity of a sensitive liquid containing dextran and concanavalin A has been designed by arranging a microdialysis probe, two flow-resisting capillaries and two pressure transducers in a linear flow system. It allows synchronous processing of the viscosity of the sensitive liquid at the standard glucose concentration and the glucose concentration to be measured. In preliminary human trials the sensor was implanted into the subcutaneous tissue of the forearm and its read-out was compared with capillary blood concentrations. RESULTS: In vitro, the viscometric sensor shows a linear and long-term stable dependence on the glucose concentration without detectable drift. At the applied flow rate of the sensitive liquid (about 5 microliters/h) the technical delay is 5 to 10 min. The read-out of the implanted sensor followed the dynamics of the capillary blood glucose concentrations with a time-shift of 10 to 15 min but showed a systematic error when based on precalibration with polymer-free glucose solutions. After appropriate in vivo calibration, the read-out was in good or acceptable coincidence with capillary blood concentrations according to the error grid method and did not show any detectable reduction of sensitivity during the periods of measurement (up to 44 h). CONCLUSION/INTERPRETION: The viscometric-affinity sensor is an efficient tool for current research on glucose monitoring in the subcutaneous tissue and can potentially be further developed for routine clinical use.

Blood Glucose↗
PubMed2001

Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.

Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and viewed in slow motion to count the frequency. PGE2 led to a dose-dependent increase in CBF. This became significant at concentrations of 10(-10) and 10(-5) M (P < 0.01) but not at 10(-13) M (P > 0.05). Addition of cAMP (10(-10) to 10(-5) M) caused a significant (P < 0.01) increase in CBF, whereas depletion of endogenous cAMP after pre-incubation with the adenylate cyclase activator forskolin (10(-5) M) prevented the PGE2-induced increase in CBF (P > 0.05). The ciliostimulatory effect of PGE2 depends on an intact functioning of adenylate cyclase. These results point out that cAMP is directly implicated in the signal transduction pathway of PGE2-induced stimulation of CBF in cultured human ciliated cells of the nasal mucosa.

Adult↗
PubMed2001

Breathing and locomotion in patients with Parkinson's disease.

The phase relationship between respiration and locomotion was examined in ten patients with Parkinson's disease (PD, mean age 65, range 51-79 years) and in six healthy subjects (mean age 63, range 58-68 years). Locomotion was measured by means of pressure sensors attached below the subjects' feet. Respiration was measured using respiratory inductive plethysmography. The data were recorded with a battery-driven portable device. We determined the coordination degree as the portion of steps which occurred within 12/50 bins of the respiratory cycle. The mean degree of coordination of PD patients was 45.0%+/-11.9%, for the healthy subjects 85.1%+/-10.8% (P<0.001). Three healthy subjects showed a 2:1 ratio between step and breathing rate, three a 3:2 ratio. Two PD patients showed a coordination of 4:1 and 3:1, respectively, with a larger scatter than in controls. In the other eight patients steps were almost equally distributed over the entire respiratory cycle. We conclude that in patients with PD the coordination between locomotion and breathing is reduced.

Aged↗
PubMed2001

Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints.

OBJECTIVE: To quantify the expression of genes encoding extracellular matrix (ECM) proteins in human cartilage from normal and osteoarthritic (OA) joints. DESIGN: Human cartilage samples were classified as control (CTR) or OA according to clinical evaluation and assessed histologically and biochemically to confirm the diagnosis. mRNAs encoding collagen types I, II and X, aggrecan, versican, osteopontin and osteocalcin were quantified by real-time reverse transcription-PCR assays and normalized to a reference mRNA (GAPDH). RESULTS: RNA from native cartilage could be reproducibly and efficiently amplified by real-time PCR only if isolated using purification membranes. Primers and fluorescent probes for real-time PCR, endowed with comparable (<6% difference from GAPDH) and high (>91%) amplification efficiencies, were designed and validated for the selected ECM genes. The expression of most genes under investigation displayed large variations and was not significantly different in CTR and OA cartilage. Only osteopontin mRNA levels were significantly higher in OA than CTR specimens. mRNA ratios of collagen type II to I and of aggrecan to versican, defined as indexes of chondrocyte differentiation, were less variable within each population than the single genes and markedly higher (27.0 and 7.6-fold, respectively) in CTR than OA cartilage, with high statistical significance (P = 0.00013 and P = 0.00007, respectively). CONCLUSIONS: Our results provide evidence that gene patterns related to chondrocyte differentiation discriminate between CTR and OA human cartilage with higher sensitivity than single ECM genes. The method described here has the potential to improve understanding of the progression of OA and could become a valuable diagnostic tool.

Adult↗
PubMed2001

Design concept for diffractive elements shaping partially coherent laser beams.

A new two-step design algorithm for the calculation of a diffractive phase element (DPE) for use with partially coherent laser beams is presented. The optical reconstruction of the DPE is modeled by the convolution of a coherent diffraction pattern and the far-field intensity distribution of a partially coherent laser beam. Numerical deconvolution is applied to derive a suitable amplitude pattern as signal input to a standard iterative Fourier transform algorithm (IFTA). Theory and numerical results are presented. Compared with a single-step IFTA design, this new approach yields nearly equal diffraction efficiencies and a relative improvement of 15% in signal reconstruction error.

Journal Article↗
PubMed2000

Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS).

Wolf-Hirschhorn Syndrome (WHS) is caused by distal deletion of the short arm of chromosome 4 and is characterized by growth deficiency, mental retardation, a distinctive, 'greek-helmet' facial appearance, microcephaly, ear lobe anomalies, and sacral dimples. We report a family with a balanced chromosomal translocation 4;18(p15.32;p11.21) in the father and an unbalanced translocation resulting in partial monosomy 4 and partial trisomy 18 in one living boy and a prenatally diagnosed male fetus. Both showed abnormalities consistent with WHS and had in addition aplasia of one umbilical artery. Karyotyping of another stillborn fetus revealed a supernumerary derivative chromosome der(18)t(4;18)(p15.32;p11.21) of paternal origin and two normal chromosomes 4. The umbilical cord had three normal vessels. A third stillborn fetus with the same balanced translocation as the father had a single umbilical artery and hygroma colli.

Abnormalities, Multiple↗
PubMed2000

Effects of parkinsonian medication on sleep.

Patients suffering from Parkinson's disease (PD) often report about sleep disorders and excessive daytime sleepiness. To some extent, motor disabilities or neural degeneration of sleep modulating structures may be responsible for these effects. Depressive disorders also contribute to the occurrence of insomnia and daytime sleepiness. Nevertheless, dopaminergic, anticholinergic, and other drugs used in PD have a great impact on sleep/wakefulness mechanisms. They may indirectly improve or worsen sleep by changing motor symptoms such as akinesia, hyperkinesia, or tremor. Although their is only little information on the complex regulation of vigilance, it is well known that monoaminergic and cholinergic drugs could influence it directly. Data from animal experiments and clinical experiences led to the hypothesis of a biphasic influence on sleep by dopaminergic substances: small doses of L-Dopa e. g. appear to improve sleep whilst higher doses led to insomnia. Different dopaminergic receptor types or changes in receptor sensitivity may explain these phenomena. Dopaminergic and anticholinergic drugs suppress REM sleep. Recently, initial data on 'sleep attacks' after pramipexole or ropinirole treatment were published. Our preliminary results using 24 h polygraphic recordings showed excessive daytime sleepiness in patients taking ropinirole and L-Dopa which disappeared when changed to ropinirole monotherapy. Sleepiness did never appear as an irresistible attack. Current hypotheses on this topic are reviewed.

Adamantane↗
PubMed2000

Total hip arthroplasty after arthrodesis of the hip joint.

The results of 15 conversions of a hip arthrodesis into a total hip arthroplasty performed in the years 1980-1995 are reported. Fifteen patients (8 men, 7 women) underwent total hip arthroplasty 30.9 (range 2-61) years after spontaneous or operative fusion of a hip joint. The primary indications of the conversion were low-back pain (n = 10), knee pain (n = 2) and hip problems (n = 3). At follow-up examination 5.4 (range 2-13.3) years postoperatively, the Harris Hip Score averaged 86.0 (range 70.1-99.0). Six patients were pain-free, 7 had less pain, 2 felt no improvement of pain. All patients confirmed that they would undergo the operation again. The Trendelenburg sign was negative or mild in 8 patients and moderate to severe in 7. Aseptic loosening of 2 stems (1 cemented, 1 cementless) and 2 deep infections required revision surgery. We conclude that this operation can lead to satisfactory results even after a long duration of the arthrodesis. However, full function with no pain and a negative Trendelenburg sign could be obtained in only 20% (3/15) of the cases.

Adult↗