Biomedical subjects

J Wiltfang

Publications and source records attributed to J Wiltfang.

At least 55 records · Page 3Linked to original sources

PubMed2003

Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes.

Large bone defects resulting from nonunion fractures or tumour resections are common clinical problems. Recent studies have shown bone morphogenetic protein-2 (BMP-2) gene transfer using adenoviral vectors to be a promising new therapeutic approach. However, comparative studies of different vectors are required to identify the optimal system for possible clinical trials. This study compares the use of liposome-mediated and adenoviral gene transfer for the generation of autologous BMP-2-producing bone marrow stromal cells (BMSC). Primary BMSC isolated from the rat femur were treated ex vivo with either an adenovirus or a liposome carrying human BMP-2 cDNA. The genetically modified cells were evaluated in vitro and transplanted into critical size defects in the rat mandible in vivo. BMSC treated with a reporter gene vector or untreated BMSC served as controls. The newly formed tissue was analysed by in situ hybridization, radiography and immunohistochemistry. Both groups of genetically modified cells produced BMP-2 for at least 2 weeks, and markers of new bone matrix such as osteopontin and osteocalcin were observed within 2 weeks following gene transfer. In the liposome group, the critical size defects were found completely healed at 6 weeks after the gene transfer, whereas the more efficient adenoviral gene transfer allowed for complete bone healing within 4 weeks. None of the three control groups showed bone healing, not even after 8 weeks. Thus, both liposome-mediated and adenoviral BMP-2 gene transfer to primary BMSC are suitable methods to achieve the healing of critical size bone defects in rats. As liposomes have proven sufficient for this purpose and offer several advantages over any other vector, such as ease of preparation, theoretically no limitation of the size of the DNA, and less immunological and safety problems, they may represent the best vector system for future clinical trials of bone regeneration by BMP-2 gene therapy.

Adenoviridae↗

PubMed2003

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias.

Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neuro-degenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.

Aged↗

PubMed2003

[Excitatory neurotransmission in alcoholism].

Glutamate is the neurotransmitter at the majority of excitatory synapses in the mammalian CNS. It has been proposed that neurotoxicity linked to chronic alcoholism is mediated primarily by activation of glutamate N-methyl-D-aspartate (NMDA) receptors. Since ethanol stabilizes the membrane potential of NMDA receptors a persistent attenuation of glutamatergic neurotransmission occurs in chronic alcoholism resulting in a compensatory up-regulation of NMDA receptors. Thus, delayed neurotoxicity can be triggered by rebound activation of NMDA receptor-mediated neurotransmission during the withdrawal state. Besides glutamate, homocysteine and excitatory amino acids (EAA) have been shown to act as endogenous agonists at the NMDA receptor and increase excitatory postsynaptic potentials. There is evidence that chronic alcoholism is associated with a derangement in this sulfur amino acid metabolism. These findings indicate the role of hyperhomocysteinemia for withdrawal symptoms, the withdrawal state, and alcoholism-associated brain atrophy. The role of alcoholism-associated hyperhomocysteinemia in respect to NMDA-receptor mediated neurotoxicity and excitotoxicity is discussed.

Alcoholism↗

PubMed2003

Sample preparation technique and white cell content influence the detectable levels of growth factors in platelet concentrates.

BACKGROUND AND OBJECTIVES: Autologous platelet concentrate (PC) is applied locally to improve wound healing and tissue repair. Previous measurements of the growth factor content of platelets have given conflicting results. To date, there is no information on the influence of different preanalytical sample-preparation methods on the detectable amount of growth factors. MATERIALS AND METHODS: We measured the level of growth factors in PCs obtained by plateletpheresis and by leukapheresis. We subjected aliquots of these components to six different preparation methods: freezing/thawing once or twice; dissolution in 0.5% Triton-X-100; and clot formation by the addition of calcium and thrombin with subsequent incubation for 1 h, for 24 h, or for 1 h followed by freezing and thawing. RESULTS: In samples dissolved in Triton-X-100, higher levels of growth factors were detected than in the other specimens. In comparison to clot formation, freezing and thawing platelets twice was equivalent with respect to the release of platelet-derived growth factor (PDGF) but superior with respect to the release of transforming growth factor-beta1 (TGF-beta1). Overall, mean levels of 4.77 x 10(-16) g of PDGF-AB, 2.2 x 10(-17) g of PDGF-BB, and 2.41 x 10(-16) g of TGF-beta1 were found per single human platelet in white blood cell (WBC)-poor samples dissolved in Triton-X-100. CONCLUSIONS: Dissolving PC in Triton-X-100 releases maximum quantities of growth factors from platelets. The release of each growth factor by any sample preparation method should be investigated and interpreted separately. The preanalytical sample-preparation method, as well as the platelet and WBC content, influence the measurable levels of growth factors in PCs. The results implicate the need to correct, considerably upwards, previous estimations of the PDGF content of platelets.

Adult↗

PubMed2003

Loss of 9p21 is embedded in a complex but consistent pattern of genomic imbalances in oral squamous cell carcinomas.

35 oral squamous cell carcinomas examined previously by comparative genomic hybridization (CGH) exhibited 5 up to 47 copy number alterations (CNAs). 13 of those cases showed a loss of parts of the short arm of chromosome 9, band p21 being affected in all of these cases. A highly complex but strikingly consistent pattern of genomic imbalances with an average 31.5 CNAs per tumor was associated with this deletion, and gains clearly dominated over losses of genomic material. Comparable patterns, however, could also be found in tumors with a high number of CNAs (24 CNAs) but without the deletion. Low numbers of imbalances were accompanied by low consistency of the CNA patterns. None of these latter cases showed the deletion 9p21. 66.7% of the dim(9p21)-positive tumors were of class pT4 (vs. 22% in dim(9p21)-negative cases), 77% of stage III or IV (vs. 47% in the group without the deletion), but only 8% of the dim(9p21)-positive tumors were classified as grade 3 (vs. 41% in the negative group). Other clinicopathologic features like prevalence of relapse, or survival time could not be as clearly associated with the deletion. For instance, short relapse-free survival was clearly associated with a high number of CNAs, rather independent of presence or absence of dim(9p21) in the affected tumor. From these findings it is concluded that previously found associations of 9p21 deletion with clinical parameters can reasonably be estimated only in the context of the pattern and complexity of the genomic imbalances accompanying this chromosomal loss in the examined tumors.

Adult↗

PubMed2002

Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease.

BACKGROUND: Diagnosis of Creutzfeldt-Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of tau-protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated. METHODS: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion protein type and polymorphism at codon 129. RESULTS: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for tau-protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion protein and methionine/valine or valine/valine polymorphism at codon 129, tau-protein has a higher diagnostic sensitivity than 14-3-3 protein. Tau-protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands. CONCLUSION: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the tau-protein ELISA. The advantage of the tau-protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable tau-protein levels. This increases information on 14-3-3-negative patients with CJD and especially on patients with other diseases.

14-3-3 Proteins↗

PubMed2002

Degradation characteristics of alpha and beta tri-calcium-phosphate (TCP) in minipigs.

In seven Goettingen minipigs 3.5--4.7-ml cancellous bone defects were created in the area of the tibial head on both sides. The defects were filled with alpha-TCP or beta-TCP (tricalciumphosphate). ITI implants (Straumann, Freiburg, Germany) of 3.2 x 12-mm length were inserted into the underlying ceramic substitutes. Two additional pigs were used as control. Within the periods of observation (4, 16, 20, 28, 46, 68, and 86 weeks) fluorescent dyes were applied. Nondecalcified thin-sliced sections were examined by means of light and fluorescence microscopy. In addition microangiography and microradiography were performed. Bony regeneration occurred basally and on the sides of the defect according the angiogenetic reossification pattern. Resorption was due to a hydrolytic and cellular degradation process. After 46 weeks histomorphological evaluation showed an incomplete osseointegration of the simultaneously implanted dental implants. The bone contact surface ratio was lower than 25%. After 86 weeks 95--97% of both alpha- and beta-TCP were resorbed. Ceramic residuals stayed within the newly formed trabeculae thus resisting further degradation until remodeling occurred. Both alpha- and beta-TCP show a comparable degradation process. At the 86-week postoperative point only small residuals of the ceramic can be found. These residuals stay within the newly formed trabeculae, which show a functional orientation. In comparison control defects showed only sparse reossification. The beta-TCP material shows an accelerated degradation mode and has an optimal reactivity with the surrounding tissues. According to the results of this animal experiment both materials can be classified as bone-rebuilding materials.

Animals↗

PubMed2002

[Osteosynthesis systems in mouth, jaw and facial surgery].

The introduction of stable osteosynthesis of mandibular fractures in the late 1960s for trauma patients meant an increase in quality of life. Intermaxillary immobilization and time in hospital could be reduced significantly. Later on, miniplates became popular in most trauma centers to treat mandibular fractures. Compared to the technique of stable osteosynthesis, miniplating is less demanding and the complication rates are similar. In midfacial fractures, too, miniplate osteosynthesis could guarantee three-dimensional stability. With the help of microplates even the smallest bony structures can be fixed following reduction. Degradable plates, which are available today, are used for craniofacial and midfacial indications; however, up to now degradable plates are not suitable for load-bearing areas.

Biomechanical Phenomena↗

PubMed2002

[Implantology in oromaxillofacial surgery].

Since the last 30 years endosseous implants are a well established treatment technique in maxillofacial surgery. Implants are used in the rehabilitation of patients having lost parts of maxilla or mandible due to tumor surgery, or which due to radiotherapy have problems tolerating mucosa-borne dentures. The implant borne prosthesis will aid to regain live quality to those patients. Improvement of live quality is also the result when epithetic reconstructions of soft tissue defects in the face are stabilized by extraoral implants. Aim of the paper is to give an overview on important implant related pathophysiological osseous healing patterns, discuss methods to influence these processes, to show correction possibilities for the bony bed and highlight their indications as well as to inform about clinical experiences with endosseous implants.

Dental Implantation, Endosseous↗

PubMed2002

[Evaluation of B-scan ultrasound, 3-D ultrasound, roentgen diagnosis and sinus endoscopy in follow-up assessment of the maxillary sinus after sinus floor elevation].

PROBLEM: The aim of this study was to determine which technique--B-scan sonography, 3D sonography, X-ray, or endoscopy--is the most effective for diagnosis in changes of the maxillary sinus after sinus lift and simultaneous augmentation. MATERIAL AND METHODS: In 33 patients the maxillary sinus was examined before sinus lift, 1 week and 6 months postoperatively with a 7.5-MHz linear scanner and 3D sonography. At the same time, the sonographic results were compared with the X-ray as well as the endoscopic results. Endoscopy of the maxillary sinus was only applied during the sinus lift operation and the abutment operation after 6 months. RESULTS: A total of 56 operations of sinus lift and simultaneous augmentation with autogenous bone were carried out. Preoperatively, there where no pathological findings detectable in the maxillary sinus. One week postoperatively, the X-rays as well as the sonographic images revealed thickening of the mucosa in 40 maxillary sinuses. After the healing period of 6 months, polyposa was still detected in three cases sonographically, in the radiographic follow-up as well as endoscopically. The sonographic 3D imaging of the maxillary sinus improved the spatial visualization of postoperative changes in the maxillary sinus and the reliability of the diagnosis. CONCLUSION: Due to the lack of radiation, the cost effectiveness, and its reproducibility, sonography is suitable as a primary screening technique in recall. In cases of normal sonographic findings but clinical symptoms, CT, MRT, and endoscopy should be performed to exclude pathological processes of the posterior maxillary sinus.

Alveolar Ridge Augmentation↗

PubMed2002

[Endoscopically-assisted LeFort I osteotomy in distraction procedures of the maxilla].

PURPOSE: The purpose of this study was to demonstrate the feasibility of combining a minimally invasive endoscopic approach to the maxilla with transverse and sagittal distraction procedures. MATERIALS AND METHODS: Four human cadavers were used for training of a minimally invasive access to the maxilla to perform an endoscopically assisted Le Fort I osteotomy, before this technique was applied in three patients with transverse and sagittal growth deficits of the maxilla. Access to the maxilla was gained through a small mucosa incision in the vestibule to create a visualization port to the maxillary sinus through a bur hole. Landmarks were identified through the endoscope before a Le Fort I osteotomy was performed using straight and angulated chisels of different form and angulation. In two patients, the maxilla was split sagittally to perform a transverse maxillary expansion. In one patient, a buried distractor was applied close to the piriform aperture to correct a sagittal growth deficit in a hypoplastic maxilla. RESULTS: The endoscopic exposure of the maxillary sinus walls from within the sinus, the accurate identification of landmarks, and the creation of a Le Fort I osteotomy was achieved in all cases. Distractor application close to the piriform aperture rendered good stability. CONCLUSION: The results of these case reports indicate that the endoscopic approach to the maxillary sinus allows excellent exposure of the sinus walls to perform an endoscopically assisted Le Fort I osteotomy. The combination of endoscopy and osteodistraction supports the trend toward minimally invasive, less traumatic surgical procedures, especially in individuals still growing.

Adolescent↗

PubMed2002

Soft tissue findings above submerged titanium implants--a histological and spectroscopic study.

The aim of this study was to check the titanium level within the muco-periosteal flaps covering submerged titanium implants. The investigated material included 38 biopsies taken after 2.4-18 months (mean: 5.9) after implant insertion. Due to the evident time delay between implantation and taking the biopsy any influence of the implantation trauma itself was excluded. The implants came from the following producers: HaTi (Matthys, Switzerland), ITI (Straumann, Switzerland) and Branemark (Nobelbiocare. Sweden). The surface areas of these implants differ in size and structure. A comparison between the titanium impregnation of the investigated biopsies did not demonstrate any remarkable influence of the surface differences. This can be explained by the fact that only the top diameter and not the implant surface as a whole was the contact area with the excised tissue. Titanium in the biopsies was analysed in terms of its effect histologically and regarding the titanium quantity by spectrophotometry. Even the highest titanium contamination was without a negative effect on the muco-periosteal cover flaps. A correlation between time delay between implantation and biopsy or of the titanium amount and tissue reactions was not demonstrable. In summary, the results again highlighted the biological acceptance of titanium.

Biocompatible Materials↗

PubMed2002

Long-term results of distraction osteogenesis of the maxilla and midface.

Since the beginning of 1998, eight patients have been treated by osteodistraction to correct hypoplasia of the maxilla and midface of various origins. Among them were five patients who were treated by high LeFort I osteotomies and insertion of subcutaneous intraoral distraction devices in the malar region. In the remaining three patients, extraoral distraction devices were applied after LeFort II and III osteotomies. Distraction osteogenesis was successful in all cases, resulting in a mean sagittal bone gain measured parallel to the skull base of 9.0 mm (range 4.5-12.0) in the group treated with intraoral distractors and a mean of 20.3 mm in the extraoral distraction group (range 15.0-25.0). All patients were kept under orthodontic supervision before, during, and after osteodistraction. Long-term cephalometric and clinical evaluation after a mean follow-up period of 24 months in the intraoral distraction group (range 22-26) and 12 months in the extraoral distraction group (range 10-14) show stable results concerning the skeletal and dental relations. Long-term follow-up is necessary.

Adolescent↗

PubMed2002

Specific 14-3-3 isoform detection and immunolocalization in prion diseases.

14-3-3 proteins are involved in signalling processes in neuronal cells. Using isoform-specific antibodies we have examined the variation in 14-3-3 isoform neurolocation in normal and scrapie-infected murine brain and show that in defined areas of the brain there are significant changes associated with the pathology of the disease process. The appearance of 14-3-3 proteins in the cerebrospinal fluid (CSF) is a consequence of neuronal disease and the detection of specific isoforms of the 14-3-3 proteins in the CSF is characteristic of some neurodegenerative diseases. In this study, monitoring specifically for the gamma 14-3-3 isoform in the CSF by both Western-blot analysis and ELISA we can show a level of correlation between the assays.

14-3-3 Proteins↗

PubMed2002

Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation.

Human lumbar CSF patterns of Abeta peptides were analysed by urea-based beta-amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western immunoblot (Abeta-SDS-PAGE/immunoblot). A highly conserved pattern of carboxyterminally truncated Abeta1-37/38/39 was found in addition to Abeta1-40 and Abeta1-42. Remarkably, Abeta1-38 was present at a higher concentration than Abeta1-42, being the second prominent Abeta peptide species in CSF. Patients with Alzheimer's disease (AD, n = 12) and patients with chronic inflammatory CNS disease (CID, n = 10) were differentiated by unique CSF Abeta peptide patterns from patients with other neuropsychiatric diseases (OND, n = 37). This became evident only when we investigated the amount of Abeta peptides relative to their total Abeta peptide concentration (Abeta1-x%, fractional Abeta peptide pattern), which may reflect disease-specific gamma-secretase activities. Remarkably, patients with AD and CID shared elevated Abeta1-38% values, whereas otherwise the patterns were distinct, allowing separation of AD from CID or OND patients without overlap. The presence of one or two ApoE epsilon4 alleles resulted in an overall reduction of CSF Abeta peptides, which was pronounced for Abeta1-42. The severity of dementia was significantly correlated to the fractional Abeta peptide pattern but not to the absolute Abeta peptide concentrations.

Adult↗

PubMed2002

Development of obsessive-compulsive behaviour following cortisone treatment.

In this report, we will describe the first case of obsessive-compulsive behaviour following oral corticosteroid treatment in a 75-year old adult male patient with pulmonary disease, but without previous psychiatric symptoms or organic brain disorder. We will also discuss the clinical and pathophysiological considerations.

Adult↗

PubMed2002

Biochemical markers of cerebrovascular injury in sleep apnoea syndrome.

Sleep apnoea syndrome (SAS) is a known risk factor for vascular diseases and stroke. Structural brain damage, manifesting as an overt neurological deficit or more subtly as cognitive dysfunction, is a frequent symptom in SAS. The presence of a biochemical marker of cerebral injury would be of great benefit in SAS to screen for even small brain damage and to monitor efficiacy of therapy. Therefore, in 10 patients with mild SAS (age 50.8+/-9.9 yrs, respiratory disturbance index (RDI) 18+/-3.6, lowest arterial oxygen saturation (min Sa,O2) 80.5+/-4.06%) and nine patients with severe SAS (age 50.3+/-11.5 yrs, RDI 75.4+/-21.7, min Sa,O2 56.56+/-14.58%), serum concentrations of neuron-specific enolase (NSE), S-100beta protein, and beta-trace were measured just before and after sleep using commercially available assays. Only serum levels in the normal range could be found, independent of when the blood was taken or the degree of SAS. Structural cerebral injury caused by sleep apnoea syndrome in patients without neurological symptoms or previous cerebrovascular events may be too small to produce a measurable increase in S-100beta, neuron-specific enolase and beta-trace serum concentrations or subclinical cerebral damage may be outside the lower detection limits of the analytical methods which were used. There is a need for biochemical markers and more sensitive methods for detecting small cerebral injury in sleep apnoea syndrome.

Adult↗

PubMed2001

Elevation of beta-amyloid peptide 2-42 in sporadic and familial Alzheimer's disease and its generation in PS1 knockout cells.

Urea-based beta-amyloid (Abeta) SDS-polyacrylamide gel electrophoresis and immunoblots were used to analyze the generation of Abeta peptides in conditioned medium from primary mouse neurons and a neuroglioma cell line, as well as in human cerebrospinal fluid. A comparable and highly conserved pattern of Abeta peptides, namely, 1-40/42 and carboxyl-terminal-truncated 1-37, 1-38, and 1-39, was found. Besides Abeta1-42, we also observed a consistent elevation of amino-terminal-truncated Abeta2-42 in a detergent-soluble pool in brains of subjects with Alzheimer's disease. Abeta2-42 was also specifically elevated in cerebrospinal fluid samples of Alzheimer's disease patients. To decipher the contribution of potential different gamma-secretases (presenilins (PSs)) in generating the amino-terminal- and carboxyl-terminal-truncated Abeta peptides, we overexpressed beta-amyloid precursor protein (APP)-trafficking mutants in PS1+/+ and PS1-/- neurons. As compared with APP-WT (primary neurons from control or PS1-deficient mice infected with Semliki Forest virus), PS1-/- neurons and PS1+/+ neurons overexpressing APP-Deltact (a slow-internalizing mutant) show a decrease of all secreted Abeta peptide species, as expected, because this mutant is processed mainly by alpha-secretase. This drop is even more pronounced for the APP-KK construct (APP mutant carrying an endoplasmic reticulum retention motif). Surprisingly, Abeta2-42 is significantly less affected in PS1-/- neurons and in neurons transfected with the endocytosis-deficient APP-Deltact construct. Our data confirm that PS1 is closely involved in the production of Abeta1-40/42 and the carboxyl-terminal-truncated Abeta1-37, Abeta1-38, and Abeta1-39, but the amino-terminal-truncated and carboxyl-terminal-elongated Abeta2-42 seems to be less affected by PS1 deficiency. Moreover, our results indicate that the latter Abeta peptide species could be generated by a beta(Asp/Ala)-secretase activity.

Aged↗