Decreased CSF amyloid beta42 and normal tau levels in dementia with Lewy bodies.
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Amyloid beta-Peptides↗
Biomedical subjects
J Wiltfang
Publications and source records attributed to J Wiltfang.
Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease.
We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho-tau199) by a recently established sandwich ELISA. The CSF/phospho-tau199 levels in the AD group were significantly elevated compared to those in all the other non-AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group vs all the other non-AD groups using the CSF/phospho-tau199 were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho-tau199 and CSF/total-tau levels in the AD group. Elevated CSF/phospho-tau199 in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho-tau199 may be a novel and logical biomarker in supporting antemortem diagnosis of AD.
Aged↗
Clozapine-associated elevation of plasma cholinesterase.
OBJECTIVE: The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. METHODS: Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. RESULTS: We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. CONCLUSION: We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction.
Adult↗
Unaltered apoptotic behaviour of mononuclear cells from patients with sporadic Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform encephalopathies. It is suspected that a pathologically altered form of the prion protein (PrPSc) is the decisive trigger of the disease. Data from animal experiments suggest an involvement of the lymphatic system in the intracorporal transport of PrPSc. However, it has not so far been possible to detect PrPSc on mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we investigated the natural and induced apoptotic behaviour of these cells. MNCs from 19 patients with sporadic CJD and from 20 patients with other neurological disorders were used. The cells were analysed by fluorescence cytometry with and without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the morphological investigation of the cells before apoptosis induction, there were no significant differences between the groups with regard to cell size and granularity of the MNCs. After apoptosis induction, the typical significant decrease in cell size and increase in granularity of the cells occurred in both groups. Significant differences between the patient populations were not found. For the first time, our investigation has demonstrated that a functional impairment of MNCs with regard to their apoptotic behaviour does not occur in sporadic CJD. It remains open to question whether this mechanism plays an important role in forms of transmissible encephalopathy other than sporadic CJD, especially after oral transmission.
Adult↗
Different preparation methods to obtain platelet components as a source of growth factors for local application.
BACKGROUND: Autologous platelet components were recently used as part of tissue-engineering strategies in oral and maxillofacial surgery. Various preparation methods were investigated to define standardized blood bank components and to collect data on the growth factor content of human platelets before and after storage. STUDY DESIGN AND METHODS: Apheresis platelets (AP), buffy coat-derived platelets (BCP), platelets prepared by tube method (TP), and highly concentrated samples prepared from AP and from BCP were evaluated for standard quality criteria of platelet components and for their concentration of transforming growth factor (TGF)-ss1, platelet-derived growth factor (PDGF)-AB, and PDGF-BB. AP were stored for 5 days. On Days 3 and 5, these components and freshly prepared, highly concentrated samples were evaluated for the same measures. RESULTS: Platelet concentration in TP was lower than that in the other groups (p<0.05). However, the concentrations of PDGF-AB, PDGF-BB, and TGF-ss1 were comparable in the three groups. TP showed higher spontaneous CD62 expression than did AP and BCP. The three preparation procedures resulted in significantly different WBC contamination, with the highest levels in TP. For the whole series of measurements, there was a strong correlation between growth factor levels and platelet concentration (p<0.05), which was due to the face that the growth factor content of concentrated platelet samples was tenfold that of AP, BCP, and TP. In TP, the WBC concentration was correlated with PDGF levels (p<0.05). After 5-day storage, the mean levels of PDGF-AB, PDGF-BB, and TGF-ss1 were 57.1, 43.0, and 72.0 percent of the initial values in AP. Overall, multiple regression analysis revealed the following factors influencing the measured growth factor concentrations: platelet concentration, baseline CD62 expression, lactate production, and WBC contamination. CONCLUSION: Various methods enable the preparation of platelet components and of highly concentrated components for local use according to standard blood banking criteria. The obtained components differ, particularly in their WBC content and in vitro platelet activation. These findings are relevant for planning and evaluating further studies of locally usable autologous platelet components.
Blood Platelets↗
Distraction osteogenesis of the maxilla and midface using a subcutaneous device: report of four cases.
The use of distraction osteogenesis in the hypoplastic maxilla and midface is still controversial. Since the beginning of 1998, 25 patients have been treated with osteodistraction techniques for various reasons. Among them were four patients who were treated by high LeFort I osteotomies and insertion of a newly developed subcutaneous distraction device in the malar region. Distraction osteogenesis was successful in all four cases resulting in a mean sagittal bone gain of 12.0 mm (range 7-14) at the level of distractor fixation. All patients were kept under orthodontic supervision during osteodistraction. The final occlusal relation was satisfactory. Cephalometric measurements after distraction showed an anterior rotational movement of the midface region. As the question of relapse and further growth is still not clear, Delaire masks are used to stabilize the surgical result after removal of the distractor. The importance of long-term follow-up is stressed.
Adolescent↗
Continuous and intermittent bone distraction using a microhydraulic cylinder: an experimental study in minipigs.
Distraction osteogenesis of the mandible is an option in the treatment of mandibular hypoplasia. Today, only intermittent distraction devices are available for clinical application. The aim of this study in minipigs was to evaluate continuous bone distraction using a microhydraulic cylinder. After a seven-day interval, continuous or intermittent distraction of 1.5 mm/day was established for 10 days. Immediately after active distraction, two animals and 20 days later the other four animals were killed and radiographs taken. The mandible was then removed en bloc and the distracted bone examined histologically. Intermittent distraction forces of up to 2500 kPa were necessary to move the cylinders' piston. The pressure needed for continuous distraction was considerably lower (1200-1300 kPa). While the specific histological structure of the varying zones in the distraction gap was similar after continuous and intermittent distraction, bone healing was accelerated after continuous distraction as shown by ultrasonography and scanning electron microscopy.
Animals↗
Histomorphometric and densitometric changes in bone volume and structure after avascular bone grafting in the extremely atrophic maxilla.
AIM: To evaluate changes in volume and structure of bone after autogenous iliac crest bone grafting to the maxilla. To discover the predictive value of computed tomographic (CT) measurements of bone density and study their correlation with the results of histomorphometric analyses of bone structure. PATIENTS AND METHODS: In 25 patients with atrophic maxillae (mean age 47 years, range 15-71), who had onlay bone grafting and sinus floor augmentation with autogenous iliac crest bone, a CT analysis was carried out immediately before and after grafting, and 5 months (range 4-6) later, at the time of endosseous implantation. On both occasions, bone biopsy specimens were taken. HISTOLOGY OF BONE: After preparing and digitizing semithin sections, histomorphometry (NH-Image) was done to establish the ratio of trabeculae to medullary cavity. CT ANALYSIS: The available transverse and vertical bone and the bone density of natural and augmented bone were analyzed using the Simplant Program and the CT data. As reference, the bone density of the first cervical vertebra was used. By regression analysis, the correlation of CT bone density and histological bone structure was investigated. RESULTS: After a median healing period of 4.5 months, no significant changes were found in bone volume compared with the measurements made immediately after grafting. The changes in density in the cancellous portion of the grafted bone showed no correlation (correlation coefficient: +0.16) with the results of histomorphometric analysis of bone structure. CONCLUSIONS: The predictive value of measurement of bone density to evaluate bone structure on the basis of the D1-D4 classification needs to be reconsidered. The most favourable time for secondary implantation is 4-6 months after iliac crest bone grafting.
Adolescent↗
Langerhans cell granulomatosis: a case report of polyostotic manifestation in the jaw.
We report the case of a 43-year-old woman who suffered from a polyostotic form of Langerhans cell granulomatosis (LCG) in the mandible and maxilla. The course of the disease was followed for more than 14 years. The disease's progression finally required subtotal resection of the mandible and reconstruction with a microvascular fibula graft. The literature is reviewed for diagnostic and treatment concepts based on the different stages of LCG.
Adult↗
The role of angiography in the lower extremity using free vascularized fibular transplants for mandibular reconstruction.
BACKGROUND: Fibular osteocutaneous free tissue transfer represents the work horse procedure in the reconstruction of large oromandibular defects. Before the fibula is harvested the blood supply of the lower leg and foot should be examined, as the perfusion may be based predominantly on the peroneal artery and venae comitantes. To avoid postoperative ischaemia of the lower leg, adequate perfusion must be guaranteed before sacrificing the peroneal vessels. Anatomical variations and peripheral arterial occlusive disease add to the risk of ischaemia. Various methods of evaluating the blood supply have been described. MATERIAL AND METHODS: Fifty-two consecutive cases of fibular flaps were evaluated to study the arterial blood supply of the lower extremity. For angiography, the right femoral artery was punctured using the Seldinger technique and a total of 20-25 ml contrast medium (Imeron 300) was infused and images required at a rate of 0.5/sec. RESULTS: A patent three-vessel supply to both feet could only be detected in 21 patients. Thirty-one angiograms revealed anatomic and/or arteriosclerotic alterations. Angiography provided accurate information in all patients and allowed successful fibular transfer in those patients who were found preoperatively to have regular conditions. CONCLUSION: Preoperative assessment of the blood supply of the lower extremity is important before fibular osteocutaneous free tissue transfer. We advocate angiography as interpretation is not examiner dependent.
Adult↗
Subclinical pancreatitis related to mirtazapine - a case report.
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Alcoholism↗
[Glutamatergic neurotransmission in schizophrenics].
Glutamate is the most abundant amino acid in the brain, where it plays an important role as a well-established major excitatory neurotransmitter in the central nervous system. It has been suggested that reduced glutamate neurotransmission may be involved in the pathophysiology of schizophrenia. The glutamate hypothesis of schizophrenia postulates alterations in the glutamatergic system as an important neurobiochemical event in the pathophysiology of this group of psychotic disorders. An altered glutamate release from synaptosomes including a hypofunction of different glutamate receptors (i.e. NMDA receptors) from different brain areas have previously been reported. Furthermore, partial agonists at the glycine co-agonist site of the NMDA receptor might be a new approach in the treatment of schizophrenic symptoms but further studies are necessary to clarify the role and efficacy of these substances in schizophrenia. Changes in the glutamatergic cortico-striatal connections in schizophrenia could precipitate a potential perceptive overstimulation of the neocortex from thalamic input and an inhibiting influence of the striatum on the thalamus would modulate the information input of the cortex, thereby possibly counteracting the disturbed information processing which is relatively characteristic for schizophrenic psychoses.
Glutamic Acid↗
Intraindividual comparative animal study of alpha- and beta-tricalcium phosphate degradation in conjunction with simultaneous insertion of dental implants.
An intraindividual comparative study of proximal tibial marrow defects in nine adult Goettinger miniature pigs (GMPs) was undertaken. The left side of the defect was filled with granular beta-tricalcium phosphate (TCP) ceramic ad modum Cerasorb, and the right side was filled with granular alpha-TCP ceramic ad modum Biobase alpha pore. Simultaneously, dental screw implants were inserted in each ceramic and fixed within the orthotopically replanted corticalis lids. Control defects were made in two other animals. The survival period ranged from 4 to 86 weeks (control study, 16 and 20 weeks). The reorganization and degree of bone regeneration, dynamics of ceramic degradation, and remodeling characteristics of the bone regenerate referring to osseo-integration of the dental implants were examined histomorphologically in nondecalcified specimens. The results reveal that both ceramic types were osteoconductive exclusively. Centripetally oriented angiogene bone regeneration occurred at the margins of the circular defects. Ceramic degradation was performed hydrolytically and within cells. Furthermore, it was demonstrated that decomposition of the intratrabecularly integrated ceramic residues underlies a dynamic process of degradation. Within 86 weeks, nearly 80% to 90% of the larger alpha-TCP granules, and nearly 90% to 95% of the beta-TCP granules were degraded. At this time, especially for the alpha-TCP modification, ceramic microparticles were found in the marrow, either unbound or within polynuclear macrophages. The predictable degradation of both ceramic types provides an early functional adaptation of bone regenerates and facilitates a biofunctional, anisotropic orientation of the neotrabeculae without delay. It is concluded that because of the initially pronounced accumulation of macrophages, dental implants should not be inserted simultaneously with ceramic, but after further progress of ceramic degradation (5 to 6 months after TCP implantation).
Absorbable Implants↗
Diagnostic and prognostic relevance of expression of human telomerase subunits in oral cancer.
Telomerase activity (TA) is associated with most malignant human tumors but is not detected in normal somatic cells with a few exceptions. Three major subunits (hTR, hTP1 and hTERT) of telomerase have been identified. To investigate the clinical implications of the mRNA detection of these components as useful diagnostic and prognostic markers in oral cancer, we examined TA, hTR, hTP1 and hTERT mRNA expressions in 46 oral squamous cell carcinomas (OSCC) and 15 normal oral mucosal tissues from healthy volunteers using a highly sensitive TRAP assay and RT PCR. In all specimens hTR and hTP1 mRNA were detected regardless whether TA was expressed or not. On the contrary, a significant correlation between hTERT expression and TA was shown indicating that the activity of telomerase could be regulated by the extent of hTERT transcription. In addition, hTERT expression showed close association to malignancies. None of the normal mucosal specimens expressed the hTERT subunit, but 76% (35/46) of the tumor specimens did. None of other clinico-pathological and prognostic parameters showed significant relationship with TA or hTERT expression. These results suggest that the detection of hTERT expression may be another useful diagnostic marker, especially for early detection of OSCC, and for distinguishing healthy tissues from neoplastically transformed ones.
Carcinoma, Squamous Cell↗
Oxidative stress and an altered methionine metabolism in alcoholism.
The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearman's r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.
Adult↗
Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
OBJECTIVES: Decreased levels of Abeta1-42 are found in CSF of patients with AD. Because early stages of Creutzfeldt-Jakob disease (CJD) and AD share several clinical features, we investigated Abeta1-42 levels in CSF of these groups, inferring that this might give additional help in differentiating patients with CJD from AD patients. METHODS: We investigated 27 patients with CJD, 14 patients with AD, 19 patients with other dementias, and 20 nondemented controls (NDC) for Abeta1-42 in CSF. Twenty-four of the 27 CJD patients were neuropathologically verified. All the neuropathologically verified patients presented with a type 1 prion protein pattern. CJD patients were all homozygous for methionine at codon 129. Except in five CJD patients, no beta-amyloid plaques were seen. Additionally, APOE status was determined in patients with CJD. RESULTS: Levels of Abeta1-42 in CSF were decreased in patients with AD as well as in CJD. Levels of Abeta1-42 in CSF of patients with CJD and AD were significantly different from the other dementia and NDC groups. There was no substantial difference between the CJD and AD groups (p = 0.66). Decreased levels of Abeta1-42 did not correlate with the APOE epsilon4 load in patients with CJD. CONCLUSION: Low levels of Abeta1-42 in CSF do not exclude a diagnosis of CJD. Decreased levels of Abeta1-42 in CSF can occur without beta-amyloid plaque formation in the brain. However, the underlying mechanism of this phenomenon must be elucidated.
Adult↗
Glutamine synthetase in experimental meningitis: increased ratio of the subunits 3 and 2 may indicate enhanced activity.
Glutamine synthetase (GS) activity is higher in the neocortex but not in the hippocampal formation of rabbit brain during Streptococcus pneumoniae meningitis compared to the respective brain region of uninfected control animals. One-dimensional polyacrylamide gel electrophoresis (1D-SDS-PAGE) revealed an apparent molecular mass (M(r)) of 44000 Dalton (Da) for GS from rabbit brain. After two-dimensional gel electrophoresis (2D-PAGE), followed by Coomassie-blue staining, GS separated into three distinct spots (S1, S2, S3). One additional spot (S4) occurred on the immunoblot. All four GS spots exhibited the same M(r) (44000 Da), but differed in their isoelectric points. Densitometric evaluation of the two-dimensional maps revealed a strong increase of optical density (OD) of S3 in the frontal cortex of infected animals. The calculated OD ratio S3/S2 in the frontal cortex from rabbits with meningitis was 1.75+/-0.68 (mean+/-standard deviation). Compared to controls (0. 85+/-0.39), this value was significantly increased (p=0.0006). In the hippocampal formation, the ratio S3/S2 was nearly unchanged during meningitis. It is suggested that the ratio S3/S2 may indicate a neuroprotective feature of rabbit brain during meningitis since neuronal apoptosis occurs only in the dentate gyrus and not in the frontal cortex.
Animals↗
[Vascularization of free myocutaneous gracilis flaps in replacement transplantation after preoperative radiotherapy. An experimental study].
BACKGROUND: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes to the connective tissue and vascular endothelium are observed. These processes may lead to a delay in healing of free flaps in the irradiated transplant bed. The aim of the study was to investigate qualitative and quantitative changes in vascularization in irradiated and regular transplant beds. MATERIAL AND METHODS: In Wistar rats (male, weight 300 to 500 g) undergoing preoperative irradiation of the neck region with 3 times 10 Gy (30 animals) and 5 times 10 Gy (30 animals) and non-irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The time interval between irradiation and transplantation was 4 weeks. On day 3, 4, 5, 7, 14 and 28 post operation, the capillary sprouting, structural changes and the distribution patterns were analyzed by H & E and immunohistochemical staining (goat-F[ab]-2-anti-von Willebrand factor antibody). Three histological sections (2 to 4 microns) per sample were investigated histomorphometrically, qualitatively and quantitatively (ratio capillary area/total area, and capillary lumen) by NH-image-digitized measurement. A statistical analysis was performed using the Mann-Whitney test. RESULTS: In contrast to non-irradiated rats, irradiated animals showed a qualitatively reduced and a more irregular capillary distribution with more marked pericapillary fibrosis in the irradiated transplant bed. Quantitatively, the ratio capillary area/total area, as a marker of improved capillarization was significantly reduced in the transition area transplant/irradiated transplant bed and in irradiated transplant bed tissues in contrast to the non-irradiated control group (p = 0.004). Also, from day 14 to 28 a significant decrease was found in the transition area between transplanted tissues and irradiated transplant bed tissues in irradiated animals (p = 0.005). The median capillary lumen size also decreased significantly in the transition area and transplant bed in 30 Gy and 50 Gy irradiated animals (p < 0.001 and p = 0.003). CONCLUSIONS: Following irradiation, vascularization of the soft tissue flaps is both reduced and delayed. This is evidence of delayed healing of soft tissue transplants in transplant beds irradiated prior to surgical interventions. Further optimization of the time interval between radiotherapy and surgery and the total radiation dose are therefore needed.
Animals↗