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J Wiltfang

Publications and source records attributed to J Wiltfang.

At least 37 records · Page 2Linked to original sources
PubMed2005

Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia.

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Abeta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

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PubMed2004

Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease.

Measuring proteins in cerebrospinal fluid (CSF) has gained wide acceptance for the differential diagnosis of dementia. Some groups have already extended these investigations in Alzheimer's disease (AD) by asking how stable these markers are in follow-up analysis, if they depend on the stage of disease and whether they can be used to monitor the progression and biological effects of treatment. We evaluated 21 patients with dementia with Lewy bodies (DLB) and 19 patients with AD, on two occasions, with regard to levels of tau protein, tau protein phosphorylated at threonine 181 (p-tau), Abeta42, Abeta40 and S-100B protein, using a set of commercially available assays. Tau protein levels were lower in DLB in first and second LP compared to AD and decreased during course of both groups. P-tau levels were increased in AD and DLB and decreased during follow-up. Abeta42 and Abeta40 remained relatively stable during follow-up but we found a slight increase of the median Abeta42 level in DLB, whereas in AD, Abeta42 tends to decrease during follow-up. S-100B protein increased during follow-up in both diseases. The protein dynamics in DLB and AD are relatively similar. S-100B protein may be a useful marker for follow-up in neurodegenerative diseases but has to be analysed in longer follow-up periods. Tau protein may be used to differentiate between DLB and AD. Follow-up CSF analyses are of limited value for the differentiation of AD and DLB. We conclude that more specific markers have to be established for the differentiation and follow-up of these diseases.

Acetylcholinesterase↗
PubMed2004

[Neurochemical early and differential diagnostics for Alzheimer's disease].

Current medication procedures for Alzheimer's dementia (AD) such as inhibitors of acetyl cholinesterase or Memantine and future therapeutic approaches demand improved early diagnostics. However, the differentiation between early cognitive impairments due to primary progressive demential conditions and cognitive deficits in geriatric or depressive people is a great clinical challenge. The detection of biochemical markers such as beta-amyloid peptide and tau proteins in the cerebrospinal fluid can lead to improved diagnostics of the early stages and premonitory symptoms of AD. As a result, future preventive drug treatment strategies can be employed early and selectively.

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PubMed2004

[Experimental pilot study on surface activation of implants with liposomal vectors].

BACKGROUND: Surface coating with mitogenic or morphogenic proteins can improve the healing of bone adjacent to implants and increase the bone-implant interface. Clinical surveys have shown liposome-mediated gene transfer to be a promising and safe new therapeutic method. The aim of our study was to evaluate an experimental model of new approaches for topical treatment of the implant surface and of periimplant defects by using DNA liposomes encoding for BMP-2 (bone morphogenetic protein). MATERIAL AND METHODS: A total of 27 implants (3.5 x 14 mm) were placed in critically sized defects of the frontal skull bone of adult pigs (n=3). The bottom of the implant was placed in the base of the defect which guaranteed primary stability, whereas the superior part of the implant (10 mm) represented an implant in a defect area. Liposomes containing DNA encoding for BMP-2 and GFP (green fluorescence protein) were used. In a first trial GFP-DNA liposomes on a collagen matrix were directly applied to the periimplant defect. In a second stage, the surface of the implants was encoded with BMP-2 DNA liposomes. Subsequently, these implants were inserted in the manner described. The resulting bone samples were prepared for immunohistochemical staining. Staining for GFP was performed in the area of the defect and for BMP-2 on the bone-implant interface. RESULTS: Immunohistochemical staining on day 3 postoperatively revealed an increased GFP expression in the periimplant defect. Therefore, the effectiveness of the liposomal vector was verified for the chosen animal model. On the surface of the implants encoded with BMP-2 DNA liposomes an increased BMP-2 expression was found. Thus, the liposomal vector system was validated also for BMP-2 DNA transfer in the chosen animal model. Further, the established system allows a sustainable and delayed release of BMP-2 in the area of the bone-implant interface. CONCLUSIONS: As a result of the study we were able to collect data concerning the influence of implant surface conditioning on the bone-implant interface and on therapeutically relevant options for the treatment of periimplant defects. These approaches are currently being evaluated in a long-term study.

Animals↗
PubMed2004

Efficacy of flupirtine on cognitive function in patients with CJD: A double-blind study.

BACKGROUND: In cell culture experiments, flupirtine maleate (FLU), a triaminopyridine compound, was able to protect neuronal cells from apoptotic cell death induced by prion protein fragments and beta-amyloid peptides. As FLU is a clinically safe drug, the authors started a double-blind placebo-controlled study in patients with Creutzfeldt-Jakob disease (CJD). METHODS: Twenty-eight patients with CJD were randomized to an oral treatment with either FLU (n = 13) or matching placebo (PLA; n = 15). For inclusion and continuing the study, the patients had to achieve at least 50% in two of the subscales of the dementia tests employed. A battery of standardized questionnaires was employed to monitor the progression of the disease. The main outcome variable was the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog); the difference between baseline and the best score under treatment was defined as the primary efficacy variable for hypothesis testing. RESULTS: CJD types were homogeneously distributed among the treatment groups. Patients treated with FLU showed significantly less deterioration in the dementia tests than patients treated with PLA. The mean change in ADAS-Cog (baseline to best) was +8.4 (+/-15.3) in the FLU group and +20.6 (+/-15.1) in the PLA group (p = 0.02, one-sided t-test). CONCLUSIONS: FLU has beneficial effects on cognitive function in patients with CJD. These positive results also may suggest a treatment potential of FLU in other neurodegenerative disorders. However, further studies are necessary.

Adult↗
PubMed2004

[Applying an osteoinductive protein complex for regeneration of osseous defects].

INTRODUCTION: Growth factors are still not commercially available for routine clinical use. One possibility might be the application of Colloss, which is supposed to have osteoinductive properties. Therefore, it was the aim of the following animal experimental study to compare Colloss with autogenous bone and to investigate its osteoproductive potential. MATERIAL AND METHODS: In 24 pigs clinically relevant defects were created in the forehead area. Defects were filled with autogenous bone and Colloss. One defect was left unfilled and served as control. After 2, 4, 12 and 26 weeks, six animals were sacrificed and microradiography, light microscopy and immunohistochemistry were carried out using BMP-2 and osteocalcin as antibodies. RESULTS: After 2 weeks the defects filled with the bovine protein complex showed a mineralization of 52.6% +/-4.03 compared to autogenous bone (38% +/-9.9; p=0.068) and the control defect (30% +/-2.94; p=0.05). After 4 weeks the results became assimilated. Light microscopy revealed especially after 2 weeks an enhanced de novo bone formation in the Colloss-group. This was also evident in an early expression maximum of BMP-2 after 2 weeks. Autogenous bone and the control defect showed a later expression maximum. CONCLUSION: Colloss showed an acceleration of bone regeneration in the early phase. Nevertheless, after 26 weeks the results were comparable with the autogenous bone group.

Animals↗
PubMed2004

De novo bone formation using bovine collagen and platelet-rich plasma.

In order to regenerate critical-size bone defects, a variety of bone substitutes is used in addition to autogenous bone. The regenerative capacity of these bone substitutes is usually compared to the efficacy of autogenous bone known as the "golden standard". Different cytokines influence the regeneration process because of their morphogenic or mitogenic properties. Platelet-rich plasma (PRP), a platelet concentrate, is characterised by having a positive effect on wound healing, reducing bone graft resorption and increasing the density of bone transplants. This experiment was commenced with a view to studying the osseous defect regeneration after placing various combinations of "filler materials" in experimentally created defects in the forehead of adult pigs. Regeneration by means of grafted autogenous bone (Group 1) or a bovine collagen based medical device (Group 4) alone and combined with PRP in two concentrations (Groups 2, 3, 5 and 6) was evaluated by means of microradiography and light microscopy after 2, 4 and 12 weeks. The microradiographic and light microscopic findings showed that autogenous bone in combination with PRP (Groups 2 and 3) had a significant accelerating effect on early bone regeneration (2 weeks). This effect was not evident when PRP was added to the bovine collagen (Groups 5 and 6). When using the collagen alone, significantly higher mineralisation values were achieved after 2 and 4 weeks than when using autogenous bone alone. After a 12-week observation period, the existing differences between the healing processes in the various groups were more or less levelled out. In summary, the results of the study indicate that clinically autogenous bone, as expected, is the ideal defect filler. Combining autogenous bone with PRP did not provide significantly better results. The findings in the groups treated with bovine collagen indicate that its local application mimics the effect of autogenous bone and amplifies bone regeneration when comparing with the control defect.

Animals↗
PubMed2004

In vitro cultured autologous pre-confluent oral keratinocytes for experimental prefabrication of oral mucosa.

The reconstruction of large defects after head and neck cancer resection often requires composite tissue transfer to replace a combination of bone, muscle and mucosa. Thus, tissue engineering techniques may be useful for oral mucosal reconstructive surgery to prefabricate mucosal tissue on the muscle flap in vivo, instead of using conventional skin-bearing composite flaps. The aim of this study was to investigate whether autogenous pre-confluent oral keratinocytes (PCOK) cultured in vitro can create mucosal coverage on muscle in vivo, in a single grafting procedure. In 30 Wistar rats, with a small piece of oral mucosa (2 mm x 5 mm), oral keratinocytes were isolated and then seeded on a hydrophilic PTFE membrane (n = 50) in serum-free culture condition. After 48 h, the membrane, together with the PCOK, was transplanted onto the gracilis muscle to fabricate a mucosal flap in vivo. The wound bed was closed primarily until the time of examination. Biopsies were carried out 1, 2, 3, and 4 weeks, respectively, after transplantation and were evaluated immunohistochemically (AE1/AE3 anti-pancytokeratin, cytokeratin 5/6, collagen IV, laminin, lectin-specific labeling of N-acetylglucosamine oligomeres of endothelial cells) with relation to the following criteria: (1) graft acceptance; (2) inflammatory signs; (3) structural changes and keratinocyte lining; (4) expression of basement membrane components; and (5) vascularization. Ninety-one percent of the grafts showed uniform epithelial layers. The mean number of reconstructed epithelial cell layers was 1.7, 2.0, 1.85 and 2.7 at 1, 2, 3 and 4 weeks, respectively after transplantation (P = 0.342). Collagen IV, laminin and lectin-specific capillaries developed between the neoepithelium and the underlying muscular layer. Only two specimens showed signs of infection 2 weeks after transplantation. In conclusion, this experiment demonstrated that PCOK grafts on muscle in vivo can achieve uniform multi-layered oral epithelial coverage in a short period of time. This technique may be a useful alternative tool for oropharyngeal reconstructive surgery and is also worth considering for further clinical studies.

Acetylglucosamine↗
PubMed2004

Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment.

Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) beta-amyloid(1-42) (Abeta(1-42)) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Abeta(1-42) and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Abeta(1-42) and CSF tau. The levels of CSF tau were increased, whereas levels of Abeta(1-42) were decreased in MCI subjects. Abeta(1-42) predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Abeta(1-42), but not other predictor variables (tau protein, gender, age, apolipoprotein E epsilon4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (P<0.05). Our findings support the notion that CSF tau and Abeta(1-42) may be useful biomarkers in the early identification of AD in MCI subjects.

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PubMed2004

Hertel exophthalmometry versus computed tomography and optical 3D imaging for the determination of the globe position in zygomatic fractures.

It has been the aim of the present study, to introduce the combination of computed tomography and optical 3D imaging to exophthalmometry and to compare the resulting data to the classic Hertel method. Twenty patients without orbital pathology and 12 patients were included in the study, who were subjected to a preoperative computed tomography. Optical 3D images of the facial surface were assessed and Hertel exophthalmometry was carried out to determine protrusion. In patients with zygomatic fractures the assessment of optical 3D images and Hertel values was repeated 5 days after surgery. Preoperative axial CT slices and postoperative optical contours through the globes were superimposed and the change in protrusion was determined. The protrusion values assessed either by CT, Hertel exophthalmometry or optical 3D imaging for patients without orbital pathology did not show any statistically significant differences between each other. For zygomatic fractures, Hertel exophthalmometry revealed more pronounced protrusion data in four of five cases of a posterolaterally dislocated lateral orbital rim and a higher degree of enophthalmos in cases without dislocation of the lateral orbital rim than it could be proved in the CT slices. The differences between optical measurements and CT data were minimal in patients with zygomatic fractures. The combination of computed tomography as baseline measurement and optical 3D imaging for the follow-up examinations reveal more realistic data in cases of zygomatic fractures than Hertel measurements and should be preferred.

Adult↗
PubMed2004

Morbidity of harvesting of bone grafts from the iliac crest for preprosthetic augmentation procedures: a prospective study.

It has been the aim of the present prospective clinical study to assess the morbidity following the harvest of bone from the anterior and posterior ilium in elective preprosthetic augmentations. Fifty consecutive healthy patients (30 female, 20 male, mean age 52.5+/-9.3 years, range 31 years to 65 years) underwent augmentations of implant sites by iliac crest bone grafts. The bone harvest was carried out in 25 cases from the anterior and in 25 cases from the posterior ilium. The superficial sensory function of the skin was determined quantitatively preoperatively, 7 and 30 days after surgery with the 'Pain and Thermal Sensitivity' Test (PATH Test). On the same occasions subjective pain on a visual analogue scale (VAS) and gait disturbances were documented. In the PATH Test, for the innervation areas of the lateral femoral cutaneous nerve (LFCN) and the superior and middle cluneal nerves (SMCN) a significant impairment of the superficial sensory function could be found after 1 week and a significant tendency towards recovery after 1 month (warm stimulus(FCNpreop) 37.9+/-3.0 degrees C, warm stimulus(LFCNday7): 38.6+/-3.2 degrees C, warm stimulus(LFCNday30): 37.9+/-2.9 degrees C, P(LFCNwarmpreop/day7)=0.023,P(LFCNwarmpreop/day30) =0.886, warm stimulus(SMCNpreop): 36.1+/-2.4 degrees C, warm stimulus(SMCNday7): 36.6+/-2.3 degrees C, warm stimulus(SMCNday30): 36.3+/-4.0 degrees C,P(SMCNwarmpreop/day7) <0.0005,P(SMCNwarmpreop/day30) =0.086). Gait disturbances were seen in seven patients after anterior and in three patients after posterior bone harvest 7 days after surgery (P(gaitdisturbanceanterior/posterior)=0.123). After 1 month none of the patients of both groups showed gait disturbances any longer. The maximum subjective pain level was found on the second postoperative day in both groups. It was significantly higher for the anterior approach (VAS(anteriorday2) 7.0+/-1.5, VAS(posteriorday2) 5.5+/-1.8,P(VASanterior/posteriorday2) =0.004). At day 7 and at day 30, the pain levels did no longer differ significantly (VAS(anteriorday7) 3.7+/-1.4, VAS(posteriorday7) 3.2+/-1.6,P(VASanterior/posteriorday7) =0.165, VAS(anteriorday30) 1.4+/-0.7, VAS(posteriorday30) 1.4+/-0.8,P(VASanterior/posteriorday30) =0.724). Because of the lower morbidity of bone harvest from the posterior ilium in the early postoperative phase compared to the anterior approach it seems that it should be preferred in elective augmentation procedures.

Adult↗
PubMed2004

The etiopathogenesis of schizophrenias.

There is no generally accepted model explaining the aetiopathogenesis of schizophrenias. In recent years, hypotheses with a focus on single aspects of neurotransmission, single major genetic loci or single brain areas were predominating. Now, these different approaches converge to systemic models including neurotransmission, genetic changes and neurodevelopmental malformation of brain structures. Such systemic models will explain more aspects of schizophrenias than the recent confined hypotheses.

Animals↗
PubMed2004

Lithium decreases secretion of Abeta1-42 and C-truncated species Abeta1-37/38/39/40 in chicken telencephalic cultures but specifically increases intracellular Abeta1-38.

We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Abeta) peptide formation in primary chicken telencephalic neurons, because their Abeta peptide sequence is identical to humans. As detected by quantitative Abeta-SDS-PAGE/immunoblot, Abeta peptides 1-40/42 and three additional C-truncated species, namely Abeta1-37/38/39 were regularly released into the supernatant. The highly conserved Abeta quintet strongly resembles the pattern of Abeta peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Abeta peptides 1-33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Abeta1-42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Abeta peptide secretion as well as intracellular Abeta peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Abeta1-37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Abeta1-38 while Abeta1-40 and Abeta1-42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Abeta peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Abeta1-38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Abeta peptide production.

Amyloid beta-Peptides↗
PubMed2003

Homocysteine induces cell death of rat astrocytes in vitro.

From several disease states as well as from animal models homocysteine is known to be toxic to the central nervous system. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic, apoptotic, and oxidative injury in vitro and in vivo. Both beneficent and deleterious effects of astrocytes in the pathogenesis of different neurodegenerative disorders have been described. However, data about the neurotoxic effect of homocysteine on astrocytes are lacking. The present study therefore was undertaken to investigate a possible cytotoxic effect of homocysteine on cortical astrocytes in vitro. Exposure to D,L-homocysteine resulted in a time and dose-dependent gliotoxic effect at doses of 2 mM and above (P<0.001). This is comparable to homocysteine toxicity observed in other cell culture models and implies that a participation of astrocytes in homocysteine-induced neurodegeneration may be considered. The results of the present in vitro studies may therefore have implications for understanding the pathogenesis of neurotoxicity linked to neurodegenerative disorders (e.g. Alzheimer's disease, glaucomatous optic neuropathy). This is the first study to report that homocysteine induces cell death of astrocytes. The mechanisms by which homocysteine induces cell death of astrocytes warrant further study.

Animals↗
PubMed2003

[In vitro effect of taurolidine on squamous cell carcinoma in the oral cavity].

Taurolidine (Taurolin) is a derivative of the amino acid taurine, successfully used in the treatment of peritonitis. In vitro and in vivo studies have shown that taurolidine inhibits cell proliferation and induces apoptosis in a variety of tumor cell lines. At present there are no published studies on the use of taurolidine in the treatment of squamous cell carcinoma. Our aim was to examine the inhibition of cell proliferation and induction of apoptosis in cell lines SCC 4 and SCC 15 treated with taurolidine in concentrations of 0.01%, 0.1%, and 0.5%. Analogue to the present investigations on adenocarcinoma cell lines, we used toxic antiseptic povidone iodine in the same concentration as for the reference group. Untreated cells were used as a control group. The cells were incubated with taurolidine or povidone iodine once for 2 h at 37 degrees C in 5% CO(2). Cell proliferation was assessed using WST-1 labeling kit after 3, 24, 48, 72, and 96 h. The additional measurement of cell apoptosis was examined using ELISA(PLUS) cell death detection kit and performed after 0, 24, and 48 h. The findings showed a significant inhibition of cell proliferation and induction of apoptosis in taurolidine-treated cells SCC 4 and SCC 15 in contrast to the reference group treated with povidone iodine or the untreated control group.

Antineoplastic Agents↗
PubMed2003

[Osseous defect regeneration using autogenous bone alone or combined with Biogran or Algipore with and without added thrombocytes. A microradiologic evaluation].

In addition to autogenous bone, a variety of bone substitute materials is used to regenerate bony defects. The aim of the study was to evaluate the reossification of critical size defects in the os frontale of adult pigs ( n=16) with microradiography. The defects were filled randomly with autogenous bone or the bone substitute materials Algipore and Biogran each combined with a defined quantity of autogenous bone. Additionally, platelet-rich plasma (PRP) was added in defined quantities (0.5 ml) in two different concentrations (4-fold and 6.5-fold). At 2, 4, 12, and 26 weeks four animals were sacrificed and the osseous regeneration documented by quantitative evaluation of the microradiographic findings. Microradiographic results in the autogenous bone group showed an earlier PRP concentration-dependent mineralization. Over the whole observation period the peak value of autogenous bone as filler alone could not be reached in both PRP groups. Using Algipore, no accelerated effect of mineralization however could be observed. In our study, Biogran proved to be a defect filler only partially suitable for bony defect healing, no matter whether PRP was added or not.

Alginates↗
PubMed2003

[German-speaking memory clinics: state of the art and practical recommendations].

The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in Göttingen, Germany was an optimal opportunity to make an inventory about the state of the art in diagnostic and therapy of dementia and mild cognitive impairment in German-speaking memory clinics. Several problems were discussed including difficulties in 1) diagnosis of patients with aphasia or foreign patients, 2) handling of demented patients without a caregiver, 3) psychological support for patients, who have been diagnosed in a very early stage, 4) misunderstandings between general practitioners, neurologists and psychiatrists in private practice on the one hand and the memory clinics on the other hand, 5) recommendations for prevention of dementia, 6) recommendations concerning dementia and car driving and 7) questions of genetic counselling. The following paper is a summary of the results of a workshop in Göttingen and gives practical recommendations based on the experiences of the memory clinics.

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