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Biomedical subjects

J Wiltfang

Publications and source records attributed to J Wiltfang.

At least 19 recordsLinked to original sources
PubMed2006

The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma.

AIMS: In light of recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of interleukin-8 gene (IL-8) to increased risk of oral cancer. METHODS: The IL-8 (-251 A/T) polymorphism, which influences IL-8 gene expression, was evaluated by restriction fragment length polymorphism analysis in DNA samples of 158 German and Greek patients with oral squamous cell carcinoma and 156 healthy controls of equivalent sex, ethnicity and age. RESULTS: Significant increase of mutant (A-251) allele, which results in higher IL-8 gene expression, was observed in all patients in comparison to normal controls (P<0.001). The A/T heterozygotes had a two-fold greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer compared to normal TT homozygotes. Furthermore, significantly increased values of mutant allele frequencies compared to controls were observed in all patients as well as in subgroups of patients with or without positive history of cancer (P<0.05 and P<0.001, respectively) and with or without positive history of thrombophilia (P<0.05 and P<0.001, respectively). CONCLUSIONS: In light to known observations of elevated plasma levels of IL-8 in several types of cancer including oral squamous cell carcinoma, the findings of this study suggest that the mutant allele of the (-251 A/T) polymorphism may be a major contributing genetic factor to risk for oral cancer.

Adult↗
PubMed2006

Memantine fails to facilitate partial cigarette deprivation in smokers--no role of Memantine in the treatment of nicotine dependency?

The efficacy of Memantine in the treatment of nicotine dependency in humans remained to be evaluated. The aims of our pilot study were to investigate (1) the effectiveness of Memantine in facilitating smoking reduction and (2) the influence of Memantine on the perception of nicotine. In order to achieve these aims we conducted a placebo controlled double-blind parallel group study in smokers (n = 20 per group). Before the beginning of the treatment-phase (10/20 mg Memantine per day) all participants were instructed to reduce smoking (partial deprivation). Before and during partial deprivation we registered the daily cigarette consumption and craving estimates. Following nasal stimulation with nicotine enantiomers hedonic and intensity estimates and the discrimination ability were assessed. Memantine failed to facilitate smoking reduction and did not influence the perception of nicotine with the exception of a weak reduction of olfactory intensity estimates reaching statistical significance for one nicotine enantiomer only.

Adult↗
PubMed2006

Decreased circulating CD34+ stem cells in early Alzheimer's disease: Evidence for a deficient hematopoietic brain support?

Hematopoietic stem cells contribute to mammalian brain tissue regeneration by transdifferentiation processes. We found decreased counts of circulating CD34+ cells in early Alzheimer's dementia (AD; P = 0.01), which significantly correlated with age (r = -0.661; P = 0.001), cerebrospinal fluid beta-amyloid (Abeta)1-42 (r = -0.467; P = 0.025) and most pronounced the Abeta42/40 ratio (r = -0.688; P = 0.005). Our data suggest a deficient regenerative hematopoietic support for the central nervous system in early AD.

Alzheimer Disease↗
PubMed2006

CSF diagnosis of Alzheimer's disease and dementia with Lewy bodies.

Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often crucial. CSF Tau protein and Amyloid-beta (A beta) peptides have shown diagnostic value for the diagnosis of AD, but discrimination from DLB was poor.Herein, we investigate CSF of 18 patients with probable AD, 25 with probable DLB and 14 non-demented disease controls (NDC) by A beta-SDS-PAGE/immunoblot and commercially available ELISAs for A beta1-42 and tau. CSF A beta peptide patterns and tau exhibited disease specific alterations among AD and DLB. The ratio of A beta1-42 to A beta1-38 and A beta1-42 to A beta1-37, respectively, in combination with absolute tau, yielded a sensitivity and specificity of 100 and 92%, respectively. We conclude that CSF A beta peptide patterns and tau levels reflect disease-specific pathophysiological pathways of these dementias as distinct neurochemical phenotypes. Combined evaluation of these biomarkers provides a reasonable accuracy for differential diagnosis of AD and DLB.

Aged↗
PubMed2006

The German Competence Net Dementias: standard operating procedures for the neurochemical dementia diagnostics.

Aging of population results in an increasing number of patients with dementia. Therefore, recently a BMBF-supported project, Competence Net Dementia, was launched to reveal diagnostic, therapeutic, and epidemiologic aspects of demential disorders. In this project, our task was to establish and maintain human body fluids (HBF) bank to collect cerebrospinal fluid, plasma, serum, and full blood of patients enrolled into the study. As the pre-analytical sample handling is a prerequisite of all studies aiming at finding novel disease biomarkers, standard operating procedures (SOPs) were launched by our group to allow standardized collection, storage, and shipment of the samples among all 14 University centers involved in HBF collection. Currently, to our best knowledge the CND HBF bank represents one of the largest prospectively collected set of the samples from subjects with mild cognitive impairment and early dementias. With the samples collected in the HBF bank, recently introduced analytical technologies (like e.g. surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), differential gel electrophoresis (DIGE), and multiplexing) can be promptly tested with regard to their potential usefulness in neurochemical dementia diagnostics.

Brain Chemistry↗
PubMed2006

Plasminogen activator inhibitor-1 polymorphism is associated with increased risk for oral cancer.

In light of the recently observed contribution of thrombosis-related factors to carcinogenesis, we investigated the possible association of plasminogen activator inhibitor-1 (PAI-1) with increased risk for oral cancer. In DNA samples of 104 patients with oral squamous cell carcinoma and 106 healthy controls of comparable ethnicity, age and sex, we studied the 4G/5G polymorphism in the PAI-1 gene, which affects its expression. The mutant 4G allele and carrier frequencies were significantly increased in patients compared to controls (65.9% versus 49.5%; 88.5% versus 69.8% respectively, P<0.01). That increase was even higher in patients with a positive family history for thrombophilia or without one for cancer (P<0.001). Interestingly, significant difference from controls was observed only in patients with cancer stages I and II. These findings suggest that the 4G allele, by resulting in higher PAI-1 expression, is a major contributing factor in early stages of oral oncogenesis. Possibly, increased PAI-1 promotes initial development of oral cancer through regulation of cell detachment and delays further tumor progression by inhibiting vascularization.

Adult↗
PubMed2006

Association of platelet glycoprotein Ia polymorphism with minor increase of risk for oral cancer.

AIMS: In light to association of increased platelet glycoprotein Ia (GPIa) expression with tumor invasion and metastasis in several types of cancer, we investigated the possible contribution of a common polymorphism (C807/T807), affecting the GPIa gene expression, in the development of oral cancer. METHODS: DNA samples of 110 patients with oral cancer and 114 healthy controls were examined by allele-specific polymerase chain reaction followed by electrophoretic analysis. RESULTS: The mutant T807 allele homozygotes were significantly increased in the group of patients compared to the control group (P < 0.001). Furthermore, significantly increased frequency of mutant alleles compared to controls was observed in the subgroup of patients with a positive history for cancer (P < 0.01). CONCLUSIONS: The obtained results indicate that the C807/T807 polymorphism is indeed a genetic predisposing factor which contributes to increased risk for oral cancer.

Alleles↗
PubMed2006

Intraoral lesions associated with sebaceous nevus syndrome.

The sebaceous nevus syndrome describes the rare association of a sebaceous nevus with systemic features such as mental retardation, seizures and colobomas (among others). It is thought to be a cutaneous mosaic inherited as a paradominant trait. Three cases are provided illustrating the intraoral manifestations of the syndrome. The first histological comparison of contiguous mucosal and cutaneous lesions is provided. We also describe the possible association of SFM syndrome with a benign fibrous histiocytic lesion of the mandible. This and other mandibular tumors associated with the sebaceous nevus syndrome may have significant implications for patients. Awareness of the potential presence or development of significant intraoral lesions in association with the sebaceous nevus syndrome is important for those involved in the care of patients with this syndrome.

Abnormalities, Multiple↗
PubMed2005

Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer.

PURPOSE: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair. METHODS: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex. RESULTS: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls. CONCLUSIONS: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.

Adult↗
PubMed2005

Innate immunity in human bone.

Bone has exceptional regenerative properties. Oral bone appears to be particularly resistant to infection despite exposure to oral flora, even in circumstances such as oral surgery where the thin mucosal layer covering the bone is disrupted. The goal of this study was to determine whether the innate immune system of antimicrobial peptides exists inside bone. Biopsies of non-infected and chronically infected mandibular bone were harvested from patients during maxillofacial surgical procedures. Bone biopsies from the iliac crest and fibula served as controls. Immunohistochemical staining was performed, directed against the human beta-defensin antimicrobial peptides (hBD) -1, -2 and -3. In addition, cultures of osteoblast-like cells were examined for the presence of each of the three beta-defensins and their mRNA transcripts. All three human beta-defensins were detected within the mineralized bone matrix of chronically infected mandibular bone in the vicinity of the endosteum and osteocytes. hBD-1, -2 and -3 were also found in the cytoplasm of osteocytes. Expression of all three beta-defensins was detected in each of the non-infected bone types including the controls, however, to a lesser degree than that found in the chronically infected mandibular bone. This may reflect upregulation of antimicrobial peptide expression in the presence of chronic infection. Cultures of non-infected osteoblast-like cells were found to express mRNA for each of hBD-1, -2 and -3. Immunohistochemical staining of the cultures was positive for hBD-1 and -2, but not for hBD-3. We provide the first evidence of a previously unrecognized innate immunological function of bone through the demonstration of the presence of the human beta-defensins hBD-1, -2 and -3 in bone.

Alkaline Phosphatase↗
PubMed2005

Antibacterial essential oils in malodorous cancer patients: clinical observations in 30 patients.

Malodorous necrotic ulcers in cancer patients are of major concern as it leads to social isolation and poor quality of life. Current medications and topical therapies have proven inadequate in their ability to reduce foul smell to acceptable levels. We report the positive experience we have had in using antibacterial essential oils in patients with incurable head and neck cancer and associated malodorous necrotic ulcers. All patients received a standard course of therapy with oral or systemic antibiosis. In addition, we rinsed the ulcers with an antibacterial essential oil mix (mainly based on Eucalyptus oil) twice a day. All patients experienced complete resolution of the foul smell by only the third or fourth day of therapy. As a secondary effect we saw that besides smell reduction the oils had anti-inflammatory effects on neoplastic ulcers. In some patients ulcers started to heal and achieved complete re-epithiliazation. The patients experienced great personal relief upon resolution of their malodorous conditions. Quality of life improved significantly with the resulting reintroduction of social contact with friends and relatives.

Aged↗
PubMed2005

Region specific distribution of levomepromazine in the human brain.

OBJECTIVE: The aim of this study was to examine concentrations of levomepromazine and its metabolite desmethyl-levomepromazine in different regions of human brain and in relationship to drug-free time. METHODS: Drug concentrations were measured in up to 43 regions of 5 postmortem human brains of patients previously treated with levomepromazine. To enable statistical comparison across brain regions several smaller brain areas were put together to form larger brain areas (cortex cerebri, limbic system, cerebellum, basal ganglia, thalamus). Mean values of drug concentrations in these larger brain areas were used in a repeated measurement ANOVA to analyze for region specific distribution. The elimination half-life in brain tissue was estimated with a NONMEM population kinetic analysis using the mean value of all brain regions of an individual case. RESULTS: Levomepromazine and desmethyl-levomepromazine appear to accumulate in human brain tissue relative to blood. Mean concentrations differed largely between individual brains, in part due to differences in dose of drug, duration of treatment and drug-free time before death. There was an apparent region-specific difference in levomepromazine concentrations with highest values in the basal ganglia (mean 316 ng/g) and lowest values in the cortex cerebri (mean 209 ng/g). The elimination half-life from brain tissue is longer than from blood and was calculated to be about one week. Similar results were obtained with desmethyl-levomepromazine. CONCLUSIONS: Levomepromazine shows a region-specific distribution in the human brain with highest values in the basal ganglia. This might be the consequence of low expression of the metabolic enzyme Cyp2D6 in the basal ganglia. If this finding is true also for other neuroleptic drugs it might increase our understanding of preferential toxicity of neuroleptic drugs against basal ganglia structures and higher volumes of basal ganglia of neuroleptic-treated patients. Furthermore, patients exposed to levomepromazine cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.

Aged↗
PubMed2005

Onlay augmentation versus sinuslift procedure in the treatment of the severely resorbed maxilla: a 5-year comparative longitudinal study.

Augmentation procedures in the severely resorbed maxilla are standard techniques in preprosthetic surgery. Aim of the present study was to compare onlay bone grafting and sinus floor elevation with autogenous bone grafts in edentulous patients in terms of bone resorption of the posterior alveolar crest and implant survival in a 5-year longitudinal study. A total of 100 patients (53 female and 47 male patients) requiring augmentation using autogenous bone due to a severely resorbed maxillae were evaluated. The degree of resorption and bone quality were preoperatively estimated in panoramic radiographs according to Lekholm and Zarb. The overall 5-year success rate of implants placed after augmentation procedures in the posterior maxilla was 93.1%. Following onlay augmentations 215 out of 235 implant insertions were successful, i.e. a success rate of 91.5% was achieved. In the sinuslift group, 330 out 349 implants remained successful, i.e. a success rate of 94.6% was found. The difference between both groups was statistically significant at the end of the evaluation period. Bone resorption, measured as loss of total bone height in panoramic radiographs, was initially more pronounced following onlay augmentations (>20% after 12 months of observation). The degree of resorption decreased in the further course of the study. Lower resorption rates and a higher overall success rate were demonstrated for the sinus lift group.

Adult↗
PubMed2005

High activity of acid sphingomyelinase in major depression.

Acid sphingomyelinase (A-SMase) and its reaction product ceramide may play a role in the pathophysiology of depressive disorders and in the therapeutic action of antidepressive drugs. In a prospective case-control study, A-SMase activity was measured in peripheral blood mononuclear cells of 17 patients with a major depressive episode who were free of antidepressant drug therapy for at least 10 days and 8 healthy volunteers. In the patient group, A-SMase activity was correlated to the score (n=17, r=0.64, P=0.005). The patient group exhibited higher A-SMase activity compared to healthy volunteers (T=2.09, df=21.33, P<0.05). In addition, we demonstrate that the antidepressants imipramine and amitriptyline induce a long-term reduction of the activity of A-SMase in cultured cells.

Adult↗
PubMed2005

[Critical odontogenic infection involving the mediastinum. Case report].

BACKGROUND: Occasionally, trivial odontogenic infections may develop into complex diseases. This may even result in an unrestrained phlegmonous spread causing life-threatening complications. These problems have decreased since the introduction of antibiotics and also due to improved oral hygiene and improved diagnostic measures resulting in optimized medical treatment. However, life-threatening forms are still seen, in particular if infections spread along the cervical fascial sheaths down towards to the mediastinum. Over the past decade the number of critical infections has increased in other medical specialties. This is usually explained by the development of multiresistant pathogens in the context of nosocomial infections. PATIENTS AND METHODS: We reviewed the patients' records of the past 15 years at the Department of Oral and Maxillofacial Surgery of the University Hospital Kiel to assess a possible increase of odontogenic infections with life-threatening complications. From 1990 to 2004, four patients with odontogenic infections exhibiting critical phlegmonous spread were treated in the intensive care unit. Two patients developed bacterial mediastinitis which could be controlled by intravenous antibiotics only. One patient progressed to general septic mediastinitis and eventually died of cardiorespiratory arrest. The last patient also had septic mediastinitis and developed right pleural empyema. Several operations were necessary before the disease could be controlled. This patient's case report is presented in detail. CONCLUSION: The prognosis of patients with mediastinitis crucially depends on (a) early diagnosis including computed tomography of the neck and thorax, (b) early radical surgical intervention, and (c) optimized pathogen-oriented antibiotic treatment.

Abscess↗
PubMed2005

Expression of bone matrix proteins during de novo bone formation using a bovine collagen and platelet-rich plasma (prp)--an immunohistochemical analysis.

This animal study (domestic pig) examined the bone formation after filling defined defects with autogenous bone or a collagen lyophilisat in combination with Platelet-rich-plasma (PRP) by evaluating bone matrix proteins. Six groups, both materials with and without PRP in two concentrations (+ 1, + 2) were compared to untreated bone by means of immunohistochemistry at 2, 4, 12 and 26 weeks. BMP-2 expression was increased at 2 weeks in the collagen + 1 group and after 4 weeks in the collagen + 1 and + 2 group. Collagen-I expression was increased at 2 weeks in all collagen groups. After 4 weeks raised levels were observed after adding the higher concentrated PRP to bone and the collagen material. Osteocalcin expression was enhanced at 2 weeks in all collagen groups and the autogenous bone + PRP1 group, after 4 weeks in the bone and collagen + 2 groups. At 12 weeks higher values were observed after adding higher concentrated PRP to bone. Osteonectin and especially osteopontin were confirmed to be effective markers of early bone formation in all specimens. The described setting allows to combine established techniques (microradiography, light microscopy) with approaches to explore the underlying biology (immunohistochemistry) on the same specimen.

Animals↗
PubMed2005

Effects of distraction forces and frequency of distraction on bony regeneration.

The rate and frequency of distraction have a decisive influence on the regenerative process. We tested a newly developed hydraulic osteodistractor in 12 pigs, which were assigned to have continuous and intermittent osteodistraction of the mandible after osteotomy. The forces necessary to distract the mandible were recorded during intermittent distraction. These data were then used for continuous distraction of the bone. Continuous osteodistraction resulted in intramembranous regeneration of bone, whereas intermittent osteodistraction caused chondroid ossification in the regeneration of the bone. Continuous osteodistraction caused speedier regeneration, and distraction forces were lower than with intermittent distraction.

Animals↗