Biomedical subjects

Thomas Kocher

Publications and source records attributed to Thomas Kocher.

50 records · Page 3Linked to original sources

PubMed2002

Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study.

TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples from 1,849 patients. In 2,090/2,317 cases (90.2%), immunostaining yielded interpretable results. Since for some patients more than 1 sample was available, only interpretable first biopsies (n = 1,628) were considered. MAGE-A4 protein was expressed at significantly (p < 0.001) higher frequency in squamous (25/55, 45.5%) than in adeno (4/15, 26.7%), sarcomatoid (4/14, 28.6%), small cell (5/20, 25%) or transitional cell (281/1,522, 18.5%) carcinomas. In TCCs, overall MAGE-A4 positivity was significantly correlated with invasive phenotype (p < 0.001) and high tumor grade (p < 0.0001). Clinical data from 908 TCC patients were retrospectively evaluated, revealing that strong 57B staining was highly significantly associated with decreased tumor-specific survival (p < 0.0001). These data suggest that evaluation of MAGE-A4 protein expression is useful in the identification of groups of TCCs characterized by severe prognosis, thus possibly providing indications for early MAGE TAA-targeted immunotherapy.

Antibodies, Monoclonal↗

PubMed2002

Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo.

A specific cellular immune response directed against a panel of three defined tumor-associated antigen (TAA) epitopes was induced in metastatic melanoma patients by a prime-boost strategy taking advantage of an innovative recombinant vaccinia virus as evaluated by quantitative assessment of cytotoxic T lymphocytes (CTLs) with corresponding specificity. The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. Boosts were subsequently applied with corresponding synthetic nonapeptides and GM-CSF. Specific CTL induction was assessed by tetramer staining and CTL precursor (CTLp) frequency evaluation. Within 12 days of injection of the recombinant vector, cytotoxic T cell responses specific for engineered epitopes were detectable in three of three patients. During the vaccination treatment, antigen-specific CTLp frequencies exceeding 1:10,000 peripheral CD8(+) T cells could be observed. Tetramer staining also revealed significant increases in specific CD8(+) T cell numbers. We conclude that active specific antitumor vaccination can raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells with heterogeneous antigen expression. Data from this study emphasize the potency of a recombinant vaccinia virus vector encoding multiple minigenes and costimulatory molecules in the context of exogenously administered GM-CSF. Clinical effectiveness of this immunologically active protocol should therefore be explored in appropriately selected groups of patients.

Antigens, Neoplasm↗

PubMed2002

Cytotoxic T-cell induction in metastatic melanoma patients undergoing recombinant vaccinia virus-based immuno-gene therapy.

In an ongoing phase I/II study, metastatic melanoma patients were treated with a replication-incompetent recombinant vaccinia virus (rVV) encoding Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) HLA-A*201-restricted epitopes together with B7.1 and B7.2 co-stimulatory molecules. rVV was administered in the context of systemic GM-CSF treatment. Boosts were subsequently administered 2 weeks apart with corresponding synthetic nonapeptides and GM-CSF. Two cycles of treatment were administered 2 weeks apart from each other. Specific immune responses were evaluated by quantitative assessment of cytotoxic T-lymphocyte precursor frequency and tetramer staining. By the time the two cycles had been completed, four out of five patients showed significant (greater than threefold) increases in gp100(280-288)-specific and four out of five, in Melan-A(27-35)-specific tetramer staining of CD8+ cells. Frequencies of CTL precursors specific for gp100(280-288), tyrosinase(1-9) and Melan-A(27-35) were also significantly increased in all five, and in four and four of the five patients, respectively, in some cases within 12 days after the first injection of the recombinant vector. Thus, the innovative vector under investigation is able to raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells displaying heterogeneous antigen expression.

Epitopes↗

PubMed2002

Nonoperative treatment of splenic rupture in malaria tropica: review of literature and case report.

In many parts of the world malaria still is a major medical problem. Heavy international and transcontinental traveling carries malaria to non-endemic areas. Practicing physicians must be aware of the common, but also the rare and severe complications of malaria. During malaria changes in splenic structure can result in asymptomatic enlargement or complications such as hematoma formation, rupture, hypersplenism, ectopic spleen, torsion, or cyst formation. An abnormal immunological response may result in massive splenic enlargement. Spontaneous rupture of the spleen is an important and life threatening complication of Plasmodium vivax infection, but is rarely seen in Plasmodium falciparum malaria. The ability to properly diagnose and manage these complications is important. Spleen-conserving procedures should be the standard whenever possible especially in patients with a high likelihood of future exposure to malaria.

Adult↗

PubMed2002

Association between bone loss in periodontal disease and polymorphism of N-acetyltransferase (NAT2).

BACKGROUND: The individual susceptibility to periodontal disease is probably the result of an interaction of multiple genetic and environmental influences. Polymorphism of the N-acetyltransferase (NAT 2) modifies the individual susceptibility to toxicity from certain therapeutic drugs or heterocyclic amines including substances from cigarette smoke. Subjects are to be classified as 'slow' or 'rapid' acetylators according to how fast their bodies metabolise such xenobiotics. Differences in their ability to detoxify these substances may contribute to an increased risk for periodontitis in subjects exposed to cigarette smoke or other xenobiotics. OBJECTIVE: The purpose of this study was to assess whether the NAT2 genotype is a risk factor for periodontal disease in Caucasian patients suffering from adult periodontitis. MATERIAL AND METHODS: 154 Caucasian subjects were assigned to one of the 3 groups: no, moderate, and severe periodontal disease based on bone and attachment loss. In all subjects, genotyping for mutations on the N-acetyltransferase (NAT2) gene was performed by means of PCR and RFLP analysis. RESULTS: Comparison of frequency distribution of NAT2 acetylation types between the most diseased group and not or moderately affected subjects showed a tendency to over-representation of slow acetylators with severe disease. When using bone loss as measure of periodontitis, this over-representation shows a significant association with the disease (odds ratio=2.13, p=0.025). In the logistic regression analysis, adjusted for age and smoking, NAT2 slow phenotype was significantly associated with the severity of bone loss, the odds ratio being 2.09 (95% C.I. 1.02-4.26, p=0.043). In a case-control analysis (controlled for smoking, gender and age) mean bone loss showed a significant difference between the 2 NAT2-type groups (Mann-Whitney test p=0.041). CONCLUSION: The data suggest that the slow acetylator phenotype may be associated with a higher risk of periodontitis, especially in smokers. Possible explanations regarding the mechanism are discussed; however, such attempts are highly speculative at this time.

Adult↗

PubMed2002

Anti-plaque effect of tempered 0.2% chlorhexidine rinse: an in vivo study.

OBJECTIVES: The aim of this in vivo study was to compare the anti-plaque effect of warm and cold chlorhexidine gluconate irrigation on matured human plaque. METHODS: In a split-mouth design, the antibacterial effect of 47 degrees C "warm" 0.2% chlorhexidine solution was compared with that of 18 degrees C "cold" rinse at the same concentration on newly-formed supragingival plaque that had been left undisturbed for 72 h. Before and 1 h after a 1-min rinse procedure, plaque was sampled from 10 test persons and vitality determined using vital fluorescence technique. RESULTS: Cold and warm 0.2% chlorhexidine solution reduced plaque vitality significantly from 99.63% to 77.81% (p=0.014) and from 98.98% to 51.77% (p<0.001), respectively. Rinsing with warm chlorhexidine solution reduced plaque vitality to a significantly greater degree (p=0.003) than did cold chlorhexidine. CONCLUSION: In this study, warm 0.2% chlorhexidine rinse showed a significantly more intensive anti-plaque effect than cold chlorhexidine solution at the same concentration.

Adult↗

PubMed2002

Periodontal attachment level of extractions presumably performed for periodontal reasons.

BACKGROUND/AIMS: The aim of this study was to analyse the residual periodontal attachment in teeth extracted by East German dentists in order to determine a possible 'forceps level'. METHODS: Out of about 8000 extracted teeth collected from a dental waste disposal company, 500 teeth were randomly selected. After exclusion of wisdom teeth and premolars extracted for orthodontic reasons (intact teeth with attachment > 90%), coronal and root caries, fillings, pulp exposure and incomplete root fillings (based on X-rays) were registered. The periodontal ligament was stained with 1% Fuchsin Red and measured with a light microscope. RESULTS: For intact teeth (DF = 0, periodontal disease definition I), the mean periodontal attachment (50.5% +/- 16.0) was significantly lower than for teeth with carious defects or fillings (64.7% +/- 18.8. unpaired t-test: p < 0. 00 1). There was a marked increase in frequency of extractions in intact teeth below 70% periodontal attachment and 37% were extracted at attachment levels between 50 and 69%. Teeth with pulpal involvement showed significantly different frequency distributions and mean attachment values (77.9% +/- 17.8) than the remaining teeth (periodontal disease definition II; 55,2% +/- 15.5). CONCLUSIONS: A considerable number of teeth with no or minor coronal destruction were extracted at an attachment level of 50-70%, regardless of the tooth type. The threshold for 'periodontal' extractions seem to be too low and undifferentiated, which calls for an improvement in knowledge of periodontal diagnosis and treatment.

Dental Caries↗

PubMed2002

The effect of a SCN-/H2O2 toothpaste compared to a commercially available triclosan-containing toothpaste on oral hygiene and gingival health -- a 6-month home-use study.

OBJECTIVES: The aim of the study was to compare the gingival health benefits of a thiocyanate/carbamide peroxide toothpaste to that of a triclosan toothpaste in home use. MATERIALS AND METHODS: The study was a two-centre, randomised, double-blind, parallel-group clinical trial, and consisted of a 2-week pre-experimental phase, followed by an experimental period of 6 months. A total of 140 healthy male and female volunteers (70 per group) who had at least 20 natural teeth with no probing depths greater than 5 mm and a mean gingival index (GI) of 1 or more at screening were admitted to the study. The two products were the test toothpaste (RCP) containing 0.5% SCN- (rhodanide), carbamide peroxide (equivalent 0.1% H2O2), and 1450 p.p.m. fluoride, and a control toothpaste (Colgate Total) containing 0.3% triclosan, 2.0% polyvinyl methyl ether maleic acid (PVM/MA), and 1450 p.p.m. fluoride (Triclosan). In the pre-experimental phase, all subjects used a fluoride toothpaste. Plaque (Turesky et al. 1970) and gingivitis (Löe & Silness 1963) were scored prior to beginning the pre-experimental phase, at baseline, and after 6 weeks and 3 and 6 months. RESULTS: In both the RCP and the Triclosan group, gingival health improved significantly between baseline and the following examinations. Plaque scores decreased significantly between baseline and 6 months in both groups. There were, however, no significant differences between the groups for either gingival index or plaque index. CONCLUSION: To conclude, this study seems to verify that in normal home use, a toothpaste containing a combination of thiocyanate and carbamide peroxide is as effective in reducing gingival inflammation and supragingival plaque formation as a benchmark control product.

Adult↗

PubMed2002

Tooth loss and pocket probing depths in compliant periodontally treated patients: a retrospective analysis.

BACKGROUND/AIMS: This retrospective study determined the treatment outcomes of 142 compliant periodontal patients observed for at least 10 years at the University of Kiel. All patients had been treated for moderate to advanced periodontitis and regularly received supportive periodontal therapy (SPT). METHODS: Patient- and tooth-related variables [tooth loss and pocket probing depth (PPD)] were analysed. RESULTS: Of a total of 3353 teeth, 167 were extracted during active treatment and 99 during SPT, mainly for periodontal reasons. Forty-five per cent of the patients did not lose any teeth during 11.7 years of observation. Thirty-seven per cent underwent extractions during active treatment or SPT, 18% both during active periodontal therapy and SPT. Mean tooth loss per patient was 0.07 teeth/year during SPT. Mobility, furcation involvement, smoking, and prescription antibiotics had a negative impact on prognosis. Intraindividual differences in PPD were significant between single- and multirooted teeth with initial PPD > or = 4 mm at baseline, following active treatment and at the end of SPT, and between firm and mobile teeth at baseline. Interindividual differences in mean PPD were only significant between smokers and non-smokers at the end of the observation period. CONCLUSIONS: Long-term maintenance of our patients was effective. Periodontal disease represented the major cause of tooth loss in a minority of the population.

Adult↗

PubMed2002

Methodology of three-dimensional determination of root surface roughness.

In comparing and evaluating the instruments that are used in root debridement, roughness constitutes a standard variable that is assessed. The purpose of this study was to describe the conditions and requirements for the three-dimensional roughness measurements of tooth roots using a laser profilometer. Impressions were made of 60 instrumented and 12 untreated root surfaces, which were then measured using a dynamically focussing optical profilometer (Mikrofocus, UBM, Karlsruhe, Germany). To separate roughness from the form of the tooth, a low pass filter was applied. This meant that the longer wavelengths - which roughly approximated the root forms - were subtracted from the measured profile. We then used an individualized Fourier transformation to define the threshold at which roughness becomes waviness. Roughness parameters were Ra (average roughness) and Rz (average roughness in the z dimension) for two- and three-dimensional measurements. To describe the requirements for the measurement, we studied the effect of pixel density and the field size on the average roughness value, Ra. We found that Ra increases with pixel density until 400 per mm is reached, after which it does not change meaningfully. Furthermore, Ra is highly dependent upon the area of the field to be scanned, increasing in line with the area, and does not approach one value within the surface available on one tooth. The correlation coefficients between the two-dimensional and three-dimensional Ra and Rz values ranged from 0.7 to 0.8. We conclude that roughness values are strongly dependent on the measurement conditions and the results of one study cannot be directly compared to another. In addition, it was found that two-dimensional measurements are sufficient for characterizing root surfaces.

Dental Scaling↗

PubMed2002

Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma.

OBJECTIVE: To evaluate MAGE tumor-associated antigen (TAA) expression in an extensive panel of normal and neoplastic tissues. SUMMARY BACKGROUND DATA: TAAs of the MAGE family represent targets of active specific immunotherapy. Limited-size studies indicate that they are expressed in normal testis and tumors of different histologies. High-throughput tissue microarray (TMA) technology and MAGE TAA-specific monoclonal antibodies now allow us to comprehensively evaluate their expression in large numbers of tissues and to address clinical correlations. METHODS: A TMA containing 3,520 samples from 197 different tissues and a non-small-cell lung cancer TMA including 301 specimens were stained using the MAGE TAA-specific monoclonal antibody 57B. For patients with squamous cell carcinoma of the lung, the dichotomous result (positive vs. negative) of MAGE TAA staining was used as a predictor variable along with other covariates in proportional hazard regression analysis of tumor-specific survival. RESULTS: MAGE TAAs are expressed with frequencies ranging between 22.7% (larynx) and 50% of cases (lung) in squamous cell carcinomas from different anatomic areas and in large cell carcinomas of the lung (37.9%). The authors provide here the first description of MAGE TAA expression in basalioma (48.1%). To investigate the clinical significance of MAGE expression in a frequently positive tumor type, a non-small-cell lung cancer, TMA was then studied. In this TMA 43.2% of tumors were 57B positive. In patients with squamous cell carcinoma, MAGE TAA positivity was significantly correlated with a shorter tumor-specific survival in the proportional hazard regression analysis model. CONCLUSIONS: These data suggest novel potential therapeutic indications in different types of cancers. In lung squamous cell carcinoma, the significant association of MAGE TAA expression with poor prognosis suggests that patients with 57B-positive tumors may benefit from early, specific immunotherapy procedures.

Adult↗

PubMedDate not supplied

Study of Health in Pomerania (SHIP): Relationship among socioeconomic and general health factors and dental status among elderly adults in Pomerania.

OBJECTIVE: The aim of this study was to evaluate associations among the dental status, socioeconomic factors, and general health of 1,877 subjects between the ages of 55 and 79. METHOD AND MATERIALS: Socioeconomic information (age, sex, education level) and questions on smoking and alcohol abuse were taken from an interview; income and medical information (number of diseases) were taken from a self-administered questionnaire; and HbA1C and CDT (diabetes and alcoholism markers) were taken from blood analyses. RESULTS: Of the subjects, 73% had a low education level, and 27% of the subjects had a monthly income of < 1,000 Euro and 13% of > 2,000 Euro. Twenty-six percent of the subjects were edentulous, and 29% had 20 or more teeth. The odds ratio of edentulism increased to 9.0 (95% confidence interval = 7.0-11.5) at the ages of 75 to 79 years compared to ages 55 to 79. Logistic regression analyses showed that edentulism was significantly associated with age, low education level, low income, smoking, and alcohol abuse. However, the retention of more than 20 teeth was associated with age. CONCLUSIONS: Age, low income, low education level, smoking, and alcohol abuse seemed to be risk markers for edentulism; whereas, the number of diseases, diabetes, and gender were not.

Age Distribution↗

PubMedDate not supplied

Risk factors for high occlusal wear scores in a population-based sample: results of the Study of Health in Pomerania (SHIP).

PURPOSE: Using a population-based sample of the cross-sectional epidemiologic "Study of Health in Pomerania" (SHIP), this study evaluated whether certain occlusal and sociodemographic factors besides age and gender are risk factors for high dental wear. MATERIALS AND METHODS: Medical history and dental and sociodemographic parameters of 2,529 dentate subjects selected representatively and according to age distribution were checked for correlations with the occurrence of high occlusal wear symptoms using a multivariate logistic regression model. Occlusal wear was recorded using the attrition index by Ekfeldt et al and was age adjusted by determining high occlusal wear for every 10-year age group as index values > or = 90th percentile. RESULTS: The following independent variables were found to be correlated with high occlusal wear: male gender, odds ratio 2.2; frequent bruxism, odds ratio 2.5; loss of molar occlusal contact (Eichner classification), odds ratio from 1.5 to 3.1; edge-to-edge relation of incisors, odds ratio 1.7; unilateral buccolingual cusp-to-cusp relation, odds ratio 1.8; and unemployment, odds ratio 1.6. In contrast, anterior cross-bite, unilateral posterior cross-bite, and anterior crowding were protective for high occlusal wear levels, as shown by significantly reduced odds ratios. Gender-separated analysis showed that self-reported bruxism was a risk factor only for men. CONCLUSION: In addition to some occlusal factors, the main factors associated with occlusal wear were bruxism and gender.

Adult↗

PubMedDate not supplied

Gender differences in associations between occlusal support and signs of temporomandibular disorders: results of the population-based Study of Health in Pomerania (SHIP).

PURPOSE: The aim of this study was to investigate whether gender-dependent associations exist between signs of temporomandibular disorders (TMD) and occlusal support. MATERIALS AND METHODS: Stratified by gender, the data of 2,963 35- to 74-year-old participants from the epidemiologic Study of Health in Pomerania were used in logistic regression analyses with temporomandibular joint (TMJ) tenderness and muscle tenderness as the dependent variables. Occlusal support was classified according to the Eichner index, a classification system based on occluding pairs of teeth. The final model was adjusted for bruxism, age, and various sociodemographic data. RESULTS: Logistic regression analyses revealed increased odds ratios for TMJ tenderness in men with loss of all four molar and premolar supporting zones (odds ratio 3:9) and without antagonist contact (odds ratio 2:7). Significant relationships in men were also found between muscle tenderness and loss of one (odds ratio 2:1), three (odds ratio 2:1), or four supporting zones (odds ratio 2:7), and loss of any tooth contact (odds ratio 2:3). In women, significant associations between occlusal support and TMD signs were absent. Subjects with bruxism were more likely to have TMJ tenderness (odds ratio women 2:0, men 1:9). In women, an additional relationship existed between bruxism and muscle tenderness (odds ratio 1:7). The following habits showed no significance: gum chewing, unilateral chewing, and lip/tongue/cheek biting. CONCLUSION: Only in men was the loss of occlusal support significantly associated with muscle and TMJ tenderness. The association between bruxism and TMD signs supports the theory that repetitive adverse loading of the masticatory system may cause functional disturbances.

Adult↗