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Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 37 records · Page 2Linked to original sources

A dietary pattern protective against type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam Study cohort.

AIMS/HYPOTHESIS: The aim of this study was to identify a dietary pattern associated with diabetes-related biomarkers and to investigate whether this pattern is associated with the incidence of type 2 diabetes. METHODS: A nested case-control study of 192 cases of incident type 2 diabetes and 382 control subjects matched for sex and age was conducted. All subjects were participants in the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Dietary pattern score was derived using intake data on 48 food groups as exposure variables and the biomarkers HbA1c, HDL cholesterol, C-reactive protein and adiponectin as response variables in reduced rank regression. The association of the score with diabetes risk was estimated by conditional logistic regression analysis. RESULTS: A high score for the identified dietary pattern was characterised by a high intake of fresh fruit and a low intake of high-caloric soft drinks, beer, red meat, poultry, processed meat, legumes and bread (excluding wholegrain bread). Subjects with high scores had high plasma concentrations of HDL cholesterol and adiponectin and low plasma concentrations of HbA1c and C-reactive protein. After multivariate adjustment, the odds ratios for type 2 diabetes across increasing quintiles of the dietary pattern score were 1.0, 0.59, 0.51, 0.26 and 0.27, respectively (p = 0.0006 for trend). CONCLUSIONS/INTERPRETATION: A high score for the identified dietary pattern is associated with a more favourable biomarker profile and a substantially reduced incidence of type 2 diabetes.

Adiponectin↗

Escobar variant with pursed mouth, creased tongue, ophthalmologic features, and scoliosis in 6 children from Oman.

We report on six Omani children from two consanguineous families, with a multiple congenital anomaly syndrome defined by arthrogryposis multiplex congenita, typical facial appearance, ophthalmologic anomalies, atrophic calf muscles, and interdigital, neck and axillar pterygia. In addition, the patients present unique features as a furrowed tongue and enlarged corneal nerves, undescribed previously in association with other distal arhtrogryposis syndromes (DA). The patients can be classified as multiple pterygium syndrome (Escobar syndrome) but display overlapping features with Freeman-Sheldon syndrome and arthrogryposis with ophthalmologic abnormalities. We excluded two known arthrogryposis loci on chromosome 9p13 (TPM2) and 11p15 (TNNI2, TNNT3). We conclude that our patients display a subtype of multiple pterygium syndrome with overlapping features to other DAs.

Abnormalities, Multiple↗

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Adenocarcinoma↗

How to improve quality assurance in fluorometry: fluorescence-inherent sources of error and suited fluorescence standards.

The scope of this paper is to illustrate the need for an improved quality assurance in fluorometry. For this purpose, instrumental sources of error and their influences on the reliability and comparability of fluorescence data are highlighted for frequently used photoluminescence techniques ranging from conventional macro- and microfluorometry over fluorescence microscopy and flow cytometry to microarray technology as well as in vivo fluorescence imaging. Particularly, the need for and requirements on fluorescence standards for the characterization and performance validation of fluorescence instruments, to enhance the comparability of fluorescence data, and to enable quantitative fluorescence analysis are discussed. Special emphasis is dedicated to spectral fluorescence standards and fluorescence intensity standards.

Journal Article↗

UVA1 and UVB irradiated skin investigated by optical coherence tomography in vivo: a preliminary study.

In histological studies, it has frequently been demonstrated that ultraviolet (UV) exposure, in particular UVB, can induce significant thickening of the viable epidermis and/or stratum corneum. Since skin biopsy alters the original skin morphology and always requires an iatrogenic trauma, we aimed to introduce optical coherence tomography (OCT) in vivo for the investigation of changes of epidermal thickness (ET) following UVA1 and UVB irradiation. Twelve healthy subjects received daily 60 J/cm2 of UVA1 and 1.5 minimal erythema doses UVB on their upper back over 3 consecutive days. Twenty-four hours after the last irradiation, OCT assessments were performed on UV exposed and adjacent nonirradiated control sites. Data of ET as expressed by comparison of the averaged A-scans differed significantly between nonirradiated (94.2 +/- 15.7 microm), UVA1 (105.4 +/- 12.8 microm) and UVB (125.7 +/- 22.1 microm) exposed sites. In comparison to the nonirradiated sites, UVA1 exposed skin showed significant (P = 0.022) increase of ET of 11% and UVB exposed sites a significant (P < 0.001) increase of 25%. ET of UVA1 and UVB exposed skin sites differed significantly (P =0.005). Our results obtained from OCT in vivo measurements confirm data of previous histological studies indicating that not only erythemogenic doses of UVB, but also suberythemogenic doses of UVA1 may have a significant impact on ET. OCT appears to be a promising bioengineering technique for photobiological studies. However, further studies are needed to establish its measurement precision and validity, and to investigate in vivo spectral dependence on UV induced skin changes such as skin thickening.

Adult↗

easyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses.

UNLABELLED: We have generated the program easyLINKAGE that combines automated setup and performance of linkage analyses and simulation under an easy to handle graphical user interface for Microsoft Windows 2000/XP and standard UNIX systems. The program package supports two-point linkage analyses (FastLink v4.1 and SPLink v1.09), multi-point linkage analyses [GENEHUNTER v2.1, GENEHUNTER-PLUS with the emendation by Kong and Cox v1.2 (allele sharing modelling)] and the simulation package SLINK v2.65, and provides genome-wide as well as chromosomal postscript plots of LOD scores, NPL scores, P-values and other parameters. AVAILABILITY: http://www.uni-wuerzburg.de/nephrologie/molecular_genetics/molecular_genetics.htm SUPPLEMENTARY INFORMATION: Supplementary information is available on the website.

Chromosome Mapping↗

[Entrapment-syndrome of the popliteal artery: morphological and functional diagnosis using MRT inclusive provocation test].

A 30-year old man with pain in the right calf was submitted. Typical cardiovascular risk factors were excluded. Contrast enhanced MR-angiography at rest showed occlusion of right popliteal artery with collateral vessels due to an abnormal origin of medial head of gastrocnemius muscle at femoral diaphysis. In contrast to a normal MR-angiography at rest the exercise test detected a lateral deviation and a severe functional stenosis of the left popliteal artery. This was caused by an abnormal medial origin of medial head of gastrocnemius muscle at the inner femoral condylus. The patient has been treated with vascular reconstruction combined with myectomy on the right side and with myectomy only on the left side. These findings showed two different types of popliteal artery entrapment syndrome in one patient. MRI is able to detect the different types especially in different stages. Irreversible damages of popliteal artery in early diagnosed stages may thereby be prevented.

Adult↗

Effects of repeated sunbed exposures on the human skin. In vivo measurements with confocal microscopy.

BACKGROUND: Ultraviolet (UV) lamps used in commercial sunbeds are usually defined as UVA sources. Although it is well accepted that sunbed exposure significantly increases melanin pigmentation, its capacity to induce epidermal thickening is discussed controversially. OBJECTIVES: The aim of this study was to assess non-invasively the effects of repeated sunbed exposures on epidermal thickness, cell size, and pigmentation by means of confocal laser-scanning microscopy (CLSM) in vivo. METHODS: Eight volunteers had sunbed exposures six times in a 3-week period (cumulative dose: 126 J/cm(2) UVA). During irradiation, a small site (2 cm x 2 cm) on the lateral aspect of the inner forearm was covered with a UV-opaque sheet (non-exposed site). CLSM was performed with the Vivascope (Lucid, Henrietta, NY, USA) 24 h after the last UVA exposure on non-exposed sites and UVA-exposed sites that were on the medial aspect of the inner forearm at a distance of 2 cm to the non-exposed measurement site. The following parameters were assessed: thickness of the horny layer (DSC), minimal thickness of the epidermis (E(min)), minimal thickness of the viable epidermis (VE(min)), cell size of the granular layer (A(gran)), and the epidermal melanin content (MI). Additionally, colorimetric measurements have been carried out on non-exposed and UVA-exposed sites. RESULTS: DSC of the UVA-exposed skin was significantly higher than the one of non-exposed sites (mean+/-SD: 15+/-2.9 microm vs. 12.8+/-3 microm). Although E(min) was significantly higher in UVA-exposed sites (mean+/-SD: 40.4+/-3.6 microm vs. 39+/-2.9 microm), a slight but not statistically significant (P>0.05) decrease of VE(min) was observed (25.5+/-2.1 microm vs. 26.2+/-2.4 microm). The median of cell size of the granular layer (A(gran)) significantly (P=0.008) differed between non-exposed (752.1 microm(2)) and UVA-exposed sites (600 microm(2)). MI was significantly (P=0.014) higher for the UVA-exposed skin (1.12 vs. 1.34). Accordingly, colorimetry revealed significantly (P< 0.01) lower skin brightness for UVA-exposed sites (L*=60.2+/-4.3) as compared with non-exposed sites (L*=63.4+/-3.9). CONCLUSIONS: Sunbed exposures seem to induce photoadaptation not only by skin pigmentation but also by epidermal thickening that is predominantly due to an increase in thickness of the horny layer. Moreover, our data indicate that UVA radiation has an influence on the cell size of the granular layer. CLSM is a promising tool for photobiological studies in vivo.

Adaptation, Physiological↗

Histomorphologic correlation with routine histology and optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a new and promising diagnostic technique for investigation of skin tumours. We describe a method that makes evaluation and definition of specific morphologic structures of skin tumours via OCT more accurate. MATERIALS AND METHOD: We investigated three patients with basal cell carcinoma and three patients with melanocytic nevi. Three-dimensional (3D) images were obtained from these skin tumours via OCT according to previously applied marks, which were tattooed with special histological marking dye after excision of the tumours. Corresponding to these marks, we investigated serial histological sections (haematoxylin&eosin staining). RESULTS: We could prove similar morphological structures both in OCT and histology. Due to tissue deformation, the compared measurements of structures like cell nests or epidermal thickness were slightly deviated. However, by this method we could prove similar tissue formations in OCT and histology. CONCLUSIONS: Due to the deformation by histological processing and slightly different sectioning levels, the comparison of histological pictures and OCT images seems difficult. Nevertheless, in two cases it was possible to demonstrate the same morphological structures with OCT imaging and histological investigation. Our method could play an important role for further evaluation of OCT images. We estimate better evaluation of OCT imaging using a 3D reconstruction method.

Basal Cell Carcinoma↗

A comprehensive index for the modeling of smoking history in periodontal research.

Cigarette smoking is both a strong and common risk factor for chronic periodontitis. It is a multi-dimensional exposure that is difficult to model accurately. We propose a new comprehensive smoking index (CSI) that accounts for intensity, duration, and recency of smoking and allows for estimation of the half-life of the smoking effect. Using NHANES III data from 12,623 subjects aged 20+ yrs, we compared the performance of the CSI with that of various conventional approaches using multiple logistic regression models of chronic periodontitis. The estimate of the smoking effect's half-life was 1.5 yrs (95% CI, 0.5-2.5 yrs). Use of the new index resulted in best model fit and the highest Wald statistic for the smoking effect on chronic periodontitis. The results suggest that use of the CSI may be a more comprehensive, efficient, and parsimonious approach to the modeling of smoking history in periodontal research.

Adult↗

Effects of localized cutaneous vascular alteration on reactive hyperemia.

BACKGROUND: Cutaneous microcirculation shows a distinctive spatiotemporal inhomogeneity. Therefore provocation tests are necessary to receive significant and reproducible data. The present study investigated the effect of localized cutaneous vascular alteration, like in psoriasis vulgaris, on different parameters of reactive hyperemia (peak capillary blood cell velocity [pCBV], postocclusive reactive hyperemia [PRH%], and time to peak capillary blood cell velocity [tpCBV]). MATERIAL AND METHODS: Psoriatic plaques and normal skin on the contralateral side of 20 patients with psoriasis vulgaris were examined by Laser Doppler Anemometry. Capillary blood cell velocity was measured before suprasystolic occlusion and during postocclusive hyperemia. RESULTS: Compared to normal skin psoriatic plaques showed a significant increase of peak capillary blood cell velocity (pCBV, normal skin: 0.89+/-0.23 mm/s, psoriatic plaque: 2.03+/-0.94 mm/s), resting capillary blood cell velocity (rCBV, normal skin: 0.43+/-0.12 mm/s psoriatic plaque: 0.72+/-0.20 mm/s) and postocclusive reactive hyperemia (PRH%, normal skin: 107%, psoriatic plaque: 180%). The time to peak capillary blood cell velocity (tpCBV) during reactive hyperemia did not change significantly. CONCLUSION: In reactive hyperemia, changing of pCBV and PRH% combined with unaltered tCBV indicate a dysfunction of cutaneous microcirculation. In contrast acute closure of upper and lower arterial extremity show a changed tCBV with stable pCBV and PRH%.

Blood Flow Velocity↗

[Noninvasive diagnosis of skin functions].

Noninvasive investigation of skin functions is increasingly employed in dermatology and cosmetology. It enables one to study aspects of skin functions that cannot always be appreciated by sensory perception. Noninvasive methods permit objective and reproducible investigation of distinct biophysical parameters. In the age of evidence-based medicine this becomes more and more important. Biophysical data can be quantified, analyzed, and stored electronically. In an overview, selected noninvasive techniques of skin function testing are introduced and their relevance in dermatology, dermatopharmacology, and cosmetology is discussed.

Aged↗

Rapid genotyping of MBL2 gene mutations using real-time PCR with fluorescent hybridisation probes.

In this study, we describe a real-time polymerase chain reaction (PCR) for genotyping all known polymorphisms of the human mannose-binding lectin 2 (MBL2) gene. These comprised two variations in the 5' regulatory region at positions -550 (H/L) and -221 (X/Y), one in the 5' untranslated sequence at position +4 (P/Q) and three structural mutations within exon 1 at codons 52, 54, and 57, also known as the D, B and C variants, respectively. Three reactions with two different conditions were sufficient to genotype one individual unambiguously. The three mutations in exon 1 were detected in one capillary using a sensor probe covering the three mutations, whereas amplification of the variants located upstream of the coding sequence was performed in only two reactions. Single colour detection was used for detection of the (H/L) polymorphism and multiplexing by dual colour probes was used for simultaneous genotyping of (X/Y) and (P/Q). The reliability of the system was evaluated by comparison with a conventional PCR method with sequence-specific primers (PCR-SSP). For this study, 100 individuals of Danish and 30 of African descent were analysed, and the genotypes obtained were concordant in all cases. This new method is rapid and provides reliable results without ambiguities.

DNA Mutational Analysis↗

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗

Mechanisms of apoptosis: UVA1-induced immediate and UVB-induced delayed apoptosis in human T cells in vitro.

OBJECTIVE: The decreased number of lymphocytes combined with the induction of apoptosis and necrosis seems to be the key mechanism of many phototherapeutic agents. The purpose of our study was to determine the regulating pathway, time course and dose dependence of UVA1- vs. UVB-induced cell death in human T lymphocytes. METHODS: In our study we applied an in vitro method using single-laser flow cytometry differentiating between intact (Annexin V-FITC-/PI-), apoptotic (Annexin V-FITC+/PI-) and necrotic T cells (Annexin V-FITC+/PI+) following UVA1 (340-400 nm) or UVB (280-320 nm) irradiation. Additionally, fluorescence microscopy of apoptotic cells was performed using acridine orange and ethidium bromide. RESULTS: Compared to DNA-binding fluorescent microscopy, the flow cytometric method revealed similar, but more precise, results concerning apoptosis and necrosis. Our data indicate that UVB irradiation exerts its effects by the induction of delayed apoptosis within 24-48 h. In contrast, UVA1 irradiation acts via the dose-dependent induction of immediate apoptosis and necrosis within 6 h. CONCLUSIONS: Our findings demonstrate that UVA1 irradiation may effect structural and functional modifications leading to immediate initiation of apoptosis followed by early membrane rupture, whereas UVB irradiation leads to DNA damage followed by delayed apoptosis, obviously without initial membrane alteration.

Adult↗

[Comparison of two measurement methods with a gold standard as applied to 20-MHz-sonography and clinical palpation for ascertaining the thickness of pigmented skin tumours].

AIM: This paper focuses on different statistical methods for comparing two measurement methods with an additionally available gold standard. A given data example is used as the basis of the calculations. METHOD: We provide a complementary statistical analysis of a study presented by Hoffmann et al. on sonometric and palpatory measurements of the size of pigmented skin tumours in 681 patients. RESULTS: For comparing two measurement methods with respect to a gold standard, several statistical parameters assessing one measurement method can be used. In addition, there are further descriptive and some inference-statistical methods available. CONCLUSION: If there is a suitable categorization of the measurements, the comparison of the methods should be performed using the positive predictive values and kappa coefficients as descriptive measures. Moreover, the McNemar test can be used for comparing the differential accuracy of allocation. When investigating continuous measurements, a comparison using mere correlation analyses can lead to false conclusions. Therefore, we recommend the direct analysis of the individual measurement errors by means of numerical and graphical representations. The absolute values of the measurement errors can be compared using the sign test for paired samples.

Biometry↗