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Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 217 records · Page 12Linked to original sources

[Imaging superficial skin tumors of the ENT area. High frequency ultrasound in comparison with computerized tomography and magnetic resonance tomography].

In order to improve the preoperative diagnosis of superficial skin tumors in the head and neck, 32 patients with 42 basal cell carcinomas, squamous cell carcinomas and malignant melanomas were investigated using different imaging techniques. All patients were examined preoperatively with high-frequency ultrasound (HFU), computed tomography (CT) and magnetic resonance imaging (MRI). New high-frequency ultrasonic scanners (15- and 20-MHz) having an axial resolution of 50-90 microns permit visualization of dermal and cartilaginous structures with an anatomical accuracy to a range of 15 mm in tissue. Exact measurement of the skin tumors and their relation to adjacent structures was feasible. Histologically different tumors could be discriminated by their echo-structure in 80% of the cases. CT and MRI provided additional information when the tumor extension perpendicular to the skin exceeded 15 mm. If tumor extension was less than 15 mm, CT and MRI were inferior to high-frequency ultrasound in the diagnosis of superficial skin tumors and did not provide any additional information. The experience reported has shown that high-frequency ultrasound is a valuable tool for preoperative evaluation of superficial skin tumors in terms of tumor extension and possible invasion of functionally and esthetically important adjacent structures. This knowledge can support preoperative planning of possible resections as well as reconstruction and may help to obtain an appropriate informed consent.

Adult↗

Crystallization and X-ray diffraction study of the Streptomyces K15 penicillin-binding DD-transpeptidase.

The 262 amino acid residue long DD-transpeptidase/penicillin-binding protein of Streptomyces K15 has been crystallized at room temperature by using the hanging drop vapour diffusion technique. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell parameters a = 46.4 A, b = 54.1 A and c = 108.3 A. They contain one protein molecule per asymmetric unit and diffract to about 1.9 A. X-ray data have been collected to 2.0 A from a native crystal. The previously published amino acid sequence of the protein has been corrected at positions 71, 72, 113, 114 and 156.

Bacterial Proteins↗

Purification and characterization of eucaryotic alanine racemase acting as key enzyme in cyclosporin biosynthesis.

A specific alanine racemase, which is a key enzyme in the biosynthesis of the undecapeptide cyclosporin A, was purified to electrophoretic homogeneity from the fungus Tolypocladium niveum. This is the first enzyme of this kind isolated from a eucaryotic organism. The enzyme catalyzes the reversible racemization of alanine and requires pyridoxal phosphate as the exclusive cofactor. Km values for L- and D-alanine were found to be 38 and 2 mM, respectively. Maximal reaction velocity was observed at 42 degrees C and pH 8.8 for the L to D direction. Molecular mass determinations of the denatured enzyme by SDS-polyacrylamide gel electrophoresis gave a value of 37 kDa, whereas gel filtration calibration studies yielded a value between 120 and 150 kDa, indicating an oligomeric native structure.

Alanine Racemase↗

Long-term manometry of tubular esophagus in progressive systemic sclerosis.

Long-term manometry of the tubular esophagus was performed in 20 consecutive patients (18 females, 2 males; median age 56.5 years) with progressive systemic sclerosis (PSS) and a control group of 20 healthy subjects (18 females, 2 males; median age 56.5 years). The measurements were performed via a data logger of 1 MByte memory capacity with the help of two pressure sensors placed 8 and 18 cm above the lower esophageal sphincter. Esophageal contractions were analyzed with respect to pressure amplitudes in the esophagus distal and proximal, quotient of pressure amplitudes distal/proximal, number of contraction waves in a 24-h period, and kind of spreading (propulsive, simultaneous). In the PSS group there was a significant decrease in pressure amplitudes in the distal sensor (median 31.5 versus 39.5 mbar in controls, P < 0.02), in the quotient of pressure amplitudes distal/proximal (median 0.885 versus 1.25 in controls, P < 0.001), in the number of waves in 24 h (median 939.5 versus 1656 in controls, P < 0.01), and in the occurrence of propulsive waves (median 34% versus 57% in controls, P < 0.01). Fifteen patients (75%) had hypomotility disorders as compared to the control group, in which the lower limit of normal values was defined by the 5th percentile of descriptive analysis. These first data of long-term manometry in patients with PSS indicate that long-term manometry may be an effective method for identifying esophageal involvement in PSS.

Adult↗

Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.

BACKGROUND: Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE: The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS: A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS: The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION: Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

Abdominal Pain↗

Laser Doppler imaging of axial and random pattern flaps in the maxillo-facial area. A preliminary report.

Objective, non-invasive examination, techniques in addition to clinical parameters, are required to follow-up the wound healing of flaps. With the new laser Doppler Scanner (LDI DIM 1.0 Lisca Development AB, Sweden) it is possible, for the first time, to measure and image the microcirculation continuously, non-invasively and without contact with the wound, in an area of 12 cm square maximum. We performed measurements and simultaneous two-dimensional imaging of the microcirculation 24, 48, 72 h and 5 and 14 days postoperatively in 20 patients, who had had reconstruction procedures performed using random or axial pattern flaps. The perfusion diagrams were correlated to the clinical appearance. Necrotic areas, venous stasis and normal course of wound healing can be clearly visualized and differentiated from one another. The new laser Doppler imaging system seems to be an excellent aid for following up and planning of flaps in plastic and reconstructive surgery.

Adolescent↗

[History of high frequency sonography].

The development of high frequency sonography (< 20MHz) has gained increasing importance since the last decade. In this field A-mode-scanner were used firstly in the measurement of skin thickness. 1987 the first commercial available 20 MHz B-scanning system was introduced. These systems provided the possibility of correlating the ultrasound images with the micromorphological findings in histology. With these correlations we were able to interpret ultrasound phenomena and in conclusion we were able to measure tumour thicknesses with direct impact on the therapeutic regimen. In inflammatory skin diseases the role of high frequency ultrasound in follow up investigations of morphea and systemic sclerosis must be underlined. We believe that in this field the technique is the "golden standard". In other inflammatory diseases (e.g. psoriasis) or wound healing ultrasound is mainly used for scientific purposes. The investigation of intraepidermal structures and differential diagnosis is only possible with higher frequencies than 20 MHz. Therefore we developed 50 and 100 MHz in vivo scanning systems. With resolution up to 11 microns (100 MHz) we hope to answer open questions in the future. Ultrasound microscopy is widely used for scientific evaluation of tissue morphology in vitro (resolution < 1 micron). Computer-based three-dimensional reconstructions provide additional information (e.g. tumour volume or tumour surface). These parameters are well suited to follow up the effect of systemic or local therapies on skin metastases of different cancers. However, also the tumour volume of the primary tumour (in vivo) might be of great interest as a prognostic parameter in future.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatitis↗

Sonographic quantification of the type IV reaction after intradermal application of recall antigens.

20-MHz B-scan high-resolution sonography permits non-invasive, two-dimensional visualisation of micromorphological structures in vivo, and allows precise measurement of the depth and extent of inflammatory skin lesions. In 50 patients, the reactions following intradermal application of 8 recall antigens to the volar forearm were evaluated clinically and sonographically at various times (0, 24, 48, 72 h). In 30 patients, one of the inflammatory papules was excised after 48 h for complete histological work-up (serial sections) and subsequent comparison with the sonographic image. Infiltrates were characterised in the ultrasound scans by the almost regular occurrence of convexity of the skin surface, by a loosened structure (loss of echogenicity) of the corium and by protrusion of the corium into the subcutaneous fatty tissue. It was also possible to follow the dynamics of the type IV reaction with the measurement of echogenicity (densitometry). High-frequency ultrasound is an objective, exact and very sensitive tool for the measurement of type IV reactions after intradermal application of recall antigens and therefore superior to clinical evaluation. The B-scan was superior to the A-scan. However, for routine evaluation of tuberculin-like reactions, sonography is too time-consuming. Our results suggest that densitometry provides no additional or necessary information compared to sonometry.

Adult↗

Evaluation of the efficacy of H1 blockers by noninvasive measurement techniques.

BACKGROUND: Evaluation techniques for determining the strength of action and the onset of activity of H1 receptor blockers have not yet been sufficiently standardized. OBJECTIVE: The clinical efficacy of the H1 receptor blocker loratadine was to be measured upon a wheal response subsequent to an intracutaneous injection of 0.1 ml histamine (0.1%). METHODS: In a pilot study, 10 patients were treated with the H1 receptor blocker loratadine for a period of 7 days. Various noninvasive measurement techniques, i.e. 20-MHz sonography, laser-Doppler flowmetry, chromatometry using the Lab* system and computer-assisted planimetry, were applied to provide a quantitative evaluation of the wheal and the marginal erythema. Using these quantification methods, the development of the urticarial reaction 20 min after injection and its decline were evaluated. RESULTS: The urticarial reaction was reduced substantially under treatment with 10 mg loratadine over a period of 7 days. The methods we used could accurately quantify different aspects of the urticarial reaction noninvasively. CONCLUSIONS: All of the chosen measurement techniques are widely recognized. For objective assessment of the urticarial reaction with high-frequency ultrasound, we recommend the measurement of the distance between skin entrance echo and fascia since the demarcation of the wheal is often impossible by ultrasound. In order to improve comparison of results of various workgroups in the future, we therefore suggest the use of the selected combination of noninvasive procedures as a standard for evaluating the efficacy of H1 receptor blockers.

Administration, Oral↗

Molecular and functional characterization of allergens: basic and practical aspects.

Well-defined allergen preparations are, in the first line, a prerequisite for exact diagnosis, but will be supposedly useful tools in immunotherapy of Type I (IgE-mediated) allergic diseases. The allergens have to be available in standardized and highly purified form in sufficient quantities. By applying recombinant DNA techniques this goal can be achieved with respect to both, characterization and reproducibility of allergen preparations. As an example, purified recombinant non-fusion Betv1 revealed identical immunological properties with respect to interaction with both, anti-Betv1 antibodies and Betv1-specific T cell clones when compared with natural Betv1 purified from birch pollen. Moreover, cloning of allergens yielded a number of deduced primary structures of allergens, which allows computer-aided comparisons with already known amino acid sequences. Significant sequence similarities with well-described proteins may point at a biological and biochemical function of the cloned allergen, which might be of interest for considerations why a certain protein within an extract represents an allergen. Furthermore, the interaction of small peptides synthesized according to amino acid sequences of cloned allergens with allergen-specific T and B cells can be investigated. Respective results will yield information about the regulation of IgE synthesis and, thus, might point at new concepts of immunotherapy.

Allergens↗

[Process markers of the indications and termination sessions in inpatient psychotherapy: indicators for treatment success?].

Within a comprehensive research project investigating the outcome and process of inpatient longterm group psychotherapy, the initial and final interviews with the individual patients were video-tape-recorded and analysed using the Vanderbilt Psychotherapy Scales. The ratings of the interviews were related to self descriptions of the patients at the beginning of their psychotherapy, to the patients' perception of the group process during therapy and to the outcomes. In addition the characteristics of the initial and the final interviews were compared with each other. The results indicate process characteristics of the individual interviews to be a useful perspective to thoroughly describe the process and outcome of inpatient psychotherapy.

Adolescent↗

Assessment of actinic skin damage by 20-MHz sonography.

Ninety people were evaluated on age-related changes of the dermal connective tissue in light-exposed and protected skin areas non-invasively by 20-MHz sonography. The method allows sonographic structures to be measured and densitometric values to be quantified in a region of interest. Sonography of sun-exposed skin regions shows an echo-poor band in the upper dermis, which corresponds to actinic elastosis in the histological picture. The band is sharply demarcated from the entry echo. The border towards the non-actinically altered dermis below is often serrated. The sonographic phenomena can be explained by the micromorphological changes that develop in the upper dermis in actinic elastosis. An increased amount of elastic material and the destruction of the fiber architecture as well as an increase in ground substance and a mild inflammatory reaction cause a reduction in echogenicity. The extent of elastotic alterations and their progression is expressed in the densitometric values. These are low in areas of high sun exposure (the forehead and the infraorbital region). The echogenicity of the echolucent band (ELB) diminishes with increasing age. In highly exposed regions we found the lowest densitometric values already in the 41- to 50-year-olds. However, the width of the ELB remains relatively constant, extending in all locations to the middle dermis. This finding differs from earlier publications. On the buttock skin as a nonexposed area, an ELB could only be found in 6.7% of the cases.

Adipose Tissue↗

Psoriasis vulgaris in 50 MHz B-scan ultrasound--characteristic features of stratum corneum, epidermis and dermis.

One hundred and forty fully developed, non-treated plaques of psoriasis vulgaris from the arms and legs of 22 patients were examined using 50 MHz B-scan ultrasound and compared with the images from adjacent, clinically normal skin. To visualize the dermis, high pre-amplification (digitization range 200 mV) was used, determined according to A-scan images. For evaluation of epidermal phenomena, low pre-amplification (digitization range 380 mV) was chosen in order to avoid overmodulation of the skin entry echo. In 10 patients, sonographic images were compared with histological sections from the exact same planes at the same magnification. At low pre-amplification, the skin entry echo is displayed as a markedly widened, frequently interrupted band composed of spots varying in thickness, height and echo density. Within these spots, several lamellae can be observed, represented as fine, echo-rich lines stacked one upon another. These phenomena correspond histologically to focal hyperparakeratosis, scaling and cracking of the stratum corneum. Due to the low amplification of the echo-signal the dermis is not visible. High pre-amplification allows evaluation of dermal changes. Below the entry echo there is an echopoor band (EPB) corresponding to the sum of acanthosis and infiltrate in the upper dermis. Underneath the EPB the dermis is represented as a zone with scattered internal echoes which are less intense than in normal skin. Dorsal shadows are typically present. They are artifacts emanating from epidermal regions with marked hyperkeratosis and disappear when the sonographic characteristics of the epidermis are changed, for instance by application of ointments prior to sonographic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The hyperperfusion of the psoriatic plaque correlates histologically with dilatation of vessels.

We examined psoriatic lesions on the upper legs in 20 patients, using a two-dimensional Laser-Doppler-Scanner (Laser Doppler Perfusion Imager LDI, Lisca Development, Linköping/Sweden). The plaques were evaluated weekly during therapy with dithranol. Five plaques were reconstructed three-dimensionally before and after therapy (reconstruction program ANAT 3D, SIS, Münster, Germany). The psoriatic plaque was represented in the Laser Doppler Perfusion image as a sharply demarcated, hyperperfused area. The perfusion of the plaques dropped during therapy with dithranol to just slightly increased values, compared with normal skin (2.04 arbitrary units AU, healthy skin 1.1 AU). Using three-dimensional reconstruction, we investigated the volume of dermal vessels and the density of papillae. When compared, the volume of papillary vessels was twice as large in psoriatic as in healthy skin. The number of the papillae per square millimetre, detected by three-dimensional reconstruction, was not reduced significantly during therapy. We think that the increased perfusion of the psoriatic plaque is due to the combination of morphological (dilatation of vessels), dynamic (increased blood flow) and optical effects (reduced scattering and increased sampling depth of the laser-beam in acanthotic tissue).

Anthralin↗

Multiple T cell specificities for Bet v I, the major birch pollen allergen, within single individuals. Studies using specific T cell clones and overlapping peptides.

Twenty-five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen-allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77-92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen-derived Bet v I, but neither with any peptide synthesized according to a Bet v I-encoding cDNA nor with the respective recombinant protein. Upon stimulation with allergen, the majority of the clones (21/24) revealed the TH0 or TH2 type of cytokine production (interleukin-4 production), indicating their importance in the pathogenesis of the allergic disease.

Allergens↗

Interferon-beta promoters contain a DNA element that acts as a position-independent silencer on the NF-kappa B site.

The human interferon-beta (IFN-beta) promoter contains several functional domains that contribute to its virus-inducible regulation. One of them, PRDII, and NF-kappa B-binding sequence, can function as a constitutively activating element. Due to the presence of a negative regulatory domain that mediates a constitutive repression the natural IFN-beta promoter is silent in the non-induced state. Within this domain we have delimited an 11 bp element that acts as a negative regulatory element (NRE) of PRDII. Although the NRE is physically overlapping with PRDII in the IFN-beta promoter, it acts as a position-independent silencer of PRDII. Virus infection, which leads to the transcriptional activation of the IFN-beta promoter, does not alter the negative activity of the NRE on an isolated PRDII. It is the cooperative effect of PRDI and PRDII that is able to overcome the NRE function after virus infection. By UV cross-linking analysis using uninduced and virus-induced nuclear extracts, we show that two factors with molecular masses of approximately 95 and 100 kDa bind to the NRE.

Base Sequence↗

A local education campaign on early diagnosis of malignant melanoma.

The growing incidence of all kinds of skin cancer is a worldwide phenomenon observed in the last decades. Malignant melanoma is of special concern because of its high death rate when in an advanced stage, poor therapeutic response and fast growing incidence. Malignant melanoma is primarily located on the skin and therefore well suited for early cancer detection. The "Deutsche Dermatologische Gesellschaft" carried out a highly successful information campaign in Germany. Under this roof we organised different campaigns. Following considerable success in a campaign in 1989, a total of 1467 patients were examined and advised in the course of a local initiative (Education Campaign "Black cancer") in the city of Bochum (approximately 400,000 inhabitants) in the summer of 1991. In addition to full body examinations, important data were collected concerning the degree of knowledge about skin cancer, epidemiology, and the risk of skin cancer in general. As a result of the clinical examinations, 73 patients with strongly suspected skin cancer have been treated. Within this group, 14 malignant melanomas (1.0%) as well as 34 basal cell carcinomas (1.9%) were diagnosed. These numbers highly exceed the assumed risk incidence of skin cancer in Germany. Even on the assumption that the population was selective it is to be feared that a high number of individuals with skin cancer remain undetected and untreated. The majority of persons seeking advice had been motivated by the local media. The response and results of this local campaign indicate that further preventive measures for the general population in Europe are conceivable, meaningful and urgently needed.

Adolescent↗

T cell clones specific for Bet v I, the major birch pollen allergen, crossreact with the major allergens of hazel, Cor a I, and alder, Aln g I.

Tree pollens are responsible for type I allergies during the flowering season in spring. Pollens from birch, hazel and alder constitute the most important allergen sources in this respect in the northern hemisphere. Human IgE antibodies, specific for the major allergens of these pollens, are known to crossreact, and in general every tree pollen allergic patient is sensitized to these three pollen allergens. In this study we investigated eight T-helper cell clones (CD3+, CD4+, TCR alpha/beta) with specificity for Bet v I, the major birch pollen allergen, as proved by reactivity with purified natural as well as with recombinant allergen. The T cell clones were used to investigate common T cell epitopes of the Bet v I molecule with Cor a I, the major allergen of hazel pollen and Aln g I, the major allergen of alder pollen. All eight T cell clones reacted with all three proteins with different intensity. Moreover, three T cell clones, which were known to react with immunodominant T cell epitopes on the Bet v I molecule, were tested for reactivity with dodecapeptides synthesized according to the corresponding homologous regions of the Cor a I and Aln g I sequence. All the peptides induced strong T cell proliferation, indicating the existence of multiple cross-reacting epitopes. These findings will have an impact on the production of vaccines for immunotherapy of tree pollen allergies.

Allergens↗