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Biomedical subjects

A Hildebrand

Publications and source records attributed to A Hildebrand.

At least 19 recordsLinked to original sources

[Familial syringoma: a rare clinical variant].

Syringomas usually occur either sporadically in a periorbital localized or truncal eruptive form. We report on two families with very uncommon hereditary syringomas. Multiple syringomas developed in the periorbital area of affected patients in the first family while the face, neck, trunk, and extremities were involved in the second family. The lesions first appeared during puberty and their number and distribution varied among the family members. Autosomal dominant inheritance equally affecting both sexes appears most likely. The incidence of familial syringomas may be widely underestimated. For treatment, carbon dioxide laser yielded good results while an excellent cosmetic outcome was achieved on the face with a special surgical technique using a springaction microscissors.

Adult↗

Bioadhesion of supramolecular structures at supported planar bilayers as studied by the quartz crystal microbalance.

A quartz crystal microbalance (QCM) was used to study the adhesion behavior of supramolecular aggregates at supported planar bilayers (SPBs). The QCM technique is a suitable method to detect the adsorption of biomolecules at the quartz surface owing to its sensitivity for changes in mass and viscoelastic properties. To simulate biomembranes, the quartz plates were coated with highly ordered lipid films. Therefore, a combination of self-assembled monolayers and Langmuir-Blodgett films was used. Firstly, the adsorption of liposomes coupled with the lectin concanavalin A was investigated at glycolipid-containing model membranes. Using different carbohydrates, it was possible to determine specific and nonspecific parts of the interactions. The adhesion occurred owing to specific lectin-carbohydrate interactions (about 20%) and to nonspecific interactions (about 80%). The composition of the liposomes was changed to simulate the structure of a native biomembrane consisting of the glycocalix, the lipid-protein bilayer, and the cytoskeleton. An artificial glycocalix was created by incorporating poly(ethylene glycol) into the liposomes. Liposomes which were intravesicular polymerized with polyacrylamide or polyacrylcholate simulated the cytoskeleton. It was determined that the modified liposomes had significant lower interactions with SPBs. The adsorption was reduced by approximately 80% compared to unmodified liposomes. Secondly, a model was developed for the detection of interactions between simple or mixed bile salt micelles and model membranes. It was found that simple bile salts did not adsorb at model membranes. Binary systems consisting of bile salt and phospholipid induced only small interactions. On the other hand, ternary systems consisting of bile salt, phospholipid, and fatty acid showed strong interactions. A dependence on the chain length of the fatty acid was observed. Thirdly, the interaction between ganglioside-containing model membranes and cholera toxin (beta-subunit) was investigated. Different ganglioside fractions showed varying adsorption in the following sequence: GM1 > GD1a > GD1b > GT1b.

1,2-Dipalmitoylphosphatidylcholine↗

Immunophenotypic analysis of simultaneous specimens from different sites from the same patient with malignant lymphoma.

Immunophenotypic analysis of simultaneous specimens from different sites from the same patient with malignant lymphoma The assumption that immunophenotypic characteristics of different specimens obtained simultaneously from the same patient remain unchanged has rarely been evaluated. Using flow cytometry, we reviewed our experience of 29 patients with non Hodgkin's lymphoma (NHL). From these patients, 60 simultaneous specimens taken from the peripheral blood, bone marrow, effusions, fine needle aspirates from lymph nodes or cerebrospinal fluid were studied. In 26 out of 29 patients, the immunophenotype in the different specimens was identical. In one patient with unclassifiable low-grade B-NHL, immunophenotyping showed additionally a CD38 expression in the effusion which was not seen in the bone marrow. In one patient with mantle cell lymphoma, expression of CD10 in the lymph node was noted which was lacking in the peripheral blood. In the remaining patient with unclassifiable low-grade B-NHL, CD23 expression was noted in the lymph node but not in the peripheral blood. This retrospective study suggests that discordant antigen expression in samples from different body sites within the same patient is a rare event.

Antigens, CD↗

[3D models for diagnosis and treatment planning in cardiology].

Due to the development new of imaging devices which produce a large number of tomographic slices, advanced techniques for the evaluation of the large amount of data are required. Computer supported extraction of dynamic 3D-models of the patients anatomy from temporal series thus is highly desirable. Since the diagnostician should be able to quickly make sensible decisions based on the models, high accuracy is required within a minimum of time. We present modeling and visualization techniques that are realized within the Cardiac Station. Results for the application of these techniques to cardiac image data demonstrate their usability. Besides giving information about the patients morphology functional parameters can be derived from the data and visualized together with the model. In order to verify the model with the original image data and for the planning of real intervention interaction techniques are presented.

Anatomy, Cross-Sectional↗

Healing characteristics of small-calibre vascular prostheses coated with plasmin-treated fibrin--an experimental study.

BACKGROUND: The autogenous vein represents the graft material of choice in crural and pedal bypass surgery. Because of the numerous problems concerning the graft harvesting and the quality of autogenous vein material an equally good allogenous graft is urgently needed. Up to the present times no such graft material has been able to achieve the success of vein grafts. METHODS: We investigated the knitted polyester prosthesis Terumo PF-V (Terumo Comp., Japan), diameter 5 mm with outer reinforce, which is characterized by a new coating of plasmin-treated fibrin. Grafts were implanted as bypass into the ligated carotid (n = 10) and femoral arteries (n = 10) of 10 dogs (beagles). As a control 5 mm-ePTFE-prostheses (Impra Carboflo) were implanted simultaneously on the contralateral side. RESULTS: After 6 months, seven of 20 PF-V-grafts and 8 of 20 PTFE-grafts were patent. All prostheses presented with good macroscopic healing characteristics. In the patent grafts, angiography showed no substantial stenoses. The histological examination of the material was performed using light microscopy, transmission polarising microscopy, scanning electron microscopy, and transmission electron microscopy. Both types of prostheses showed the typical pattern of graft healing by migration of mesenchymal cells through the prosthesis, formation of capillaries, and growing of a neointima with endothelium-like cells. All failed bypass grafts presented with an occluding proliferation from the arterial wall into the anastomotic region. CONCLUSIONS: Using clinically or histologically evaluation, neither graft demonstrated superiority over the other. The results indicate that the coating plays only a minor role for graft healing if any. For proper graft function, the arterial wall proliferation at the anastomotic region, which is not dependent on the type of prosthesis, appears to be most important. The overall results concerning both types of prostheses were disappointing.

Animals↗

Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies.

OBJECTIVE: To evaluate treatment and outcome of 17 pregnancies in nine patients with essential thrombocythaemia (ET) seen at our institution from 1988 to 1998. METHODS: Treatment and outcome of 17 pregnancies in nine ET patients were retrospectively analyzed. RESULTS: Seventeen pregnancies in nine patients with ET resulted in 11 (65%) live births and ended in six (35%) spontaneous abortions. Abortion could not be predicted from ET-associated complications before (p= 0.23) or during (p = 0.39) pregnancy. Maternal complications occurred during six pregnancies (35%): Three major bleedings in two patients with an acquired von Willebrand disease and two minor bleedings in patients treated with low-dose acetylsalicylic acid (ASA) were observed during pregnancy or at term; one patient suffered from transient visual loss while pausing low-dose ASA. Platelet counts prior to pregnancy were significantly higher as compared to the platelet nadir observed during pregnancy (p = 0.0017). Postpartum clinical course was uneventful in all patients. No specific treatment was given during 11 pregnancies. Six women received low-dose ASA during pregnancy followed by low-molecular-weight heparin until the end of the sixth week postpartum in five cases. This treatment was correlated with a favourable outcome (live birth versus abortion) when compared to no treatment (p=0.04). CONCLUSION: Pregnancy in ET can be complicated by first trimester abortion and/or maternal haemorrhage. Our limited observation suggest a positive impact of low-dose ASA during pregnancy followed by low-molecular-weight heparin postpartum on pregnancy outcome in ET; nevertheless, confirmation by prospective documentation is mandatory.

Abortion, Spontaneous↗

Lactate concentration in plasma and red blood cells during incremental exercise.

The purpose of this study was to investigate the distribution of lactate in plasma and red blood cells (RBC) in capillary blood during and after incremental exercise. We measured capillary plasma lactate and whole blood lactate of 10 subjects during incremental treadmill running and the first 20 min of recovery. To minimize lactate exchange from plasma to RBC between sampling and analysis, a recently developed rapid plasma separation method was used. RBC lactate was calculated. The RBC/plasma lactate concentration ratio decreased from 1.0 (0.85-1.28) before to 0.37 (0.25-0.45) after exhaustive exercise (plasma lactate 15.9 (12.2-19.5)mmol x I(-1), RBC lactate 4.8 (4.0-7.0) mmol x 1(-1)), thus showing that capillary plasma lactate increased much more rapidly than intracellular lactate during incremental exercise. In the first 5 minutes of recovery intracellular lactate still rose while plasma lactate already declined. Then both decreased while the concentration ratio as well as the absolute concentration gradient remained nearly constant (ratio 20 min after exercise termination: 0.43 (0.19-0.54).

Adolescent↗

Paroxysmal nocturnal haemoglobinuria: a replacement of haematopoietic tissue?

Acquired somatic mutations of the PIG-A gene lead to deficient expression of glycosyl-phosphatidyl-inositol-anchored proteins (GPI-AP) by haematopoietic cells and play a causative role in the pathogenesis of paroxysmal nocturnal haemoglobinuria (PNH). However, PIG-A mutations do not explain how the defective PNH clone can expand. It was hypothesized that a selection process conferring a relative advantage to the GPI-AP-deficient population is required. Since GPI-AP-deficient cells are also detectable in a substantial proportion of patients with otherwise typical aplastic anaemia (AA), the mechanisms inducing bone marrow failure might selectively spare the GPI-deficient cells. In order to examine the growth characteristics of GPI-AP-deficient cells in more detail, we performed repeated analyses of GPI-AP expression on peripheral blood cells in 41 patients with AA. We observed four patterns of the course of GPI-AP-deficient populations: (1) 13 patients showed normal expression of GPI-AP in the first analysis and in at least two follow-up studies at a median time of 709 days after the first analysis. (2) Secondary evolution of a GPI-AP-deficient population was a rare event. Only 4 patients with initially normal GPI-AP expression developed a GPI-AP-deficient population during follow up after immunosuppressive treatment. (3) Persistence of GPI-AP-deficient cells was observed in 16 patients during a median follow-up time of 774 days. However, in some patients, the size of the GPI-AP-deficient population increased substantially. (4) Disappearance of a GPI-AP-deficient population was observed in 8 patients. The time course of GPI-AP expression in relation to the treatment suggests that therapeutic interventions might modulate the ratio of normal versus GPI-AP-deficient haematopoiesis. Overall, these data argue against an 'absolute growth advantage' of GPI-AP-deficient cells. Our data are consistent with the hypothesis that haematopoietic failure caused by damage to normal haematopoiesis allows the outgrowth of a GPI-AP-deficient population. Thus, in at least some patients GPI-AP-deficient cells might pre-exist at a very low percentage and replace haematopoiesis after an insult to the normal cells.

Anemia, Aplastic↗

Diagnosis of granulocytic sarcoma by fine-needle aspiration cytology.

Granulocytic sarcoma (GS) occurs in patients with chronic myeloproliferative disorders as well as in patients with acute myeloid leukemia (AML). These tumorous masses can occur anywhere in the body and have to be differentiated from lymphoma, carcinoma or infectious processes. We report the results of fine-needle aspiration cytology (FNAC) in 26 patients with GS. Seventeen patients suffered from AML and 9 from chronic myeloid leukemia (CML) blast crisis. In 5 patients with AML, GS was the initial presentation of hematological malignancy, in the remaining 21 patients, FNAC confirmed relapse of AML or extramedullary blast crisis of CML. In 8 patients, GS was located in the skin, in 17 in the lymph node and in another patient in the spinal canal. This study demonstrates the clinical utility and diagnostic accuracy of FNAC in the evaluation of GS from multiple sites.

Acute Disease↗

[Congenital poikiloderma with verruciform hyperkeratoses (Dowling type)].

A male patient with congenital poikiloderma (type Dowling) developed Bowen's disease and initial squamous cell carcinoma. As the patient suffered from hypertriglyceridaemia (Frederickson type IV) and a long term tumor prophylaxis with retinoids was not appropriate, we attempted to treat the hyperkeratotic plaques with dermabrasion. After a period of six month we found complete healing of several plaques and only slight keratoses left in a few others. Long term follow up results are not yet available. Through this case report, the heterogenous clinical picture of congenital poikiloderma with warty hyperkeratoses and its high risk of malignancies is discussed.

Bowen's Disease↗

[Prurigo pigmentosa].

We report the first case of prurigo pigmentosa in the German literature. For over a year, a 16-year old white girl developed an immensely pruritic symmetrical reticular, papulovesicular eruption on the trunk, axillae and pubic region. Histologically a superficial perivascular spongiotic and lichenoid inflammatory pattern with prominent pigmentary incontinence in older lesions was observed. Topical corticosteroids and systemic antihistamines had no effect. Systemic corticosteroids and diaminophenylsulphone (DADPS) produced improvement but could not prevent recurrences. Healing occurred only after 4 weeks of systemic-minocycline.

Adolescent↗

Recent developments in the treatment of atopic eczema.

Atopic eczema remains a therapeutic challenge. However, new developments in the understanding of the pathogenesis of this complex disease have prompted new therapeutic strategies. This review focuses on recently described treatment modalities for atopic eczema that are currently available or under investigation. The effectiveness of phototherapy, cytokines, and immunosuppressive drugs is evaluated. In addition, some new and promising but still experimental approaches are discussed.

Cytokines↗

Virtual reality in the operating room of the future.

In cooperation with the Max-Delbrück-Centrum/Robert-Rössle-Klinik (MDC/RRK) in Berlin, the Fraunhofer Institute for Computer Graphics is currently designing and developing a scenario for the operating room of the future. The goal of this project is to integrate new analysis, visualization and interaction tools in order to optimize and refine tumor diagnostics and therapy in combination with laser technology and remote stereoscopic video transfer. Hence, a human 3-D reference model is reconstructed using CT, MR, and anatomical cryosection images from the National Library of Medicine's Visible Human Project. Applying segmentation algorithms and surface-polygonization methods a 3-D representation is obtained. In addition, a "fly-through" the virtual patient is realized using 3-D input devices (data glove, tracking system, 6-DOF mouse). In this way, the surgeon can experience really new perspectives of the human anatomy. Moreover, using a virtual cutting plane any cut of the CT volume can be interactively placed and visualized in realtime. In conclusion, this project delivers visions for the application of effective visualization and VR systems. Commonly known as Virtual Prototyping and applied by the automotive industry long ago, this project shows, that the use of VR techniques can also prototype an operating room. After evaluating design and functionality of the virtual operating room, MDC plans to build real ORs in the near future. The use of VR techniques provides a more natural interface for the surgeon in the OR (e.g., controlling interactions by voice input). Besides preoperative planning future work will focus on supporting the surgeon in performing surgical interventions. An optimal synthesis of real and synthetic data, and the inclusion of visual, aural, and tactile senses in virtual environments can meet these requirements. This Augmented Reality could represent the environment for the surgeons of tomorrow.

Computer Simulation↗

Successful treatment of generalized lichen planus with recombinant interferon alfa-2b.

Three patients with generalized lichen planus were treated with interferon alfa-2b. The therapy was tolerated well by all patients with only minor side effects. A response was observed within 2 to 3 weeks. Itching and erythema decreased first, followed by gradual flattening and disappearance of papules and plaques after 8 to 10 weeks of treatment. After 12 weeks, therapy was discontinued after stepwise dosage reduction. In two patients, minor lesions recurred during dosage reduction. Both flares were controlled by readministration of interferon.

Adult↗

Successful treatment of epidermolysis bullosa acquisita using intravenous immunoglobulins.

We report a 55-year-old man with severe inflammatory epidermolysis bullosa acquisita. The skin lesions did not respond to various immunosuppressive treatments. The combined administration of prednisone, azathioprine, dapsone and colchicine resulted only in a transient and incomplete resolution of the lesions. The bullae and increased skin fragility were successfully controlled by the addition of high-dose intravenous immunoglobulin therapy.

Azathioprine↗

Eosinophilic pustular folliculitis: successful treatment with interferon-alpha.

Eosinophilic pustular folliculitis (Ofuji's disease) is a rare skin disease of unknown etiology characterized by infiltrated circinate plaques with sterile follicular pustules in primarily seborrheic areas. Several therapeutic regimens have been reported to control the disease with inconsistent results. We here report on a patient with Ofuji's disease, who was successfully treated with interferon-alpha 2b.

Adolescent↗

Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.

We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with Kd values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin in endothelial cells was reduced, but the binding to the type-II receptors was unaffected. TGF-beta 2 and 3 also bound to all three fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.

Biglycan↗

Histidine residues near the N terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation.

Chemical modification of histidine residues in staphylococcal alpha-toxin leads to loss of functional activity. Site-directed mutants of the toxin in which each of the four histidine residues was replaced by several amino acids were therefore produced. The mutant proteins were purified and characterized. Exchange of H-259 or H-144 was sometimes tolerated without reduction in hemolytic activity. These histidine residues are thus not essential for toxin function. Exchange of H-35 and H-48, however, had marked effects. H-35 mutant toxins bound with high affinity to rabbit erythrocytes but displayed faulty oligomerization and were unable to form pores. H-48 mutant toxins also had severely impaired hemolytic activity due probably to faulty hexamerization. We interpret these results to indicate that the N-terminal domain of alpha-toxin in the region of H-35 and H-48 is involved in protomer-protomer interactions that underlie the hexamerization and pore-forming process.

Animals↗