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Biomedical subjects

H Hofmann

Publications and source records attributed to H Hofmann.

At least 19 recordsLinked to original sources

Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging of atherosclerotic plaques.

INTRODUCTION: Superparamagnetic iron oxide nanoparticles (SPIONs) have been successfully used for magnetic resonance imaging (MRI) of atherosclerotic plaques. Endocytosis into monocytes/macrophages has been proposed as the mechanism for SPION uptake, but a specific receptor has not been identified yet. A potential candidate is the versatile integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is involved in leukocyte adhesion, complement activation and phagocytosis. METHODS AND RESULTS: Intracellular SPION-accumulation was confirmed in cultured human monocytes using immunohistochemistry and iron staining. Recombinant cells expressing Mac-1 in different activation states as well as human monocytes with or without PMA stimulation were incubated either with an unspecific IgG or a CD11b-blocking antibody. Thereafter, cells were incubated with FITC-labeled amino-covered SPIONs or ferumoxtran-10 SPIONs and signal intensity was quantified by flow cytometry. Depending on the activation status of Mac-1, a significant increase in SPION binding/uptake was observed, independent on surface coating. Furthermore, SPION binding/uptake was significantly reduced after CD11b blockade. Results were confirmed in recombinant cells incubated with amino-PVA SPIONs and ferumoxtran-10, using T2(*)-weighted 3T MRI. CONCLUSION: The integrin Mac-1 is directly involved in SPION binding/uptake. Thus, monocytes abundantly expressing Mac-1 and especially activated monocytes expressing activated Mac-1 may be useful vehicles for high resolution MRI labeling of atherosclerotic plaques.

Animals↗

[Early diagnosis of Lyme borreliosis].

The local inflammatory reaction following a tick bite varies considerably, so that in particular the frequently atypical variations result in a wrong diagnosis and thus to inappropriate treatment. If a tick bite is followed within three weeks by flue-like or neurological symptoms, or joint swelling in the vicinity of the bite, a serological investigation work-up should be carried out. In the early stage, however, Borrelia-specific antibodies can be detected in only 30-80% of the patients. However, during the further course of the illness, the specific IgM and IgG antibody titers almost always increase.

Anti-Bacterial Agents↗

[Virtual microscopy and digital pathology].

Virtual microscopy has advanced considerably and is bound to be integrated into routine diagnostics in the very near future. Its integration into existing information systems builds up digital pathology. In this review, we present details, advantages and limitations of this novel technology and describe solutions regarding its adaptation to routine workflow. The chief aim is to define an uniform data format for virtual specimens to guarantee an interoperability between different systems. In the long term, digital archives and networks will be established that will allow for a worldwide access to virtual specimens.

Humans↗

Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus.

BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy. OBJECTIVES: To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.

Adolescent↗

[Current hygiene status in endoscopic practice. Results from monitoring the reprocessing of flexible endoscopes in hospitals and private practices in Frankfurt on the Main, Germany, 2003/4].

Flexible endoscopy is essential for the practice of modern medicine. However, with inadequate reprocessing of endoscopes and additional instruments, infections can be transmitted. Therefore, guidelines for reprocessing flexible endoscopes have been published in many countries. The goal of the present survey was to examine the current compliance with German Guidelines in a German urban region, covering all hospitals (15 hospitals) and private practices (23 practices) of this area, without any exception. All endoscopic units in Frankfort on the Main were visited by members of the Public Health Service, using a checklist based on the recommendations of the German Guidelines. In 2004, a reevaluation of 14 hospitals and 20 private practices took place, either by analysing the written reports of the institutions or by revisiting the institutions. In 2003, compliance with the guidelines in hospitals was satisfactory. In practices, however, many problems were identified in 2003. Between 2003 and 2004, great improvements could be seen (data of 2003 in parentheses). At the end of 2004, in 90% of the practices adequate storage of the endoscope without risk of recontamination (2003:52%), correct reprocessing the bottle and the tube for air/water channel flushing including filling with sterilized water was observed (2003:74% and 52%). In 100% of the practices, ultrasonic cleaning (2003:26%) and sterilizing of endoscopic accessories was guaranteed (2003:57%) and routine tests of endoscopes after reprocessing (2003:56%) were performed. In conclusion the relevance and the effect of the advising and control of public health have been so efficient that between 2003 and 2004 most faults have been corrected. Therefore control visits of the Public Health Services should not only cover hygiene in reprocessing the endoscopes but also hygiene in reprocessing endoscopic accessories as well.

Endoscopy↗

[Lyme borreliosis. Cutaneous manifestation].

Lyme borreliosis is a tick transmitted infectious disease caused by different genospecies of Borrelia burgdorferi sensu lato. In USA only one species B. burgdorferi sensu stricto is prevalent, whereas in Europe at least 5 different pathogenic species could be identified. The most prevalent species are B. afzelii and B. garinii. Infection is not always causing disease. In early infection, a localized skin inflammation, called erythema migrans, occurs around the tick bite, hematogenous dissemination of Borrelia causes flu like symptoms up to meningitis and multiple erythemata migrantia on the skin. In late stage multiple organ systems can be affected, in Europe especially the skin with various forms of acrodermatitis chronica atrophicans, the central and peripheral nervous system, joints and heartmuscle. Lyme borreliosis can be diagnosed by the typical history, the clinical symptoms and the elevated Borrelia specific IgM- and IgG-antibodies in serum and CSF according to the MIQ guidelines, in special cases B. burgdorferi can be cultivated or DNA detected by PCR. Therapy of choice for early infection is oral antibiotics like doxycycline, amoxicillin and cefuroxime for at least 10 days up to 21 days. Late stage infections should be treated for 3-4 weeks. Patients with neurological symptoms should be treated intravenously with ceftriaxone or penicillin G.

Borrelia burgdorferi↗

Development of functionalized superparamagnetic iron oxide nanoparticles for interaction with human cancer cells.

Our goal is to develop, characterize and optimize functionalized super paramagnetic iron oxide nanoparticles (SPION) demonstrating the capacity to be internalized by human cancer cells. SPION (mean diameter 9nm) were coated with various ratios to iron oxide of either polyvinyl alcohol (PVA), carboxylate-functionalized PVA, thiol-functionalized PVA and amino-functionalized PVA (amino-PVA). The interaction with cells and cytotoxicity of the SPION preparations were determined using human melanoma cells. From the four functionalized SPION preparations, only the amino-PVA SPION demonstrated the capacity to interact with, and were not cytotoxic to, human melanoma cells. This interaction with melanoma cells was dependent on the amino-PVA to iron oxide ratio, was an active and saturable mechanism displayed by all cells in a culture. These functionalized SPION were characterized by transmission electron microscopy and electrophoretic mobility. The physical comportment of SPION changed at specific PVAs to iron oxide ratios, and this ratio corresponded to the ratio of optimal interaction with cells. In conclusion, the successful development of functionalized SPION displaying potential cellular uptake by human cancer cells depends both on the presence of amino groups on the coating shell of the nanoparticles and of its ratio to the amount of iron oxide.

Cell Line, Tumor↗

Invasive chromoblastomycosis and sinusitis due to Phialophora verrucosa in a child from northern Africa.

We report on a severe, verrucous facial mycosis and sinusitis in a 12-year-old Libyan girl. Her disease started with verrucous, hyperkeratotic plaques and subcutaneous violet nodules of unknown origin on her face and upper extremities. Despite topical antimycotic therapy she needed in-hospital treatment because of severely progressive tumorous cutaneous and nasal lesions. Microscopic examination of scale samples taken from the upper extremities and the face revealed brown, thick-walled fungal elements. Under the assumption of a chromoblastomycosis, an oral treatment with itraconazole and fluorocytosin was initiated, with significant improvement of the lesions. The aetiological agent was identified as Phialophora verrucosa.

Antifungal Agents↗

Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study.

BACKGROUND: Chronic neuropathic pain occurs in 10-15% of patients with neuroborreliosis and is difficult to treat. OBJECTIVE: We evaluated the effect of gabapentin monotherapy on residual pain in patients with neuroborreliosis after intravenous ceftriaxone treatment. METHODS: Ten patients with neuroborreliosis and a long-lasting history of neurologic symptoms were treated with gabapentin, starting with 300 mg/day. Doses were raised over a period of 4-12 weeks to the individually effective and tolerated maximum dose (500-1,200 mg). Treatment was maintained until pain disappeared and then gradually reduced in dose over weeks. If symptoms recurred, the doses were raised again. Therapy was maintained over an average of 1-2 years. RESULTS: Pain quality and pain quantity were evaluated using the McGill pain questionnaire and a visual analogue scale. There was an improvement of 'crawling' and 'burning' pain sensations, neck and radiating lumbar pain in 9/10 (90%) patients as well as a positive effect on mood, general feeling of health and quality of sleep in 5/10 (50%) patients. The average dose leading to a clear-cut pain reduction was 700 mg. CONCLUSIONS: In an open pilot study (10 patients), gabapentin monotherapy which has to our knowledge not been published as treatment of chronic neuropathic pain in patients with late Lyme borreliosis is efficacious in treating pain associated with neuroborreliosis and can thus improve quality of life in these patients.

Administration, Oral↗

Particle size investigations of a multistep synthesis of PVA coated superparamagnetic nanoparticles.

Nanoscaled particles showing superparamagnetic behavior have been intensively studied in the past years for various applications. Nevertheless, the lack of well-defined particles remains an important problem. One of the major challenges is still the large-scale synthesis of particles with a narrow size distribution. The aim of this work is to synthesize and characterize ferrofluids throughout a multistep synthesis. The iron oxide nanoparticles are first obtained by classical coprecipitation in water, followed by a thermochemical treatment and centrifugation to obtain well-dispersed primary nanoparticles. Finally polyvinyl alcohol is grafted onto the particles to ensure colloidal stability of the ferrofluid at neutral pH. The different synthesis steps and intermediate and side products are described. A model is proposed for the stabilization mechanism.

Journal Article↗

[Hygiene in endoscopy in the clinic and practice, 2003: Results of infection hygiene survey on endoscopy services in Frankfurt am Main by the public health service].

UNLABELLED: Guidelines for reprocessing flexible endoscopes have been published in many countries. Compliance to the German guidelines, published in 2002 by the Commission on Hospital Hygiene and Infection Prevention on the Robert Koch Institute is mandatory in all endoscopic units, in hospitals as well as in private practices. Here, a survey of current reprocessing practices in an urban region in Germany is published, covering all hospitals and private practices in this region. MATERIAL AND METHODS: In summer 2003, all endoscopic units in Frankfurt/Main, Germany--15 hospitals and 23 private practices -- were visited by members of the public health service, using a checklist based on the recommendations of the German guideline. RESULTS: In these institutions, more than 70 000 endoscopic examinations per year are performed. 87 % (13 /15) of the hospitals and 43 % (10/23) of the practices, reported to conduct more than 1000 procedures per year. Great differences were found in hygienic quality comparing endoscopic units in hospitals and in private practices. In hospitals compliance with the guidelines was satisfactory. Main problems in the practices were: missing facilities for ultrasonic cleaning (74%) and sterilizing (43%), faults in reprocessing the bottle and tube for air/water-channel flushing (26%) which was filled in with water not sterilised (48%), storage of the endoscope with risk of recontamination (48%), missing routine-tests of the endoscopes after reprocessing (44%). Generally, hygienic conditions and procedures were worse in smaller units than in bigger ones. DISCUSSION: The data from Frankfurt hospitals are satisfactory. In private practices, however, especially in smaller ones, improvements are mandatory. Improvements should cover the quality of structure and process, i.e. specific education of the nurses, availability of ultrasonic cleaners and sterilizators and -- preferably -- automatic dishwashers, as well as implementation of a written protocol for hygiene in endoscopy, based on the German Guidelines.

Endoscopes↗

The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass.

OBJECTIVE: Neuropsychologic disorders are common after coronary artery bypass operations. Air microbubbles are identified as a contributing factor. A dynamic bubble trap might reduce the number of gaseous microemboli. METHODS: A total of 50 patients undergoing coronary artery bypass operation were recruited for this study. In 26 patients a dynamic bubble trap was placed between the arterial filter and the aortic cannula (group 1), and in 24 patients a placebo dynamic bubble trap was used (group 2). The number of high-intensity transient signals within the proximal middle cerebral artery was continuously measured on both sides during bypass, which was separated into 4 periods: phase 1, start of bypass until aortic clamping; phase 2, aortic clamping until rewarming; phase 3, rewarming until clamp removal; and phase 4, clamp removal until end of bypass. S100 beta values were measured before, immediately after, and 6 and 48 hours after the operation and before hospital discharge. RESULTS: The bubble elimination rate during bypass was 77% in group 1 and 28% in group 2 (P <.0001). The number of high-intensity signals was lower in group 1 during phase 1 (5.8 +/- 7.3 vs 16 +/- 15.4, P <.05 vs group 2) and phase 2 (6.9 +/- 7.3 vs 24.2 +/- 27.3, P <.05 vs group 2) but not during phases 3 and 4. Serum S100 beta values were equally increased in both groups immediately after the operation. Group 2 patients had higher S100 beta values 6 hours after the operation and significantly higher S100 beta values 48 hours after the operation (0.06 +/- 0.14 vs 0.18 +/- 0.24, P =.0133 vs group 2). Age and S100 beta values were correlated in group 2 but not in group 1. CONCLUSION: Gaseous microemboli can be removed with a dynamic bubble trap. Subclinical cerebral injury detectable by increases of S100 beta disappears earlier after surgical intervention.

Aged↗

[Early diagnosis of Lyme borreliosis. Do not look only for erythema migrans].

Although the typical erythema migrans is a relatively easy-to-recognize manifestation of Lyme borreliosis, it is by no means the sole cutaneous manifestation of infection with borreliae. In particular the early stages of the disease, with their paucity of symptoms or wide variability of the clinical symptomatology, often present a diagnostic challenge. This means that in the event of unclear unspecific cutaneous lesions indicating, for example, erysipelas or urticaria, Lyme borreliosis should also receive differential diagnostic consideration. Culture of the organism, DNA-based confirmation of B. burgdorferi or, where indicated, a serological investigation can confirm the diagnosis at an early stage. The treatment of choice compromises an antibiotic administered for an adequate duration and at an adequate dose, e.g. doxycycline 2 x 100 mg over three weeks). If treatment is initiated in a local or disseminated early stage, healing rates of more than 85% can be achieved.

Adult↗

Self-consistent quantal treatment of decay rates within the perturbed static path approximation.

The framework of the perturbed static path approximation is used to calculate the partition function of a finite Fermi system from a Hamiltonian with a separable two body interaction. Therein, the collective degree of freedom is introduced in self-consistent fashion through a Hubbard-Stratonovich transformation. In this way, all transport coefficients that dominate the decay of a metastable system are defined and calculated microscopically. Otherwise the same formalism is applied as in the Caldeira-Leggett model to deduce the decay rate from the free energy above the so called crossover temperature T(0).

Journal Article↗

Analysis of interleukin-4 receptor alpha chain variants in multiple sclerosis.

A recent candidate gene study employing microsatellite markers suggested a possible linkage of multiple sclerosis (MS) with the interleukin-4 receptor (IL4R) gene. Consequently, we investigated the association of different IL4R variants with MS in 341 German MS patients and 305 healthy controls. Analysis of the first 100 MS patients for six IL4R variants showed an increased frequency of the R551 variant in MS patients versus healthy controls and carriage of the same IL4R variant was weakly associated with myelin oligodendrocyte glycoprotein (MOG) autoantibody production. However, further analysis of all 341 MS patients did not confirm the finding that this IL4R variant represents a general genetic risk factor for MS but revealed an increased frequency of the R551 variant in MS patients with primary progressive MS (PPMS, n=48) as compared to patients with relapsing remitting MS or secondary progressive MS (RR/SPMS n=284; P=0.005 for genotype differences) and to 305 healthy controls (P=0.001 for genotype differences). This association was statistically independent of the presence of the well-known MS susceptibility allele HLA-DRB1*15. After correction for multiple comparisons only the genotype differences between PPMS patients and healthy controls remained statistically significant. These results indicate, that the IL4R variant R551 may influence the genetic predisposition for PPMS but does not represent a general genetic risk factor for MS.

Adult↗