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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 19 recordsLinked to original sources

[Retained foreign bodies from the surgical point of view].

The number of foreign bodies remaining in the patient after a surgical procedure is presumably higher than mentioned in the literature. According to US insurance statistics, the incidence amounts to 1 in 1,500 surgical procedures. As a basic principle--also from the legal aspect--it is necessary to determine whether a foreign body was left in situ accidentally (i.e. due to a material fault) or if it was simply forgotten. In 70% of cases, fabric items (e.g. swabs etc.) are left behind, while around 30% are metal objects. A particularly high risk is seen in emergency settings, in unexpected changes in the surgical procedure, or for patients with a high body mass index. The outcome for the patient differs depending on the nature of the object left behind and the individual patient's situation. Usually, metal items cause more acute clinical symptoms at an earlier time after the operation. Fabric items tend to induce, in the absence of primary contamination, a chronic progression of symptoms over several years. Reoperation has a high mortality (between 11% and 35%). Precautions in terms of risk management have to be established and need to be strictly respected, especially in high risk settings. Visually or acoustically controlled monitoring before wound-closure are recommended to eliminate "human error" as thoroughly as possible.

Cross-Sectional Studies↗

Mediator release assays based on human or murine immunoglobulin E in allergen standardization.

BACKGROUND: The biological potency of allergens can be measured by provoking mediator release from effector cells. As established immunochemical methods in allergen standardization only determine inhibition potency or major allergen content, routine tests for biological potency may enhance standardization and batch control of allergen products. OBJECTIVE: The general performance and application potential of biological in vitro assays in batch control and standardization of allergens and as a tool for verifying activity and stability of allergen standards were analysed. METHODS: Allergen extracts of five clinically relevant allergens from three to five different manufacturers were investigated. A CAP-IgE-inhibition assay was compared with mediator release assay (MRA)s based on murine or human basophils. Rat basophilic leukaemia (RBL) cells were passively sensitized with pooled murine allergen-specific IgE-containing sera. Humanized RBL cells and human-stripped basophils were sensitized with pooled patient's sera, which were also used for the CAP-IgE-inhibition assay. Allergen specificity of the sera was determined by immunoblotting. RESULTS: A good batch-to-batch consistency was found with each assay among all manufacturers and allergens tested. Between different manufacturers, the products showed differences in activity and the various assays indicated an almost identical ranking. However, the biological assays revealed qualitative differences of biological activity or composition of allergen preparations undetectable by IgE-inhibition assay. CONCLUSIONS: MRAs provide refined information on allergen activity, either confirming the results of IgE-inhibition assay, or indicating differences requiring further investigation, and represent a highly sensitive novel tool in allergen standardization. By using permanently cultivated cell lines, repeated venepuncture to obtain human basophils is avoided. As in the RBL assay, the coefficient of variation for the release values were below 15% and for the ED50 below 25%, the assay is suitable to determine differences that are relevant for batch control purposes.

Allergens↗

Bulk chemical shifts in hydrogen-bonded systems from first-principles calculations and solid-state-NMR.

We present an analysis of bulk (1)H NMR chemical shifts for a series of biochemically relevant molecular crystals in analogy to the well-known solvent NMR chemical shifts. The term bulk shifts denotes the change in NMR frequency of a gas-phase molecule when it undergoes crystallization. We compute NMR parameters from first-principles electronic structure calculations under full periodic boundary conditions and for isolated molecules and compare them to the corresponding experimental fast magic-angle spinning solid-state NMR spectra. The agreement between computed and experimental lines is generally very good. The main phenomena responsible for bulk shifts are packing effects (hydrogen bonding and pi-stacking) in the condensed phase. By using these NMR bulk shifts in well-ordered crystalline model systems composed of biologically relevant molecules, we can understand the individual spectroscopic signatures of packing effects. These local structural driving forces, hydrogen bonding, pi-stacking, and related phenomena, stand as a model for the forces that govern the assembly of much more complex supramolecular aggregates. We show to which accuracy condensed-phase ab initio calculations can predict structure and structure-property relationships for noncovalent interactions in complex supramolecular systems.

Journal Article↗

Transcriptional regulation via the NF-kappaB signaling module.

Stimulus-induced nuclear factor-kappaB (NF-kappaB) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of kappaB (IkappaB) proteins controls NF-kappaB DNA-binding activity and nuclear localization. IkappaB protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-kappaB activity. This network of interactions has been termed the NF-kappaB signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-kappaB dimer formation and the signal-processing characteristics of the signaling module. We identify NF-kappaB-kappaB site interaction specificities and dynamic control of NF-kappaB activity as mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-kappaB-mediated gene activation.

Animals↗

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Journal Article↗

Imprinting vortices into antiferromagnets.

The effect of imprinting symmetric and displaced vortex structures into an antiferromagnetic material is investigated in micron-sized disks consisting of exchange coupled ferromagnetic-antiferromagnetic bilayers. The imprint of displaced vortices manifests itself by the occurrence of a new type of asymmetric hysteresis loops characterized by curved, reversible, central sections with nonzero remanent magnetization. Such an imprint is achieved by cooling the disks through the blocking temperature of the system in small fields. Micromagnetic simulations reveal that asymmetric vortexlike loops naturally result from the competition between the different energies involved in the system.

Journal Article↗

The Calibration Kit Spectral Fluorescence Standards--a simple and certified tool for the standardization of the spectral characteristics of fluorescence instruments.

With the Calibration Kit Spectral Fluorescence Standards BAM-F001-BAM-F005, we developed a simple tool for the characterization of the relative spectral responsivity and the long-term stability of the emission channel of fluorescence instruments under routine measurement conditions thereby providing the basis for an improved comparability of fluorescence measurements and eventually standardization. This first set of traceable fluorescence standards, which links fluorescence measurements to the spectral radiance scale in the spectral range of 300-770 nm and has been optimized for spectrofluorometers, can be employed for different measurement geometries and can be adapted to different fluorescence techniques with proper consideration of the underlying measurement principles.

Calibration↗

Role of the cardiac nerve in the effect of a novel innocuous stimulus on the heart rate of Megalobulimus mogianensis.

The effects of a brief jet of water delivered to the anterior portion of body-head on the heart rate of Megalobulimus mogianensis were determined in a group of intact snails (N = 8), previously prepared for electrocardiogram recording. The heart rate was significantly increased following stimulation. Nevertheless, with repetition of the stimulus there was a significant decrease in the magnitude of the heart rate variation and in the time for the basal heart rate to recover (first stimulus, 7.4 +/- 1.2 bpm and 15.5 +/- 1.8 min; second stimulus, 4.8 +/- 1.0 bpm and 10.6 +/- 1.5 min; third stimulus, 5.0 +/- 0.3 bpm and 11.1 +/- 1.8 min), indicating that this behavioral response undergoes early habituation. To determine the role of the cardiac nerve in mediating the heart rate alterations induced by the jet of water two other groups were tested: denervated animals (N = 8) and sham-operated control animals (N = 8). Although the innocuous stimulus caused the heart rate to increase significantly in both experimental groups, the mean increase in heart rate in denervated animals (3.2 +/- 0.4 bpm) was 41% of the value obtained in sham-operated animals (7.8 +/- 1.5 bpm), indicating that the cardiac nerve is responsible for 59% of the cardioacceleration induced by the innocuous stimulus. The increase in heart rate observed in denervated animals may be due to an increase in venous return promoted by the intense muscular activity associated with the retraction-protraction of the anterior part of the body induced by the jet of water.

Animals↗

Components to the acid-base related ventilatory drives in the South American lungfish Lepidosiren paradoxa.

Lungfish are closely related to terrestrial vertebrates (tetrapoda). Like tetrapods, the South American lungfish (Lepidosiren paradoxa) has central chemoreceptors involved in regulation of acid-base status. However, no data were available on peripheral CO(2)/[H(+)] receptors. Therefore, we tested the hypothesis that such receptors exist by measuring the ventilatory responses during a 5h exposure to combined aquatic/gas phase hypercarbia 7% (approximately 49 mmHg). Normocarbic control ventilation was 22 ml BTPS kg(-1)h(-1), and hypercarbia increased ventilation to 175 ml BTPS kg(-1)h(-1) at 5h. This procedure was repeated with the modification that normocarbic mock CSF (pH 7.45; P(CO2) = 20.7 mmHg) was applied to superfuse the cerebral ventricular system during the last 2h of the experiment. This served to eliminate the hypercarbic stimulus to the central chemoreceptors, while possible responses from peripheral chemoreceptors would remain intact. Peripheral receptors were detected, since ventilation became reduced to 62 ml BTPS kg(-1)h(-1) (P<0.05), which exceeds the initial normocarbic control ventilation (P<0.05). Based on this, the peripheral contribution accounted for 20% of the total response to hypercarbia, similar to the contribution of these receptors in man.

Acid-Base Equilibrium↗

Coherent inelastic light scattering from a microwave-excited array of magnetic particles.

Inelastic light scattering from an array of Permalloy particles driven by a microwave magnetic field is shown to be a coherent phenomenon in which the scattered radiation is observed only at diffraction angles corresponding to the reciprocal lattice of the array. The results are explained in terms of the phase coherence of the inelastically scattered light by each of the particles.

Journal Article↗

Focal myositis of the iliopsoas muscle--a benign pseudotumour: ultrasound appearance in correlation with CT and MRI.

OBJECTIVE: Focal myositis of the iliopsoas muscle is a rare condition. A case is presented, emphasizing the value of ultrasound for detection, localisation, image-guided biopsy and follow-up in correlation with CT and MRI findings. MATERIAL AND METHODS: A 58-year-old woman was referred to our clinic with strong left sided inguinal pain, which radiated to the thigh and had lasted for four days. Ultrasound, CT and MRI were performed. Ultrasound-guided biopsy with histological correlation was obtained and US-follow-ups were available. RESULTS: CT showed an enlarged iliopsoas muscle on the left side without any focal pathology or enhancement. MRI revealed a sharpely delineated lesion, which was hypointense to muscle in fat-suppressed T1 w images with circumferential enhancement and showed a hyperintense appearance in T2 w images. Ultrasound displayed a polylobulated, inhomogeneous and hypoechoic tumour within the iliopsoas muscle. Ultrasound-guided biopsy was found to be compatible with myositis. After oral therapy with steroids, improvement could be documented by serial ultrasound follow-up as the size of the tumour was definitely regressing. CONCLUSION: Focal myositis of the iliopsoas muscle is a rare entity which may mimic a tumoural lesion. Imaging findings may not be conclusive, and US-guided biopsy is recommended to rule out a malignant mass. Ultrasound seems to be the most cost-effective method for diagnosis, image guided biopsy and follow-up.

Adrenal Cortex Hormones↗

Agonistic-like responses from the torus semicircularis dorsalis elicited by GABA(A) blockade in the weakly electric fish Gymnotus carapo.

Findings by our group have shown that the dorsolateral telencephalon of Gymnotus carapo sends efferents to the mesencephalic torus semicircularis dorsalis (TSd) and that presumably this connection is involved in the changes in electric organ discharge (EOD) and in skeletomotor responses observed following microinjections of GABA A antagonist bicuculline into this telencephalic region. Other studies have implicated the TSd or its mammalian homologue, the inferior colliculus, in defensive responses. In the present study, we explore the possible involvement of the TSd and of the GABA-ergic system in the modulation of the electric and skeletomotor displays. For this purpose, different doses of bicuculline (0.98, 0.49, 0.245, and 0.015 mM) and muscimol (15.35 mM) were microinjected (0.1 microL) in the TSd of the awake G. carapo. Microinjection of bicuculline induced dose-dependent interruptions of EOD and increased skeletomotor activity resembling defense displays. The effects of the two highest doses showed maximum values at 5 min (4.3 +/- 2.7 and 3.8 +/- 2.0 Hz, P < 0.05) and persisted until 10 min (11 +/- 5.7 and 8.7 +/- 5.2 Hz, P < 0.05). Microinjections of muscimol were ineffective. During the interruptions of EOD, the novelty response (increased frequency in response to sensory novelties) induced by an electric stimulus delivered by a pair of electrodes placed in the water of the experimental cuvette was reduced or abolished. These data suggest that the GABA-ergic mechanisms of the TSd inhibit the neural substrate of the defense reaction at this midbrain level.

Animals↗

Chronomodulated chemotherapy with oxaliplatin, 5-FU and sodium folinate in metastatic gastrointestinal cancer patients: original analysis of non-hematological toxicity and patient characteristics in a pilot investigation.

OBJECTIVE: Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate. METHODS: Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity. CONCLUSION: The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.

Adult↗

Pharmacokinetics of oxaliplatin and non-hematological toxicity in metastatic gastrointestinal cancer patients treated with chronomodulated oxaliplatin, 5-FU and sodium folinate in a pilot investigation.

OBJECTIVE: To analyze in a pilot study the association between the pharmacokinetics of chronomodulated administered oxaliplatin and non-hematological toxicity in patients with metastatic gastrointestinal cancer. METHODS: 16 patients received a 4-day chemotherapeutic regimen consisting of a 12-h chronomodulated infusion of oxaliplatin (25 mg/m2) followed by a 12-h chronomodulated infusion of 5-fluorouracil (750 mg/m2) and sodium folinate (150 mg/m2) daily. Plasma pharmacokinetics of oxaliplatin, measured as ultrafiltrable platinum, were determined. RESULTS: Pharmacokinetics and non-hematological adverse events could be assessed in all patients included in the study. Pharmacokinetic parameters showed moderate interpatient variability. The occurrence of nausea and vomiting, but not diarrhea, was significantly associated with the pharmacokinetics of ultrafiltrable platinum. Thus, increased AUC values were observed in patients who experienced nausea or vomiting. No differences in pharmacokinetic parameters were found between patients with and without oxaliplatin-induced neurotoxicity or the other selected non-hematological toxicities. CONCLUSION: The preliminary results in this pilot study suggest an association between pharmacokinetics of ultrafiltrable platinum and non-hematological toxicity such as nausea and vomiting. Furthermore, although the sample size is limited, systemic exposure to ultrafiltrable platinum appears to predict the risk of non-hematological toxicity in patients treated with chronomodulated oxaliplatin combined with 5-FU and FS.

Adult↗

Critical considerations on the diagnostic appraisal, adaptation and remodelling of bone graft substitutes.

The diagnostic assessment of skeletal defects has a long-standing tradition. As a result of the development of new bone grafting materials, the demands on diagnostic assessment have also increased. The mode and quality of diagnostic appraisal are crucial to further clinical use and outcome prediction. Alongside traditional clinical and biological techniques, molecular biological methods have gained a broad scope of application and will be used even more frequently in the future.

Bone Substitutes↗

The ultrastructure and processing properties of Straumann Bone Ceramic and NanoBone.

The ultrastructure, fundamental chemistry, and processing modes of fully synthetic bone grafting materials are relevant to the reconstruction of osseous defects. Rapid progress in the profitable market of biomaterials has led to the development of various bone substitutes. Despite all these efforts, an ideal and full substitute of autologous bone is not yet in sight. With regard to anorganic calcium phosphate ceramics, Straumann Bone Ceramic and NanoBone are compared. These have a similar composition and are osteoconductive, which indispensably requires contact with well-vascularised bone.

Bone Substitutes↗

Effect of CO2 supply on formation of reactive oxygen species in Arabidopsis thaliana.

Light-induced generation of reactive oxygen species (ROS) in 2-week-old leaves of Arabidopsis thaliana was studied by means of the ROS-sensitive dyes nitroblue tetrazolium (NBT) and 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Superposition of pictures of chlorophyll fluorescence and DCF fluorescence indicated that the origin of ROS was in the chloroplasts. Experiments were done with zero, 0.1, or 10 mM NaHCO3 in the infiltration medium. Energy quenching in photosystem II was higher under low CO2 concentrations as measured by chlorophyll fluorescence. DCF fluorescence showed that CO2 deficiency led to an increase of ROS generation. In contrast, the photosystem II inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea reduced the light-induced increase of DCF fluorescence. This indicates that ROS production does not primarily result from over-reduction of photosystem II as caused by impeding electron flow in the electron transfer chain. More likely, it is an effect of diverting electron flux normally aimed at carboxylation in the Calvin cycle to other sinks more prone to the generation of toxic radicals. There was no significant effect of salicyl hydroxamate (a blocker of the alternative oxidase), showing that the mitochondrial electron transfer chain seems to play a minor role as already indicated by the superposition of chlorophyll and DCF fluorescence.

Arabidopsis↗