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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 19 recordsLinked to original sources

Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication.

BACKGROUND: This study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD). SUBJECTS AND METHODS: In 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication. RESULTS: In the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120-180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004). CONCLUSIONS: After fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

Adult↗

Sacroplasty by CT and fluoroscopic guidance: is the procedure right for your patient?

BACKGROUND AND PURPOSE: Sacral insufficiency fractures are an infrequent but often disabling cause of severe low back pain. We report our results of a sacroplasty technique, using CT for needle placement and fluoroscopy to monitor the polymethylmethacrylate injection in a group of patients with sacral insufficiency fractures. METHODS: All patients had a history of chronic back pain and had an osteoporotic sacral insufficiency fracture documented by imaging before the procedure. With the patient under conscious sedation, a bone biopsy needle was placed under CT guidance; the patient was then transferred to the fluoroscopy suite, where a polymethylmethacrylate mixture was injected into the sacrum under real-time fluoroscopy. Clinical outcome was assessed by telephone. RESULTS: The procedure was performed on 13 female patients with an average age of 76 years (range, 60-88 years). A bilateral procedure was performed in 11 patients and a unilateral procedure was performed in 2 patients. An average of 4.1 mL of cement was injected for each treatment. There were no instances of cement extravasation into the central canal or sacral foramina. Long-term follow-up, averaging 15 months, was available in 6 patients. Five patients (83%) reported no symptoms of pain at all. The final patient, in whom a bilateral procedure was performed, was completely asymptomatic on the left side but reported persistent unilateral pain on the right. CONCLUSION: Sacroplasty is a safe and effective procedure in the treatment of sacral insufficiency fractures that can provide substantial pain relief and lead to a better quality of life.

Aged↗

Measurement of the x-ray mass energy-absorption coefficient of air using 3 keV to 10 keV synchrotron radiation.

For the first time absolute photon mass energy-absorption coefficients of air in the energy range 3 keV to 10 keV have been measured with relative standard uncertainties less than 1%, significantly smaller than those of up to 5% assumed hitherto for calculated data. Monochromatized synchrotron radiation was used to measure both the total radiant energy by means of silicon photodiodes calibrated against a cryogenic radiometer and the fraction of radiant energy that is deposited in dry air by means of a free air ionization chamber. The measured ionization charge was converted into energy absorbed in air by calculated effective W values of photons as a function of their energy based on new measurements of the W values in dry air for electron kinetic energies between 1 keV and 7 keV, also presented in this work. The measured absorption coefficients were compared with state-of-the art calculations and found to agree within 0.7% with data calculated earlier by Hubbell at energies above 4 keV but were found to differ by values up to 2.1% at 10 keV from more recent calculations of Seltzer.

Air↗

18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa-associated lymphoid tissue: histology makes the difference.

BACKGROUND: The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is still a matter of debate, and conflicting results have been reported. We have evaluated whether the histological feature of plasmacytic differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma regarding 18F-FDG uptake. PATIENTS AND METHODS: A total of 35 patients with a diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F-FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake, standard uptake values (SUVs) were calculated. RESULTS: A total of 19 patients had MALT lymphoma with plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of 16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result. Two of these patients disclosed no tracer uptake in the majority of involved sites apart from one single lesions, while three had a true-positive 18F-FDG-PET scan (SUV: 3.4-6.0). CONCLUSIONS: 18F-FDG-PET visualizes pMALT in a high proportion of patients, whereas FDG-PET results are significantly less reliable in typical MALT (P = 0.001). This finding may partly account for the heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.

Adult↗

Global biodiversity conservation priorities.

The location of and threats to biodiversity are distributed unevenly, so prioritization is essential to minimize biodiversity loss. To address this need, biodiversity conservation organizations have proposed nine templates of global priorities over the past decade. Here, we review the concepts, methods, results, impacts, and challenges of these prioritizations of conservation practice within the theoretical irreplaceability/vulnerability framework of systematic conservation planning. Most of the templates prioritize highly irreplaceable regions; some are reactive (prioritizing high vulnerability), and others are proactive (prioritizing low vulnerability). We hope this synthesis improves understanding of these prioritization approaches and that it results in more efficient allocation of geographically flexible conservation funding.

Animals↗

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading.

BACKGROUND: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) has become a routine measure for staging and follow-up of patients with aggressive lymphoma. By contrast, its usefulness to visualize indolent lymphomas characterized by a lower cellular turnover has not clearly been defined. We have investigated accuracy and clinical usefulness of 18F-FDG-PET in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 64 patients with FL WHO grade I - III (48, 5, and 11 patients) were imaged at our institution to assess the value of 18F-FDG-PET for imaging of FL of different gradings. A total of 115 scans (48 before therapy and 67 for response assessment after treatment) were performed, and findings were compared to conventional staging including CT-scan of thorax and abdomen, sonography of lymph nodes and bone marrow biopsy. RESULTS: Overall, 18F-FDG-PET had a sensitivity of 98%, a specificity of 94%, a positive predictive value of 95% and a negative predictive value of 98%. These results were significantly more accurate (P = 0.023) than the conventional radiology studies. There was no significant difference (P = 0.093) in the accuracy between patients with indolent (WHO grade I and II) versus aggressive FL (WHO grade III). CONCLUSION: 18F-FDG-PET scan is a reliable method for staging and follow up of patients with nodal FL irrespective of tumor grading.

Adult↗

Toward theoretical analysis of long-range proton transfer kinetics in biomolecular pumps.

Motivated by the long-term goal of theoretically analyzing long-range proton transfer (PT) kinetics in biomolecular pumps, researchers made a number of technical developments in the framework of quantum mechanics-molecular mechanics (QM/MM) simulations. A set of collective reaction coordinates is proposed for characterizing the progress of long-range proton transfers; unlike previous suggestions, the new coordinates can describe PT along highly nonlinear three-dimensional pathways. Calculations using a realistic model of carbonic anhydrase demonstrated that adiabatic mapping using these collective coordinates gives reliable energetics and critical geometrical parameters as compared to minimum energy path calculations, which suggests that the new coordinates can be effectively used as reaction coordinate in potential of mean force calculations for long-range PT in complex systems. In addition, the generalized solvent boundary potential was implemented in the QM/MM framework for rectangular geometries, which is useful for studying reactions in membrane systems. The resulting protocol was found to produce water structure in the interior of aquaporin consistent with previous studies including a much larger number of explicit solvent and lipid molecules. The effect of electrostatics for PT through a membrane protein was also illustrated with a simple model channel embedded in different dielectric continuum environments. The encouraging results observed so far suggest that robust theoretical analysis of long-range PT kinetics in biomolecular pumps can soon be realized in a QM/MM framework.

Aquaporins↗

[Therapy of hypercalcemia with ibandronate in case of acute renal failure].

Hypercalcaemia is a common complication of malignancies associated with bone destruction. Besides, benign diseases as sarcoidosis or hyperparathyroidism may lead to hypercalcaemia. The main principles of modern therapy contain a forced diuresis as well as the application of bisphosphonates. Latter substances bear the danger of developing a renal insufficiency. Here, we report the case of a female patient, suffering from primary hyperparathyroidism with severe hypercalcaemia and calcium levels up to 6 mmol/l, who developed acute renal failure. We treated the patient with forced diuresis and repeated infusions of ibandronate (5 x 6 mg ibandronate). Even if lowering the serum levels of calcium only for a short time after each application, yet we could improve renal function by these means. Only after performing a parathyroidectomy, we could see a sustained decline of calcium levels. This case report supports the results of other publications, that have reported the missing nephrotoxic effect of ibandronate compared to other bisphosphonates.

Acute Kidney Injury↗

Risk communication in consultations about hormone therapy in the menopause: concordance in risk assessment and framing due to the context.

BACKGROUND: It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making. OBJECTIVE: The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition. METHODS: Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden. RESULTS: Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview. CONCLUSION: Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking.

Communication↗

In vitro hymenoptera venom allergy diagnosis: improved by screening for cross-reactive carbohydrate determinants and reciprocal inhibition.

BACKGROUND: Immunoglobulin (Ig) E-double positivity for honeybee (HB) and yellow jacket (YJ) venom causes diagnostic difficulties concerning therapeutical strategies. The aim of this study was to clarify the cause and relation of the cross-reactivity in patients with insect venom allergy. METHODS: For this purpose, 147 patients with suspected stinging insect allergy and CAP-FEIA-double positivity were investigated for specific sIgE to additional cross-reactive carbohydrate determinant (CCD)-containing allergens: timothy grass pollen, rape pollen, natural rubber latex (NRL), bromelain, and horseradish peroxidase (HRP). Sera with sIgE to NRL were further investigated with the commercially available recombinant latex allergens. Reciprocal inhibition assays with both venoms and HRP were performed. RESULTS: About 36 of 147 (24.5%) patients had sIgE to both venoms only. However, 111 of 147 (75.5%) additionally reacted to CCD-carrying allergens. 89 of 111 CCD-reactive sera had NRL-sIgE. In cases where inhibition experiments were performed, the NRL-sIgE binding was completely abolished in the presence of HRP. Only nine of 61 sera were positive for at least one recombinant latex allergen; all of them were negative in history and NRL-skin prick test. In 43 sera containing sIgE to CCD, HRP inhibition revealed unequivocal results: In 28 of 43 (65%) an HRP-inhibition >70% of sIgE to one venom occurred, pointing out the relevant venom. In three of 43 sIgE proved to be entirely CCD-specific. CONCLUSIONS: Our data indicate that in cases of IgE positivity to both insect venoms supplementary screening tests with at least one CCD-containing allergen should be performed; HRP being a suitable tool for this test. In addition, subsequent reciprocal inhibition is an essential diagnostic method to specify cross-reacting sIgE results.

Adolescent↗

Ultrafast relaxation in quasi-one-dimensional organic molecular crystals.

We present a comprehensive study of ultrafast relaxation properties of optical excitations in thin films of quasi-1D stacked organic materials PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) and MePTCDI (N,N'-dimethylperylene-3,4,9,10-dicarboximide) over five decades of time. Pump-probe experiments reveal excitonic intraband relaxation time constants of 65 fs for MePTCDI and 100 fs for PTCDA. The initial time-resolved luminescence anisotropy is consistent with the exciton model of Davydov-split states. The subsequent decay of the anisotropy can be explained with a thermally activated exciton hopping process. A full understanding of the pump-probe experiments calls for an explanation beyond the models presently available.

Journal Article↗

A critical evaluation of different QM/MM frontier treatments with SCC-DFTB as the QM method.

The performance of different link atom based frontier treatments in QM/MM simulations was evaluated critically with SCC-DFTB as the QM method. In addition to the analysis of gas-phase molecules as in previous studies, an important element of the present work is that chemical reactions in realistic enzyme systems were also examined. The schemes tested include all options available in the program CHARMM for SCC-DFTB/MM simulation, which treat electrostatic interactions due to the MM atoms close to the QM/MM boundary in different ways. In addition, a new approach, the divided frontier charge (DIV), has been implemented in which the partial charge associated with the frontier MM atom ("link host") is evenly distributed to the other MM atoms in the same group. The performance of these schemes was evaluated based on properties including proton affinities, deprotonation energies, dipole moments, and energetics of proton transfer reactions. Similar to previous work, it was found that calculated proton affinities and deprotonation energies of alcohols, carbonic acids, amino acids, and model DNA bases are very sensitive to the link atom scheme; the commonly used single link atom approach often gives error on the order of 15 to 20 kcal/mol. Other schemes give better and, on average, mutually comparable results. For proton transfer reactions, encouragingly, both activation barriers and reaction energies are fairly insensitive (within a typical range of 2-4 kcal/mol) to the link atom scheme due to error cancellation, and this was observed for both gas-phase and enzyme systems. Therefore, the effect of using different link atom schemes in QM/MM simulations is rather small for chemical reactions that conserve the total charge. Although the current study used an approximate DFT method as the QM level, the observed trends are expected to be applicable to QM/MM methods with use of other QM approaches. This observation does not mean to encourage QM/MM simulations without careful benchmark in the study of specific systems, rather it emphasizes that other technical details, such as the treatment of long-range electrostatics, tend to play a more important role and need to be handled carefully.

Journal Article↗

Calculating absorption shifts for retinal proteins: computational challenges.

Rhodopsins can modulate the optical properties of their chromophores over a wide range of wavelengths. The mechanism for this spectral tuning is based on the response of the retinal chromophore to external stress and the interaction with the charged, polar, and polarizable amino acids of the protein environment and is connected to its large change in dipole moment upon excitation, its large electronic polarizability, and its structural flexibility. In this work, we investigate the accuracy of computational approaches for modeling changes in absorption energies with respect to changes in geometry and applied external electric fields. We illustrate the high sensitivity of absorption energies on the ground-state structure of retinal, which varies significantly with the computational method used for geometry optimization. The response to external fields, in particular to point charges which model the protein environment in combined quantum mechanical/molecular mechanical (QM/MM) applications, is a crucial feature, which is not properly represented by previously used methods, such as time-dependent density functional theory (TDDFT), complete active space self-consistent field (CASSCF), and Hartree-Fock (HF) or semiempirical configuration interaction singles (CIS). This is discussed in detail for bacteriorhodopsin (bR), a protein which blue-shifts retinal gas-phase excitation energy by about 0.5 eV. As a result of this study, we propose a procedure which combines structure optimization or molecular dynamics simulation using DFT methods with a semiempirical or ab initio multireference configuration interaction treatment of the excitation energies. Using a conventional QM/MM point charge representation of the protein environment, we obtain an absorption energy for bR of 2.34 eV. This result is already close to the experimental value of 2.18 eV, even without considering the effects of protein polarization, differential dispersion, and conformational sampling.

Absorption↗

Thermodynamics of membrane elasticity--a molecular level approach to one- and two-component fluid amphiphilic membranes, part I: theory.

The present publication provides a detailed theoretical approach to the elastic properties of one- and two-component amphiphilic membranes. It is formulated in terms of the molecular free energy aiming at an application to molecular models. The work focuses on the bending elastic moduli and the difference between the condition of constant surface tension and constant chemical potentials. It is found that the bending modulus of mean curvature becomes negative for two-component membranes approaching the limit of phase separation at constant chemical potentials. The treatment of bilayer membranes explicitly integrates monolayer-monolayer coupling. This is beneficial for the assessment of coupling effects for specific molecular models. The article is completed by a comprehensive continuum mechanical description of one-component monolayers. Based on the generalized Laplace equation it is suggested that a simultaneous excess of oil and water is likely to preclude the existence of non-cylindrical bicontinuous phases.

Computer Simulation↗

Thermodynamics of membrane elasticity--a molecular level approach to one- and two-component fluid amphiphilic membranes, part II: applications.

The theoretical framework developed in the accompanying publication is applied to a number of experimentally relevant amphiphilic systems. These include the influence of thermodynamic conditions and non-ideal mixing on bending elasticity, ellipsoidal modes of microemulsions and vesicles, hydrocarbon chain coupling in bilayers and the effect of osmotic and hydrostatic pressure on inverse hexagonal (H(II)) phases. It is found that the bending moduli at constant surface tension and constant chemical potentials are markedly different only for two-component membranes and non-ideal mixing with a tendency towards phase separation. The results indicate that non-ideal mixing is the main reason behind the experimentally observed strong compositional dependence of membrane elasticity. It is generally recommended to prefer the bending elastic moduli at constant chemical potentials to those at constant surface tension. A comparison between the area-difference-elasticity (ADE) model and explicit free energy calculations using a molecular model shows a good qualitative agreement for the sphere-to-ellipsoid transition of vesicles. Results for different free energy models of the hydrocarbon chains of amphiphilic molecules suggest that monolayer-monolayer chain coupling is responsible for the relatively higher bending stiffness of bilayers compared to single monolayers. For H(II)-phases an instability at negative pressure differences is predicted.

Computer Simulation↗

[Diagnosis and interventional therapy for ductal gallstones].

Different imaging modalities recently underwent considerable improvements for the visualization of ductal gallstones. The declining significance of endoscopic retrograde cholangiopancreatography (ERCP) has been accepted unanimously. This paradigm shift is mostly due to improvements in transabdominal ultrasound, the increased availability of endoscopic ultrasound, and the use of magnetic resonance cholangiopancreatography (MRCP). In particular, MRCP is limited only in visualizing very small intraductal gallstones due to spatial resolution restrictions, whereas the detection rate of larger concretions is comparable to that with ERCP and endoscopic ultrasound. Patients with biliary pancreatitis benefit greatly from noninvasive MRCP visualization, establishing it as the preferred imaging modality. Particularly if ductal gallstones requiring further intervention are highly suspected, ERCP is preferable to other imaging modalities. If that suspicion is moderate, MRCP would be the imaging modality of choice, and transabdominal ultrasound would be performed if ductal gallstones are considered improbable. In up to 90% of cases, removal can be achieved endoscopically. Using a percutaneous approach smaller concretions can be extracted directly. However, larger gallstones need to be broken down into smaller fragments. For lithotripsy, either cholangioscopically-guided laser or electrohydraulic procedures are easy and effective. In case of strictures due to biliodigestive anastomoses, additional papillary balloon dilatation may be required.

Cholangiopancreatography, Endoscopic Retrograde↗

Recombinant activated factor VII and the anaesthetist.

Recombinant activated factor VII is a safe and effective for the treatment and prevention of haemorrhage in haemophiliacs with circulating inhibitors to replacement factors, and patients with Glanzmann's thrombasthenia refractory to platelet transfusion. By restoring thrombin generation on the surface of tissue factor bearing cells, such as activated platelets and monocytes, recombinant activated factor VII has the potential to effect haemostasis in the setting of many coagulopathic states encountered by the anaesthetist in the operating theatre or the intensive care unit. Case reports of successful rescue therapy make up the majority of the literature covering other, numerous, off-label uses of recombinant activated factor VII, although some randomised, controlled studies, mostly underpowered to address safety concerns, have been performed. However, off-label use is becoming increasingly popular judging by the number of published case reports. Additional randomised, controlled trials to determine the safe and appropriate use of this potentially valuable therapy in broader patient groups are eagerly awaited.

Blood Loss, Surgical↗

Motor aprosodia due to isolated brainstem stroke in a young woman.

A 21 year old woman presented with coma and quadriparesis secondary to bilateral pontine infarction. Three weeks later motor aprosodia was the most notable neurological finding apart from mild asymmetric limb weakness. No other supratentorial lesion was noted on initial and subsequent multimodality magnetic resonance imaging and magnetic resonance perfusion imaging revealed right frontotemporal hypoperfusion. This is the first report of aprosodia with an isolated brainstem lesion.

Adult↗