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Biomedical subjects

Ulrich Hoffmann

Publications and source records attributed to Ulrich Hoffmann.

At least 19 recordsLinked to original sources

Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease.

Patients with peripheral arterial disease (PAD) may develop a broad range of peripheral nerve dysfunctions including pain and sensory deficiencies due to chronic ischemia mostly involving the lower limbs. To investigate the degree of sensory abnormalities in such patients quantitative sensory testing (QST) might be a useful tool. Forty-five patients and 20 controls were enrolled in the present study and underwent QST according to the protocol of the German Research Network on Neuropathic Pain. PAD was graded according to the Rutherford classification. PAD patients were divided into two groups: 16 patients with critical limb ischemia (severe PAD) and 29 patients with intermittent claudication (moderate PAD). QST revealed impaired cold and warm detection, increased mechanical and vibration detection thresholds, and increased perceptual wind-up on the affected leg (all p<0.001). Paradoxical heat sensation (p<0.05) and dynamic mechanical allodynia (p<0.01) were also observed. Subgroup analysis of patients without diabetes (control n=20, moderate PAD n=21, severe PAD n=8) confirmed most of these findings. In patients with severe PAD, sensory deficits were more pronounced than in patients with moderate PAD and were detected even in the face. These data indicate that QST can detect sensory abnormalities in PAD patients. While the pattern of decreased perception suggests deafferentation for Abeta-, Adelta-, and C-fiber inputs, the presence of allodynia suggests that central sensitization also plays a role in the pain state of PAD patients. Subgroup analysis points towards a PAD-associated peripheral neuropathy independent of diabetes.

Aged↗

Clinical presentation and vascular imaging in giant cell arteritis of the femoropopliteal and tibioperoneal arteries. Analysis of four cases.

We present four patients with rapidly progressive claudication of the lower limbs due to extracranial giant cell arteritis. Additional findings suggestive of giant cell arteritis were involvement of the axillary or brachial arteries in two patients, symptoms of polymyalgia rheumatica or temporal arteritis in three, and all patients had severely elevated erythrocyte sedimentation rate and C-reactive protein level. Lower limb involvement affected preferentially the femoropopliteal, deep femoral, and tibioperoneal arteries. Hypoechogenic, concentric mural thickening suggestive of vasculitis was readily visible in all involved arterial segments by duplex ultrasound imaging, whereas angiography was rather unspecific. Typical changes for large-vessel vasculitis were also detectable by magnetic resonance imaging and fluorine-18-desoxyglucose positron emission tomography. More widespread use of these vascular imaging techniques may show that giant cell arteritis of the lower limbs is more frequent than previously assumed.

Aged↗

Organophosphate poisonings with parathion and dimethoate.

OBJECTIVE: Organophosphate toxicity is the leading cause of morbidity and death in poisoning by insecticides. The clinical symptoms of pesticide toxicity range from the classic cholinergic syndrome to flaccid paralysis and intractable seizures. The mainstays of therapy are atropine, oximes, benzodiazepines and supportive care. The toxicokinetics vary not only with the extent of exposure, but also with the chemical structure of the agent. PATIENTS: We report two cases of poisoning with parathion-ethyl and dimethoate. The patients developed a cholinergic syndrome immediately, accompanied by bradycardia and hypotension. INTERVENTIONS: The patients were admitted to the intensive care unit (ICU) a few hours after ingestion. Atropine was administered according to the cholinergic symptoms. The patients recovered in the ICU after 10-12 days and were discharged after 3 and 4 weeks. MEASUREMENTS AND RESULTS: Organophosphate blood and urine levels were determined on admission and during hospitalisation. The pesticides were rapidly distributed and slow elimination rate of the poisons was documented. In the case of parathion-ethyl the distribution half-life estimated was t(1/2alpha) = 3.1h while the terminal half-life was t(1/2beta) = 17.9 h. Using a one-compartment model for dimethoate the elimination half-life was t(1/2beta) = 30.4 h in plasma and 23.8 h in urine. The serum pseudo-cholinesterase activity was below the limit of detection at admission and recovered during the following 3weeks.

Aged↗

Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy.

OBJECTIVES: This study was designed to apply the rapid Elecsys S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys S100 immunoassay and compared to those obtained by the well-established LIA-mat S100 system. RESULTS: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys S100 system. CONCLUSIONS: The Elecsys S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.

Aged↗

From EEG dependency multichannel matching pursuit to sparse topographic EEG decomposition.

In this work, we present a multichannel EEG decomposition model based on an adaptive topographic time-frequency approximation technique. It is an extension of the Matching Pursuit algorithm and called dependency multichannel matching pursuit (DMMP). It takes the physiologically explainable and statistically observable topographic dependencies between the channels into account, namely the spatial smoothness of neighboring electrodes that is implied by the electric leadfield. DMMP decomposes a multichannel signal as a weighted sum of atoms from a given dictionary where the single channels are represented from exactly the same subset of a complete dictionary. The decomposition is illustrated on topographical EEG data during different physiological conditions using a complete Gabor dictionary. Further the extension of the single-channel time-frequency distribution to a multichannel time-frequency distribution is given. This can be used for the visualization of the decomposition structure of multichannel EEG. A clustering procedure applied to the topographies, the vectors of the corresponding contribution of an atom to the signal in each channel produced by DMMP, leads to an extremely sparse topographic decomposition of the EEG.

Algorithms↗

Comparison of angiography, duplex sonography and intravascular ultrasound for the graduation of femoropopliteal stenoses before and after balloon angioplasty.

The graduation of femoropopliteal stenoses by either digital subtraction angiography (DSA) or duplex sonography remains challenging, particularly after percutaneous transluminal angioplasty (PTA). More accurate assessment of stenosis might be achieved with intravascular ultrasound (IVUS). We investigated the relationship between DSA, IVUS and duplex before and after 32 femoropopliteal PTAs. Over the whole range of stenoses, peak systolic velocity (PSV) and peak velocity ratio (PVR) correlated better with DSA-stenosis (R(2) = .72 and 0.74, respectively, p < 0.01) than with IVUS-stenosis (R(2) = 0.58 and 0.50, p < 0.01). Within the subgroup of preinterventional (51 to 99%) stenoses, PVR was significantly correlated only with DSA-stenosis (R(2) = 0.60, p < 0.01). Severe dissection after PTA was associated with a disproportionate rise in PSV and large discrepancies between IVUS and DSA. Unexpectedly, our data show that intrastenotic flow acceleration assessed by duplex sonography correlates better with DSA- than with IVUS-stenosis. The concordance between duplex sonography, DSA and IVUS was particularly weak in postinterventional measurements, casting some doubt on the reliability of these methods for the assessment of residual stenosis after femoropopliteal PTA.

Angiography, Digital Subtraction↗

Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation.

Endothelial dysfunction caused by increases in vascular oxidant stress that decrease bioavailable nitric oxide (NO) plays a critical role in the vascular pathobiology of hyperhomocysteinemia. Boosting cellular glutathione levels or increasing the activity of cellular glutathione peroxidase can compensate for homocysteine's effects on endothelial function. Aged garlic extract (AGE) contains water- and oil-soluble sulfur compounds that modify the intracellular thiol and redox state, minimize intracellular oxidant stress, and stimulate NO generation in endothelial cells and animals. We performed a placebo-controlled, blinded, crossover trial to examine whether AGE reduces macro- and microvascular endothelial dysfunction during acute hyperhomocysteinemia induced by an oral methionine challenge in healthy subjects. Acute hyperhomocysteinemia leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular endothelial dysfunction. In addition, acute hyperhomocysteinemia leads to a decrease in acetylcholine-stimulated skin perfusion as measured by laser-Doppler flowmetry. This indicates microvascular endothelial dysfunction, which is presumably a result of impairment of the endothelium-derived hyperpolarizing factor pathway. Pretreatment with AGE for 6 wk significantly diminished the adverse effects of acute hyperhomocysteinemia in both vascular territories. We conclude that AGE may at least partly prevent a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor during acute hyperhomocysteinemia. This pilot study warrants further investigations on the effects of AGE on endothelial dysfunction in patients with other cardiovascular risk factors or established vascular disease and on the clinical outcome of patients with cardiovascular disease.

Biological Availability↗

Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition.

The multi-drug resistance protein 2 (MRP2; ABCC2) is an ATP-binding cassette transporter playing an important role in detoxification and chemoprotection by transporting a wide range of compounds, especially conjugates of lipophilic substances with glutathione, glucuronate and sulfate, which are collectively known as phase II products of biotransformation. In addition, MRP2 can also transport uncharged compounds in cotransport with glutathione, and thus can modulate the pharmacokinetics of many drugs. The other way around, its expression and activity are also altered by certain drugs and disease states. Unlike other members of the MRP/ABCC family, MRP2 is specifically expressed on the apical membrane domain of polarised cells as hepatocytes, renal proximal tubular cells, enterocytes and syncytiotrophoblasts of the placenta. Several naturally occurring mutations leading to the absence of functional MRP2 protein from the apical membrane have been described causing the human Dubin-Johnson syndrome associated with conjugated hyperbilirubinaemia. Experimental mutation studies have revealed critical amino acids for substrate binding in the MRP2 molecule. This review is, therefore, focused on the structure and function of MRP2, the substrates transported and the clinical relevance of MRP2.

Animals↗

Serum S-100B protein levels during and after successful carotid artery stenting or carotid endarterectomy.

PURPOSE: To characterize the course of S-100B serum levels, a reliable marker for cellular brain damage, in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA) for carotid artery stenosis compared to control groups undergoing hemithyroidectomy (HT) or coronary angiography (CA). METHODS: Forty-six consecutive patients scheduled for revascularization of internal carotid artery (ICA) stenosis were included in the study. Fourteen patients (11 men; median age 70 years, interquartile range [IQR] 63-74) were selected for treatment with CAS, while CEA was performed in 31 patients (24 men; median age 68 years, IQR 54-78) during the same time period. Fourteen consecutive patients (8 men; median age 60 years, IQR 48-70) undergoing CA for suspected coronary heart disease and 14 patients (10 women; median age 36 years, IQR 26-54) undergoing HT for a single thyroid nodule served as controls. RESULTS: All procedures were completed successfully. During ICA clamping in CEA patients without postoperative neurological deficits, median S-100B serum levels transiently increased from 0.04 to 0.26 ng/mL (p<0.01) and returned to baseline levels after declamping. Median S-100B serum levels of CAS patients without neurological impairment remained at baseline values. No increase in S-100B levels occurred in either control group. Three CEA patients who suffered from neurological deficits (1 transient ischemic attack and 1 major stroke) showed sustained elevation of S-100B serum levels 6 hours after extubation. CONCLUSION: In patients without neurological complications, CEA but not CAS was associated with a transient increase in the S-100B serum levels. Results indicate that the increase in S-100B does not originate from extracerebral sources, but rather appears to represent an impairment of the blood-brain barrier integrity or subtle brain cell damage probably due to hypoperfusion during clamping. Sustained elevation of S-100B serum levels corresponded to the development of postoperative neurological deficits.

Adult↗

The ABC transporters MDR1 and MRP2: multiple functions in disposition of xenobiotics and drug resistance.

ATP-binding cassette (ABC) transporters comprise one of the largest membrane bound protein families. They are involved in transport of numerous compounds. These proteins transport substrates against a concentration gradient with ATP hydrolysis as a driving force across the membrane. Mammalian ABC proteins have important physiological, pharmacological and toxicological functions including the transport of lipids, bile salts, drugs, toxic and environmental agents. The efflux pumps serve both as natural defense mechanisms and influence the bioavailability and disposition of drugs. In general terms, the transporters remove xenobiotics from the cellular environment. For example, in cancer cells, over expression of these molecules may confer to multidrug resistance against cytostatic drugs. In addition, based on diverse structural characteristics and a broad substrate specifity, ABC transport proteins alter the intracellular concentration of a variety of therapeutically used compounds and toxicologically relevant agents. We review the function of the human multidrug resistance protein MDR1, (P-glycoprotein, ABCB1) and the multidrug resistance protein MRP2 (ABCC2). We focus on four topics namely 1) structure and physiological functions of these transporters, 2) substrates e.g., drugs, xenotoxins, and environmental toxicants including their conjugates, 3) drug-drug interactions, and the role of chemosensitizers which may be able to reverse drug resistance, and 4) pharmacologically and toxicologically relevant genetic polymorphisms in transport proteins and their clinical implications.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Ultrasound assisted electrochemical oxidation of substituted toluenes.

Investigations on ultrasound assisted electrochemical syntheses demonstrate the positive influence of ultrasound on the achievable current density, selectivity and yield, but there is still a lack of investigations concerning the ultrasound influence on electroorganic syntheses. Especially the determining parameters like operation conditions and reactor geometry are not well defined for an industrial application. Therefore, the electrooxidation of substituted toluenes to their corresponding benzaldehydes via electrochemical conversion to the dialkylacetals, which is a reaction of great interest in industrial production, is studied with and without sonification of the working electrode. Experiments in a test-cell are done to evaluate the fundamental characteristics of the combined use of ultrasound and electrooxidation. A strong dependency of the current densities on the applied ultrasound power and a shift of oxidation potentials to lower values are achieved. Work is extended by theoretical investigations concerning the ultrasound field.For technical interesting syntheses a high electrode area-reactor volume ratio is demanded. This is achieved by an experimental sono-electrochemical gap cell with an electrode distance of only a few millimetres and a sound source "face on" the working electrode. Synthesis experiments done with this experimental set-up show an increase in chemical yield.

Journal Article↗

High-resolution MR imaging of human atherosclerotic femoral arteries in vivo: validation with intravascular ultrasound.

PURPOSE: To establish a magnetic resonance (MR) imaging protocol for noninvasive in-vivo analysis of atherosclerotic femoral artery segments in humans and to compare the results to those of intravascular ultrasonography (IVUS). MATERIALS AND METHODS: In seven patients with peripheral arterial occlusive disease, 20 femoral arterial segments per person were examined by high-resolution (HR) MR imaging and IVUS. Comparison was possible in 123 of 140 segments. MR imaging was performed at 1.5 T with use of a three-dimensional (3D) time-of-flight sequence with an in-plane resolution of 0.78 x 0.49 mm(2). 3D contrast-enhanced MR angiography was used for exact positioning of the HR MR imaging slices. IVUS (3.5 F, 40 MHz) was performed with use of a motorized pullback system. Parameters analyzed included cross-sectional lumen area (LA), vessel area (VA), and extent of vessel wall calcification. RESULTS: Agreement between IVUS and HR MR imaging was analyzed with use of the Bland-Altman method. The paired LA measurements were in close agreement: the Bland-Altman mean bias in LA was -0.4 mm with a precision of +/-5.1 mm (P =.062). As a result of dorsal echo extinction in IVUS, VA measurements were feasible in only 74 of 140 segments. VA measurements were moderately correlated (r = 0.74; P <.0001), and a 25% overestimation by HR MR imaging compared to IVUS was observed. Intra- and interobserver comparisons for LA and VA measured with HR MR imaging did not show significant differences. Vessel wall calcifications were classified with a sensitivity of 91%, a specificity of 93%, and an accuracy of 93%. CONCLUSIONS: The MR imaging protocol introduced in the present study permits precise assessment of LA and extent of calcification in peripheral arterial occlusive disease in vivo. HR MR imaging shows high concordance with IVUS and may have the potential for noninvasive therapy monitoring.

Angiography, Digital Subtraction↗

Roxithromycin treatment prevents progression of peripheral arterial occlusive disease in Chlamydia pneumoniae seropositive men: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Evidence has been provided that the atherosclerotic process may be associated with chronic infection with Chlamydia pneumoniae. The effect of antibiotic treatment on peripheral arterial occlusive disease has not been investigated yet. METHODS AND RESULTS: Forty C pneumoniae seropositive men suffering from peripheral arterial occlusive disease were randomly assigned to receive either roxithromycin (300 mg daily) or placebo for 28 days. During the 2.7-year follow-up, the number of invasive revascularizations per patient, the walking distance before intervention (in patients without intervention at study end), and the change of carotid plaque size were assessed. Five interventions were performed on 4 patients (20%) in the roxithromycin group, and 29 interventions were performed on 9 patients (45%) in the placebo group. Limitation of walking distance to 200 m or less was observed in 4 patients (20%) in the roxithromycin group and in 13 patients (65%) in the placebo group. The effect of macrolide treatment on the number of interventions per patient and on preinterventional walking distance was significant. Possible confounding variables such as classical vascular risk factors were excluded by multiple regression analyses. Carotid plaque areas monitored over 6 months decreased in the roxithromycin group (mean relative value, 94.4%) but remained constant in the placebo group (100.2%). Regression of carotid plaque size observed in roxithromycin-treated patients was significant for soft plaques. CONCLUSIONS: This study indicates that macrolide treatment for 1 month is effective in preventing C pneumoniae seropositive men from progression of lower limb atherosclerosis for several years.

Aged↗

Investigations on the energy conversion in sonochemical processes.

In the present work the energy transformation in sonochemical processes is studied by using electrical power measurement techniques and calorimetry. The influence of the ultrasonic amplitude and the properties of the irradiated medium on the efficiency of the equipment is shown. With increasing temperature and increasing solvent vapor pressure less energy can be brought into the fluid. More energy is consumed in high viscous media than in low viscous liquids. Finally the quality of calorimetry is discussed and a new energy-based efficiency factor for sonochemical processes is introduced.

Journal Article↗

Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia.

Mildly elevated plasma homocysteine levels are an independent risk factor for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulation. Endothelial dysfunction as manifested by impaired endothelium-dependent regulation of vascular tone and blood flow, by increased recruitment and adhesion of circulating inflammatory cells to the endothelium, and by a loss of endothelial cell antithrombotic function contributes to the vascular disorders linked to hyperhomocysteinemia. Increased vascular oxidant stress through imbalanced thiol redox status and inhibition of important antioxidant enzymes by homocysteine results in decreased bioavailability of the endothelium-derived signaling molecule nitric oxide via oxidative inactivation. This plays a central role in the molecular mechanisms underlying the effects of homocysteine on endothelial function. Supplementation of folic acid and vitamin B12 has been demonstrated to be efficient in lowering mildly elevated plasma homocysteine levels and in reversing homocysteine-induced impairment of endothelium-dependent vasoreactivity. Results from ongoing intervention trials will determine whether homocysteine-lowering therapies contribute to the prevention and reduction of atherothrombotic vascular disease and may thereby provide support for the causal relationship between hyperhomocysteinemia and atherothrombosis.

Arteriosclerosis↗