[A different kind of wrestler's ear]. / Das Ringerohr der etwas anderen Art.

We report the case of a 19-year-old patient who presented with recurrent circular and scaly skin changes. The patient reported wrestling as his main leisure activity. After an unsuccessful attempt at local antibiotic treatment, detailed dermatological work-up revealed the skin changes to be tinea corporis gladiatorum. According to dermatological guidelines for dermatophytosis, systemic treatment with fluconazole and local ointments containing ciclopirox olamine and ketoconazole were administered, which rapidly led to significant improvement.

[Influence of external and endogenous factors on cervical lymph nodes : Sonographic study of size and morphology]. / Einfluss externer und endogener Faktoren auf Halslymphknoten : Sonographische Untersuchung der Größe und Morphologie.

BACKGROUND: Sonographic evaluation of the dignity of cervical lymph nodes is essential for further diagnostics and treatment concepts in various diseases. The aim of this prospective monocenter study was to determine the sonomorphology and size of benign changes of lymph nodes in healthy subjects and patients who had undergone surgery, in order to examine the influence of various factors. MATERIALS AND METHODS: Data from 205 healthy subjects and 15 patients before and after surgery were analyzed. Sonographically representative lymph nodes were measured in diameter and volumes were calculated; margins, the recognizability of a hilus, and vascularization were documented. A detailed medical history was taken using a standardized questionnaire. RESULTS: In 20-39-year-olds, lymph node diameters were larger than in 40-59- and over 60-year-olds, and in 40-59-year-olds, the lymph nodes were larger than over 60-year-old subjects. Individuals with consumption of less than 10 and 10-20 cigarettes per day showed larger cervical lymph nodes compared to subjects with a consumption of more than 20 cigarettes per day. Smokers who additionally exercised routinely showed larger lymph nodes than those who never smoked or exercised. In addition, we observed that both the size and the number of cervical lymph nodes increased postoperatively compared to preoperative. CONCLUSION: The recorded lymph nodes corresponded to the established sonographic criteria of benign lymph nodes. Our results show that age, smoking intensity, combination of smoking with sporting activity, and surgery influence the size of sonographically measured cervical lymph nodes.

[Satisfaction of patients with tracheostomal epithesis]. / Die Tracheostomaepithese - eine Evaluation der Patientenzufriedenheit.

BACKGROUND: The utilization of craniofacial prosthesis has proven to be very successful for craniofacial defects. However, there is a lack of knowledge about the value of an epithesis for voice rehabilitation in patients with tracheostomy. The aim of this study was to describe application of the tracheostomy epithesis and to present a systematic analysis of the functional results of this prosthetic technique. MATERIALS AND METHODS: This retrospective analysis included 48 patients on follow-up being treated in three different centers after laryngectomy and/or tracheostomy between 2008 and 2014. Subjects were given a questionnaire with items such as speech quality, quality of life, free hand speech ability, respiratory quality and sufficient tracheostomal sealing comparing values before and after application of an individually custom-made tracheostomy epithesis. Twenty-eight answered the questionnaire and could be reported. RESULTS: Twenty-eight of 48 patients were consistently being included in follow-up. The statistical analysis revealed a significant improvement of tracheostoma occlusion (p < 0.05) and improvement in free hand speech ability (p < 0.05). A leakage of air during voice production could be prevented in 59.3% after application of an epithesis. Quality of life correlated directly with successful utilization of an epithesis. CONCLUSION: In the literature, different industrialized products are described to realize occlusion of the tracheostoma for sufficient speech production without using the hands. In numerous cases commercial solutions fail and the patients need individual modifications. Our study first describes the evaluation of custom-made tracheostomal epithesis. From our observed results we advocate the individual tracheostomal epithesis as a durable solution for voice rehabilitation.

Preloading with L-tyrosine increases the uptake of boronophenylalanine in mouse melanoma cells.

To improve the effectiveness of boron neutron capture therapy, the possibility of stimulating boron uptake was investigated in an experimental model. B16F1 mouse melanoma cells were exposed to boronophenylalanine (BPA). The intracellular boron concentration followed Michaelis-Menten kinetics in the early incubation phase. In the late phase, cellular boron concentration was linearly related to the BPA concentration in the culture medium. Incubation with L-tyrosine before exposure to BPA (preloading) increased the intracellular boron concentration by a factor of three. It is concluded that in B16F1 cells BPA is transported by L and presumably ASC (alanine, serine, and cysteine) transport systems, and that boron uptake can be effectively stimulated by L-tyrosine preloading.

Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: a randomized dose-response trial.

OBJECTIVES: This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia. BACKGROUND: Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase. METHODS: Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables. RESULTS: After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B. CONCLUSIONS: Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.

Imaging techniques in the analysis of brain function and behaviour.

Techniques such as positron-emission tomography, single-photon-emission computed tomography, functional magnetic-resonance imaging and magnetoencephalography permit the observation of biological processes in the brain in a noninvasive manner. They have yielded new insights into the biological interrelations of sensory, motor and cognitive functions, as well as into brain diseases. Combined use of these techniques may provide more information than just the sum of its constituents, and this may narrow the gap between the biological data provided by these techniques and the mental models described by clinicians, mathematicians, psychologists and philosophers.

Increased deoxyribonucleic acid synthesis of autonomously functioning thyroid adenomas: independent of but further stimulable by thyrotropin.

The percentage of cells in the S/G2M fraction and the cytosol deoxythymidine kinase activity (TKA) were measured in autonomously functioning thyroid adenomas (AFTA) and paranodular tissue (PNT), with special regard to the impact of the patient's serum TSH concentration on DNA synthesis. The S/G2M fraction was determined by means of DNA flow cytometry, and TKA was determined by radioenzyme assay. The S/G2M fraction of AFTA (n = 15, median; 7.1%; range, 3.2-9.2%) exceeded the S/G2M fraction of normal thyroid tissue (n = 8; median, 2.8%; range, 2.3-4.0%; P = 0.008) and in 12 of 13 AFTA was 1.2- to 2.3-fold higher than the S/G2M fraction in the corresponding PNT (median, 4.0%; range, 2.5-6.7%; P = 0.0022). TKA of AFTA (n = 15; median, 681 microIU/mg; range, 432-854 microIU/mg) exceeded TKA of normal thyroid tissue (n = 8; median, 356 microIU/mg; range, 194-426 microIU/mg; P = 0.0001) and was 1.1- to 4.2-fold increased compared with TKA activity in the corresponding PNT (median, 430 microIU/mg; range, 162-570 microIU/mg; P = 0.001). In the absence of measurable serum TSH there was a constant increase in the S/G2M fractions and the TKA in AFTA vs. those in PNT. In patients treated with methimazole with serum TSH concentrations of 0.5 mIU/L or more, the S/G2M fraction and TKA in both AFTA and PNT were significantly higher than those in untreated patients with serum TSH concentrations of 0.5 mIU/L or less. In the majority of AFTA, functional autonomy and increased DNA synthesis are concomitant phenomena. Although TSH may stimulate DNA synthesis in both AFTA and PNT, measurable serum TSH concentrations are apparently not essential for DNA synthesis.

Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia.

BACKGROUND: Conditioning processes have been proposed to play a role in the development of anxiety disorders. As yet, the neurobiologic correlates of emotional learning have not been fully understood in these patients. Accordingly, brain activity was studied in subcortical and cortical regions involved in the processing of negative affect during differential aversive classical conditioning. METHODS: Twelve patients with social phobia and 12 healthy control subjects were presented with paired conditioned (CS; neutral facial expressions) and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional magnetic resonance imaging (fMRI) was utilized to examine regional cerebral activity during habituation, acquisition,a nd extinction trials. Activity was measured with echo-planar-imaging (EPI), and signal intensity in individually defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional valence to the CS indicated that behavioral conditioning occurred in both groups. The presentation of CS associated with negative odor led to signal decreases in the amygdala and hippocampus of normal subjects, whereas an opposite increased activation in both regions was observed in patients. Regional differences were not found during habituation and extinction. CONCLUSIONS: Results suggest that conditioned aversive stimuli are processed in subcortical regions, with phobic patients differing from control subjects.

Imaging muscarinic cholinergic receptors in human brain in vivo with Spect, [123I]4-iododexetimide, and [123I]4-iodolevetimide.

A method to image muscarinic acetylcholine receptors (muscarinic receptors) noninvasively in human brain in vivo was developed using [123I]4-iododexetimide ([123I]IDex), [123I]4-iodolevetimide ([123I]ILev), and single photon emission computed tomography (SPECT). [123I]IDex is a high-affinity muscarinic receptor antagonist. [123I]ILev is its pharmacologically inactive enantiomer and measures nonspecific binding of [123I]IDex in vitro. Regional brain activity after tracer injection was measured in four young normal volunteers for 24 h. Regional [123I]IDex and [123I]ILev activities were correlated early after injection, but not after 1.5 h. [123I]IDex activity increased over 7-12 h in neocortex, neostriatum, and thalamus, but decreased immediately after the injection peak in cerebellum. [123I]IDex activity was highest in neostriatum, followed in rank order by neocortex, thalamus, and cerebellum. [123I]IDex activity correlated with muscarinic receptor concentrations in matching brain regions. In contrast, [123I]ILev activity decreased immediately after the injection peak in all brain regions and did not correspond to muscarinic receptor concentrations. [123I]IDex activity in neocortex and neostriatum during equilibrium was six to seven times higher than [123I]ILev activity. The data demonstrate that [123I]IDex binds specifically to muscarinic receptors in vivo, whereas [123I]ILev represents the nonspecific part of [123I]IDex binding. Subtraction of [123I]ILev from [123I]IDex images on a pixel-by-pixel basis therefore reflects specific [123I]IDex binding to muscarinic receptors. Owing to its high specific binding, [123I]IDex has the potential to measure small changes in muscarinic receptor characteristics in vivo with SPECT. The use of stereoisomerism directly to measure nonspecific binding of [123I]IDex in vivo may reduce complexity in modeling approaches to muscarinic acetylcholine receptors in human brain.

Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects.

Accuracy in in vivo quantitation of brain function with positron emission tomography (PET) has often been limited by partial volume effects. This limitation becomes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with different degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume. GM PET was applied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetected in the PET image before correction for partial volume effects. In computer simulations, errors in the segmentation of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate determination of the actual radiotracer concentration in human brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM.

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.

High resolution SPECT in small animal research.

Single Photon Emission Computed Tomography (SPECT) is a technique used to assess physiological and biochemical processes under in vivo conditions. SPECT generates tomographic images from blood flow, glucose metabolism and receptor characteristics using radioactively labelled substances. This paper reviews the state of the art of in vivo imaging of laboratory animals in modified human and dedicated animal SPECT scanners. SPECT cameras with special collimators currently reach spatial resolutions up to 1 mm and sensitivities of about 1000 cps/MBq, allowing observation of receptor activity concentration changes in the pico-mole range. The time resolution of such cameras strongly depends on the pharmacological behaviour of the tracer and can range from several minutes to hours. Within these limits the functional characterization of many processes is possible. SPECT also offers the possibility to set up dynamic study protocols and repeated measurements of the same animal. This technique reduces the need for sacrificing animals, as was commonly practiced before the development of animal cameras. Animal SPECT gives the opportunity to monitor physiological and biochemical processes in animals in vivo, without interfering with the system under observation, and may become a valuable adjunct to the instrumentation (autoradiography, in vitro methods) of animal research.

Intensity coding of auditory stimuli: an fMRI study.

The effect of stimulus intensity (sound pressure level, SPL) of auditory stimuli on the BOLD response in the auditory cortex was investigated in 14 young and healthy subjects, with no hearing abnormalities, using echo-planar, functional magnetic resonance imaging (fMRI) during a verbal and a non-verbal auditory discrimination task. The stimuli were presented block-wise at three different intensities: 95, 85 and 75 dB (SPL). All subjects showed fMRI signal increases in superior temporal gyrus (STG) covering primary and secondary auditory cortex. Most importantly, the spatial extent of the fMRI response in STG increased with increasing stimulus intensity. It is hypothesized that spreading of excitation is associated with the encoding of increasing stimulus intensity levels. In addition, we found bifrontal activation supposedly evoked by the auditory-articulary loop of working memory. The results presented here should assist in the design of optimal activation strategies for studying the auditory cortex with fMRI paradigms and may help in understanding intensity coding of auditory stimuli.

Functional anatomy of intrinsic alertness: evidence for a fronto-parietal-thalamic-brainstem network in the right hemisphere.

Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Calculation of relative biological effectiveness for proton beams using biological weighting functions.

PURPOSE: The microdosimetric weighting function approach is used widely for beam comparison studies. The suitability of this model to predict the relative biological effectiveness (RBE) of therapeutic proton beams was studied. The RBE(alpha) (i.e., linear approximation) dependence on the type of biological end point, initial proton energy, energy spread of the input proton beam, and depth of beam penetration was investigated. METHODS AND MATERIALS: Proton transport calculations for a proton energy range from 70 to 250 MeV were performed to obtain proton energy spectra at a given depth. The corresponding microdosimetric distributions of lineal energy were calculated. To these distributions the biological response function approach was applied to calculate RBE(alpha) the biological effectiveness based on a linear dose-response relationship. The early intestinal tolerance assessed by crypt regeneration in mice and the inactivation of V79 cells were taken as biological end points. RESULTS: The RBE(alpha) values approach about 1 in the plateau region and gradually increase with the proton penetration depth. In the center of the Bragg peak, at the maximum dose delivery, the values of RBE(alpha) range from 1.1 (250-MeV beam, early intestinal tolerance in mice) to 1.9 (70-MeV beam, Chinese hamster V79 cells in G1/S phase). Distal to the Bragg peak, where only a small fraction of dose is delivered, the RBE(alpha) was found to be even higher. For modulated proton beams we found an increasing RBE(alpha) with depth in the spread-out Bragg peak (SOBP). Values up to 1.37 at the distal end of the SOBP plateau (155-MeV beam, SOBP between 5.3 and 13.2 cm) were obtained. CONCLUSION: More experimental work on the determination of microdosimetric weighting functions is needed. The results of the presented calculations indicate that for therapy planning it may be necessary to account for a depth dependence on proton RBE, especially for lower energy.

Assessment of brain muscarinic acetylcholinergic receptors in living mice using a simple probe, [125I]-4-iododexetimide and [125I]-4-iodolevetimide.

This study describes assessment of brain muscarinic acetylcholinergic receptors in living mice using a single-crystal radiation detection system, the high-affinity antagonist [125I]-4-iododexetimide, and the inactive enantiomer [125I]-4-iodolevetimide. Kinetics of radioligand binding, as well as perturbation by atropine displacement, can be determined using this simple probe technique.

High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult. Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory pediatric diseases permitted comparison of the precision of biopsy amyloid diagnosis in six different laboratories (labs), which applied the following methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red and electron microscopy (Lab 2), or Congo red and immunohistochemistry using monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this study based on the presence of amyloid in at least one biopsy. Whereas massive or no amyloid was concordantly recognized by all labs in 18 biopsies from nine patients, discordance was demonstrated in 14 biopsies from eight patients. Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when only minute amounts of amyloid were present. Had our technique (Lab 3) been available at the time of biopsy, amyloid could have been diagnosed years earlier, thereby sparing the patient further biopsies and allowing initiation of earlier treatment before organ damage could occur.