MRI of cystic fibrosis lung manifestations: sequence evaluation and clinical outcome analysis.

AIM: To evaluate different magnetic resonance imaging (MRI) sequences for diagnosis of pulmonary manifestations of cystic fibrosis (CF) in comparison to chest computed tomography (CT), including an extended outcome analysis. MATERIALS AND METHODS: Twenty-eight patients with CF (15 male, 13 female, mean age 30.5±9.4 years) underwent CT and MRI of the lung. MRI (1.5 T) included different T2- and T1-weighted sequences: breath-hold HASTE (half Fourier acquisition single shot turbo spin echo) and VIBE (volumetric interpolated breath-hold examination, before and after contrast medium administration) sequences and respiratory-triggered PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) sequences with and without fat signal suppression, and perfusion imaging. CT and MRI images were evaluated by the modified Helbich and the Eichinger scoring systems. The clinical follow-up analysis assessed pulmonary exacerbations within 24 months. RESULTS: The highest concordance to CT was achieved for the PROPELLER sequences without fat signal suppression (concordance correlation coefficient CCC of the overall modified Helbich score 0.93 and of the overall Eichinger score 0.93). The other sequences had the following concordance: PROPELLER with fat signal suppression (CCCs 0.91 and 0.92), HASTE (CCCs 0.87 and 0.89), VIBE (CCCs 0.84 and 0.85) sequences. In the outcome analysis, the combined MRI analysis of all five sequences and a specific MRI protocol (PROPELLER without fast signal suppression, VIBE sequences, perfusion imaging) reached similar correlations to the number of pulmonary exacerbations as the CT examinations. CONCLUSION: An optimum lung MRI protocol in patients with CF consists of PROPELLER sequences without fat signal suppression, VIBE sequences, and lung perfusion analysis to enable high diagnostic efficacy and outcome prediction.

Biofeedback of baroreflex sensitivity in patients with mild essential hypertension.

An attempt was made to reduce blood pressure by increasing the baroreflex sensitivity (BRS) via biofeedback. Six patients with mild essential hypertension and 5 normotensive participants were studied during 8 biofeedback sessions. Each session consisted of 5 trials, 5 min each. The first and the last trials served as baselines of heart rate, blood pressure, respiration, and BRS. During the 3 middle trials the BRS was calculated online using the sequencing technique. The resulting value was used as a visual analogue feedback signal. Participants were asked to increase BRS. The mean BRS was 8.3 [ms/mmHg] for the hypertensive patients and 12.2 [ms/mmHg] for the normotensive participants. During biofeedback trials as well as across sessions neither the hypertensive nor the normotensive group showed a statistically significant increase of BRS, only heart rate variability increased significantly. Contrary to expectation blood pressure increased in both groups. One hypertensive subject made significant progress during the training by performing valsalva maneuvers. The data show that BRS is reduced in hypertensive subjects. The increase of the heart rate variability could be a sign of the activation of the baroreflex although the BRS itself did not increase. Despite the successful technical and organizational implementation of this biofeedback approach, it was not effective to systematically reduce blood pressure. A further development in the direction of guiding the patient to use the valsalva breathing pattern and/or a prolonged duration of the biofeedback training might be promising.

Mechanism of Tet repressor induction by tetracyclines: length compensates for sequence in the alpha8-alpha9 loop.

Natural Tet repressor (TetR) variants are alpha-helical proteins bearing a large loop between helices 8 and 9, which is variable in sequence and length. We have deleted this loop consisting of 14 amino acid residues in TetR(D) and rebuilt it stepwise with up to 42 alanine residues. All except the mutant with the longest alanine loop show wild-type repression, but none is inducible with tetracycline. This demonstrates the importance of the alpha8-alpha9 loop and its amino acid sequence for induction. The induction efficiencies increase with loop length, when the more tightly binding inducer anhydrotetracycline is used. The largest increase of inducibility was observed for TetR mutants with loop lengths between eight and 17 alanine residues. Since loop residues Asp/Glu157 and Arg158 are conserved in the natural TetR sequence variants, we constructed a mutant in which all other residues of the loop were replaced by alanine. This mutant exhibits increased anhydrotetracycline induction compared to the corresponding alanine variant. Thus, these residues are important for induction. Binding constants for the anhydrotetracycline-TetR interaction are below the detection level of 10(5) M(-1) for the mutant with a loop of two alanine residues and increase sharply until a loop size of ten residues is reached. TetR variants with longer loops have similar anhydrotetracycline-binding constants, ranging between 2.6 x 10(9) M(-1) and 8.0 x 10(9) M(-1), about 500-fold lower than wild-type TetR. The increase of the affinity occurs at shorter loop lengths than that of inducibility. We conclude that the induction defect of the polyalanine variants arises from two increments: (i) the loop must have a minimal length-to allow efficient inducer binding; (ii) the loop must structurally participate in the conformational change associated with induction.

Proprioception in somatoform disorders.

20 patients with somatoform disorders as defined by DSM-IV and 20 healthy controls were examined for their proprioception. Several psychophysiological theories of somatoform disorders suggest biased proprioceptive abilities. The primary question is, whether we may find an inaccurate myogen perception in somatization as suggested by the approach of Bischoff or a more precise proprioception as may be derived from concepts of a higher awareness of body reactions. Furthermore it is expected, that somatoform patients perceive their muscle tension more intensely than do healthy subjects. Proprioceptive abilities were tested using a visual EMG biofeedback task. Resulting objective data and subjective ratings were analyzed within a psychophysiological regression approach which allows one to estimate the reliability, precision and intensity of proprioception. Results revealed that somatoform subjects demonstrated a more precise but not a more intense perception of muscle tension than did healthy controls.

Tet repressor induction without Mg2+.

We have examined anhydrotetracycline (atc) binding to Tet repressor (TetR) in dependence of the Mg(2+) concentration. Of all tc compounds tested so far, atc has the highest affinity for TetR, with a K(A) of 9.8 x 10(11) M(-1) in the presence of Mg(2+) and 6.5 x 10(7) M(-1) without Mg(2+). Thus, it binds TetR with 500-fold higher affinity than tc under both conditions. The Mg(2+)-free binding of atc to TetR leads to induction in vitro, demonstrating that the metal is not necessary to trigger the associated conformational change. To obtain more detailed information about Mg(2+)-free induction, we constructed and prepared to homogeneity four single-alanine substitution mutants of TetR. Three of them affect residues involved in contacting Mg(2+) (TetR H100A, E147A, and T103A), and one altered residue contacts tc TetR N82A. TetR H100A and E147A are induced by atc, with and without Mg(2+), showing 110-fold and 1000-fold decreased Mg(2+)-dependent and unchanged Mg(2+)-independent atc binding, respectively. Thus, the contacts of these residues to Mg(2+) are not necessary for induction. TetR N82A is not inducible under any of the conditions employed and shows an about 4000-fold decreased atc binding constant. The Mg(2+)-dependent affinity of TetR T103A for atc is only 400-fold reduced, but no induction with atc was observed. Thus, Thr103 must be essential for the conformational change associated with induction in the absence of Mg(2+).

Implicit memory for auditorily presented threatening stimuli: a process-dissociation approach.

The investigation of unconscious cognition involves especially problems with the methodology of measuring implicit and explicit proportions of different task performances. In this study the process dissociation procedure of Jacoby and its modification within the multinomial modelling framework for an indirect word-nonword-discrimination task is applied to a sample of 45 healthy students. The paradigm includes acoustically presented stimuli. During a learning phase, subjects listened to a series of neutral and threatening words. Performance was tested by letting subjects decide whether a presented stimulus (masked with white noise at signal-noise ratio of -17 dB or unmasked) had been a word or a nonword. Within this paradigm, implicit cognition occurs when (a) a word is more probably correctly recognized as "word" after presentation during the learning phase (typical priming effect) or when (b) a nonword derived from a word is more probably falsely recognized as "word" after its corresponding word had been presented during the learning phase (effect of implicit cognition given perceptual fluency). Frequencies for hits and false alarms were analyzed within the multinomial model which allows estimating parameters for the correct discrimination of words (c), the response bias (b), the classical priming effect (u1), and the parameter for the priming effect of "old" nonwords (u2). Under masked stimuli the multinomial model showed implicit cognition, an effect not equally found for neutral and threatening words. Threatening words exhibited a significantly higher portion of implicit cognition than neutral ones. Given the statistical complexity of multinomial models, the application of this method was explained in detail.

A synthetic inhibitor of factor Xa, DX-9065a, reduces proliferation of vascular smooth muscle cells in vivo in rats.

The effect of factor Xa inactivation on the proliferation of vascular smooth muscle cells in vivo was investigated in an experimental restenosis model in rats by using the direct factor Xa inhibitor DX-9065a. In the left common carotid artery, an injury of the vascular endothelium was produced by four external vessel clamps for 60 minutes. After 14 days, 3H-labeled methyl thymidine and 5-bromo-2'-deoxyuridine, respectively, were injected intraperitoneally. After 24 hours, both the left (damaged) and right (nondamaged) carotid arteries were removed, and the incorporation of 3H-methyl thymidine/microg protein was determined. For morphological analysis, the cells were labeled with hematoxylin as well as 5-bromo-2'-deoxyuridine. Stained vascular smooth muscle cell nuclei were counted, and the proliferation index (percentage of 5-bromo-2'-deoxyuridine-positive nuclei to total nuclei stained with hematoxylin) was determined. An external damage of the carotid artery induced proliferation of vascular smooth muscle cells and formation of a neointima within 2 weeks after vessel injury. As compared with control animals, single subcutaneous injection of DX-9065a (2.5, 5, and 10 mg/kg) given 30 minutes before vessel injury significantly reduced the incorporation of 3H-methyl thymidine/microg protein and the total cell number, as well as the proliferation index. The antiproliferative action of DX-9065a was not dose dependent in the range from 2.5 to 10 mg/kg s.c. A combination of bolus injection (5 mg/kg s.c.) with continuous administration (5 mg/kg/d s.c. for 7 and 14 days, respectively) did not increase the antiproliferative effect of DX-9065a. The results indicate a role of factor Xa in the complex pathogenesis of restenosis and the usefulness of a highly effective and selective inhibitor of factor Xa to inhibit proliferative processes.

Quantitative analysis of gene expression with an improved green fluorescent protein. p6.

The fast and easy in vivo detection predestines the green fluorescent protein (GFP) for its use as a reporter to quantify promoter activities. We have increased the sensitivity of GFP detection 320-fold compared to the wild-type by constructing gfp+, which contains mutations improving the folding efficiency and the fluorescence yield of GFP+. Twelve expression levels were measured using fusions of the gfp+ and lacZ genes with the tetA promoter in Escherichia coli. The agreement of GFP+ fluorescence with beta-galactosidase activities was excellent, demonstrating that the gfp+ gene can be used to accurately quantify gene expression in vivo. However, expression of the gfp+ gene from the stronger hsp60 promoter revealed that high cellular concentrations of GFP+ caused an inner filter effect reducing the fluorescence by 50%, thus underestimating promoter activity. This effect is probably due to the higher absorbance of cells containing GFP+. Thus promoters with activities differing by about two orders of magnitude can be correctly quantified using the gfp+ gene. Possibilities of using GFP variants beyond this range are discussed.

Relevance of muscular sensitivity, muscular activity, and cognitive variables for pain reduction associated with EMG biofeedback in fibromyalgia.

18 patients suffering from primary fibromyalgia received nine training sessions using EMG biofeedback over a period of four weeks. Pre- and posttreatment measurement of the baseline EMG activity of the trapezius, muscular sensitivity, and cognitive variables (helplessness and belief of control) were taken. Analysis indicated a significant reduction occurred in general intensity of pain and in EMG activity as well as a significant increase in muscular sensitivity. Multiple regression analyses indicated that the increase in muscular sensitivity correlated with the decrease of EMG activity in the trapezius baseline. Self-reported pain reduction was predicted by a change in cognitive variables.

[What can pain diaries achieve? Advantages and limitations of their use with reference to single case evaluation.]. / Was leisten Schmerztagebücher? : Vorzüge und Grenzen ihrer Anwendung unter besonderer Berücksichtigung einzelfallbezogener Auswertung.

Pain diaries are modern evaluation instruments for assessment of pain dynamics and treatment outcome. There are syndrome-specific and non-syndrome-specific diaries. They exist as paper-and-pencil versions, as electronic diaries or as uptime recorders. Pain diaries are especially suitable for considering pain course over time. There-fore, they have many fields of application, which extend to the topography, differential diagnosis, therapeutic evaluation, classification, indications and, obviously, to questions of research. A particular advantage of pain diaries is the possibility of individual design and realization. Despite numerous advantages, problems with the application and data analysis of diaries must be kept in mind. They are instruments with a large potential reactivity of measurements, e.g. answer tendencies, memory effects, simulation. In addition, items in pain diaries usually have different scale levels, which can lead to problems in adaequate analyses of data. The data analysis of pain diaries is demonstrated with the help of selected individual cases. Three different phases are distinguished, and useful suggestions for analysis of individual cases are submitted. The first evaluation step includes the visual inspection of primary data. This provides a survey of the process of pain and at the same time a reference level for assessment of the secondary data. The secondary data can be divided into agglomeration, variation and correlation data. Agglomeration data, such as frequencies, sums or means, are a first quantitative, but still superficial, process of analysis. Additionally, the findings should be complemented by variation data to characterize these results with regard to their variability. The significance of deviation measures is demonstrated by a selected case example. A small deviation in this case reveals a relatively constant course of pain parameters, whereas large deviation reflects an unstable course. Moreover, the variability of data can be analysed by trend coefficient and time series analysis. Time-related measures of deviation, developed in the 1930s by von Neumann et al., and a simple version of time-series analyses developed by Tryon, are described and compared with one another. Finally, the use of correlation statistics is useful to reveal important relationships between secondary data. For the case example such statistically significant relations exist between pain intensity, therapeutic interventions, and sleep duration. Due to the effort required by diary analysis the use of pain diaries seems to be indicated only if there is the intention to generate quantitative data by mathematical-statistical methods. Problems arise, in spite of the quantitative data level, from the limited comparability of results and the undeniable reactivity of measurements. At present open questions refer to the desirable or non-desirable stability of surveys by means of pain diaries and the possible generation of secondary effects as the result of long-term diary recording.

[Pain description and illness behavior in pain diaries of fibromyalgia and polyarthritis patients]. / Schmerzdeskription und Krankheitsverhalten in Schmerztagebüchern von Fibromyalgie- und Polyarthritis-Patienten.

Intensity, sensory-discriminative and affective-motivational quality of pain were assessed over a period of 14 days by means of the Bonn Pain Diary in 16 fibromyalgia (FM) patients and 18 rheumatoid arthritis (RA) patients. Additionally, patients reported pain and sleep duration, daily iratations, and pain-reducing interventions. FM patients differed from RA-patients by higher scores in the sensoric-discriminative component of pain. The patterns of preferred pain descriptors were syndrome-specific. However, the two groups did not differ in the overall daily pain duration; whereas in RA-patients the pain attacks occurred mostly until 10 a.m. In FM-patients, the time-course of pain over 14 days showed higher variability compared to RA-patients. RA patients sleep longer than FM-patients. Furthermore, the groups differ statistically significantly with respect to interactions of scaled pain with the preferred interventions in order to reduce pain. Conclusions concerning pain-referring cognitions are drawn. In general, the evaluation of self-reports about pain by behavioral parameters is recommended.

[Evaluating the validity of short witness reports using behavioral and psychophysiologic parameters]. / Glaubhaftigkeitsbeurteilung von kurzen Zeugenaussagen mittels behavioraler und psychophysiologischer Parameter.

Within the context of credibility assessment, the impact of behavioral and physiological adaptation and response patterns of truly and falsely testifying eyewitnesses was examined in a laboratory study. It was further examined statements concerning characteristics of the delict and the experimental situation itself. 20 subjects were instructed to truly or falsely testify after having witnessed a willful destruction. Eye movements, respiration, heart rate and skin conductance were recorded and analyzed by computer. Witnesses instructed to falsely testify showed elevated skin conductance responses and an increased variability of horizontal eye movements at the beginning of the session. Additionally, they also showed stronger responses in eye-blink rate, respiration rate and variability of skin conductance and heart rate to questions related to the behavior in the experimental situation. Reactivity to questions concerning the culprit was less pronounced. Results are discussed in terms of their application within the German law system.

[What do pain scales measure in patients with rheumatoid arthritis?]. / Was messen schmerzskalen bei patienten mit rheumatoider arthritis?

In this study carried out in a sample of 80 patients suffering from rheumatoid arthritis (RA) tried an attempt was made to answer the following questions: 1. are there pain factors with a wider range that are more generally applicable than those covered by current German questionnaires? 2. To what extent can somatic parameters predict pain factors? 3. To what extent can a patient's pain behavior (a patient's activity scores) predict pain factors? The study was based on data collected by means of the Pain Experience Questionnaire (PEQ), the McGill Pain Questionnaire MPQ, the West Haven-Yale Multidimensional Pain Inventory WHYMPI, the Measurement Of Patient Outcome Scale MOPO, as well as six different clinical parameters. By means of factor analysis, two second-order factors were extracted, representing 1. the patient's impairment due to intensive pain and 2. socio-emotional consequences of pain. At a statistically significant level, the first factor can be predicted by the clinical variables. Regression of the activity scores on the factor "socio-emotional consequences" suggests a close correlation between the two variables, although the results failed to reach statistical significance. On the whole, the results strongly support the notion of integrating clinical, behavioral and cognitive findings in the diagnostic assessment of chronic rheumatoid pain patients.

[The significance of stressful life events and their management in patients with rheumatoid arthritis, essential hypertension and stomach and duodenal ulcer]. / Zur Bedeutung belastender Lebensereignisse und deren Bewältigung bei Patienten mit rheumatoider Arthritis, essentieller Hypertonie und Ulcus ventriculi et duodeni.

In a multivariate approach critical life events and coping in 126 patients with rheumatoid arthritis, hypertension and gastrointestinal ulcers as well as healthy persons are researched with regard to their nosological meaning and their relationship to relevant clinical parameters. They answered a multi-dimensional coping questionnaire and an inventory which measures and evaluates individual relevant life events. With regard to this, different clinical information war processed. On the basis of the above named parameters, the four groups could be distinguished from one another. The interrelationship between psychosocial variables and clinical indices can be neglected.

[An integrated method of pain measurement based on Tursky's pain perception profile, for use in patients with progressive systemic sclerosis.]. / Multimethodale Schmerzmessung mit Hilfe des Pain Perception Profile von Tursky bei Patienten mit progressiv-systemischer Sklerose.

Tursky's pain perception profile [16] has been revised and adapted for use in German-speaking conditions, and this new modification is presented. It integrates six different methods of clinical and experimental methods of clinical and experimental pain measurement, which are intended to meet the enhanced demands put forward in pain research for multivariate measurement of pain by a variety of methods. The methods used are: (1) classification of three pain-related descriptive statements as they apply to the individual case; (2) use of these descriptive statements to keep a record in the form of a pain diary; (3) experimental determination of thermal pain thresholds; (4) determination of the behavior expressing the perception of thermal pain; (5) determination of sensitivity to pain by means of a standardized system for the estimation of the magnitude of thermal stimuli; and (6) in parallel with determination of the pain threshold and estimation of the magnitude of the stimulus, derivation of peripheral physiological parameters and the formulation of conclusions about the individual's way of handling pain. The various methods of investigation are presented, and results obtained with them in patients with chronic pain and in healthy volunteers are compared. The results document the many aspects of chronic pain and the necessity for multimodal measurement. In addition, they supply a means of achieving a better pain-related classification of pain patients on an experimental basis.

[Marital, family and sexual therapy with special reference to cognitive behavioral orientation]. / Ehe-, Familien- und Sexualtherapie mit besonderer Berücksichtigung kognitiv-behavioraler Orientierung.

This paper gives a review of relevant details characterizing procedures in marital and family therapy. They are described by means of "coalition strivings of therapy's participants", "reciprocal attribution of faults", "therapeutic motivation", "resistance" and "expectations to the therapy". In the main chapter, frequently discussed and applied concepts of marital and family therapy are systematized and illustrated by selected examples whereby a cognitive-behavioral perspective is dominating. In presenting intervention methods of marital therapy, especially operative procedures are discussed. In an excursus, a sexual therapeutic strategy as specification of marital therapeutic treatment goals is described. Finally, the author refers to organizational aspects of particular therapeutic sessions and to the rationale of therapist's behavior.

Functional irregularities of short-term and long-term memory storage in patients with Parkinson's disease and Huntington's disease.

Memory performance of Parkinson's disease patients (PD patients). Huntington's disease patients (HD patients) and healthy subjects were compared by a single-trial free recall task following the presentation of a stimulus list consisting of 30 nouns. The patient groups were categorized according to the severity of the disease into mild, moderate, and severe. Healthy subjects reproduced significantly more words than PD and HD patients, while the two patient groups did not differ in the total number of words reproduced. The differences between healthy and demented subjects are attributed to the impaired functional capacity of long-term memory; there were significant differences between healthy subjects and patients as well as between PD and HD patients. When taking the severity of the disease into consideration, varied influence on the capacity of long-term memory for PD and HD patients was found. Concerning short-term memory, neither a difference between healthy subjects and patients nor between both patient groups could be established. An effect of the severity of the disease could not be proven.

[Marital feedback behavior: relations between feedback activity of the partner and feedback quality, duration of the marriage and ability of the marriage to function]. / Eheliches Feedback-Verhalten: Beziehungen zwischen Feedback-Aktivität der Partner und Feedback-Qualität, Ehedauer und Funktionsfähigkeit der Ehe.

The effect of the quality of feedback and the feedback activity of partners on the feedback behavior of married controls, who differed with regard to the duration and the functioning of their marriages, was investigated. 106 married couples were divided into a group of disturbed marriages in the first half of life (GJE), a group of disturbed marriages in the second half of life (GAE), and harmonious marriages (HAE). During a conflict-conversation that was structured according to the technique of revealed differences the partners exchanged positive and negative feedback optically and acoustically. Corresponding to the frequency of the feedback active and less active partners were differentiated. In comparison with the couples of the HAE group, couples of the GAE group gave less feedback, especially less positive feedback. The less active partner of the GAE group gave significantly more negative feedback than the comparable partner of the HAE group. Differences between the GAE and the GJE group that can be called statistically significant do not exist. The results have been discussed with respect to their application.

Memory performance in Huntington's disease.

In this study the influence of special memory tasks, the effect of cues and the influence of the severity of the disease on the performance of short-term memory of patients suffering from Huntington's disease was examined. Stimulus material consisted of 30 nouns for reproduction and 20 nouns to be subsumed to 5 categories. Depending on experimental condition, assistance was given or withheld. 16 healthy subjects and 48 patients suffering from Huntington's disease took part in the study. Between these groups there was a significant effect of the factor "memory task." Furthermore, it could be demonstrated that the performance level decreases and differences between individuals increase with increasing severity of the disease. There was no significant effect of the factor "cues."