Interaction of somatoform and vestibular disorders.

BACKGROUND: The high coincidence of organic vestibular and somatoform vertigo syndromes has appeared to support pathogenic models showing a strong linkage between them. It was hypothesised that a persisting vestibular dysfunction causes the development of anxiety disorders. OBJECTIVE: To determine the relation between vestibular deficits and somatoform vertigo disorders in an interdisciplinary prospective study. METHODS: Participants were divided into eight diagnostic groups: healthy volunteers (n=26) and patients with benign paroxysmal positioning vertigo (BPPV, n=11), vestibular neuritis (n=11), Menière's disease (n=7), vestibular migraine (n=15), anxiety (n=23), depression (n=12), or somatoform disorders (n=22). Neuro-otological diagnostic procedures included electro-oculography with rotatory and caloric testing, orthoptic examination with measurements of subjective visual vertical (SVV) and ocular torsion, and a neurological examination. Psychosomatic diagnostic procedures comprised interviews and psychometric instruments. RESULTS: Patients with BPPV (35.3%) and with vestibular neuritis (52.2%) had pathological test values on caloric irrigation (p<0.001). Otolith dysfunction with pathological tilts of SVV and ocular torsion was found only in patients with vestibular neuritis (p<0.001). Patients with Menière's disease, vestibular migraine, and psychiatric disorders showed normal parameters for vestibular testing but pathological values for psychometric measures. There was no correlation between pathological neurological and pathological psychometric parameters. CONCLUSIONS: High anxiety scores are not a result of vestibular deficits or dysfunction. Patients with Menière's disease and vestibular migraine but not vestibular deficits showed the highest psychiatric comorbidity. Thus the course of vertigo syndromes and the possibility of a pre-existing psychopathological personality should be considered pathogenic factors in any linkage between organic and psychometric vertigo syndromes.

Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity.

BACKGROUND: Chronic urticaria (CU), one of the most common skin disorders, is characterized by spontaneous recurrent bouts of weals and pruritus and associated with severely impaired quality of life (QoL). OBJECTIVES: To determine what aspects of life quality are affected and to characterize the factors that impact on QoL in CU patients. SUBJECTS AND METHODS: This interdisciplinary interview/questionnaire-based study included 100 patients admitted to a University Hospital Dermatology Department for the identification of underlying causes of CU; 96 healthy subjects matched for age and sex were used as controls. QoL was assessed using Skindex-29, a validated instrument to measure the effects of skin disease on overall QoL (composite score) and three defined QoL aspects (emotions, symptoms, functioning). RESULTS: CU patients exhibited markedly reduced overall QoL compared with healthy control subjects. CU had distinct effects on the three QoL aspects assessed (functioning = emotions > symptoms). The age or sex of patients, the absence or presence of angio-oedemas, and the duration or cause of CU did not significantly influence QoL impairment. Interestingly, psychiatric comorbidity (depression, anxiety, somatoform disorders) was associated with a more pronounced reduction of QoL compared with CU patients without a psychiatric diagnosis and the severity of psychiatric disease was found to correlate with QoL impairment. CONCLUSIONS: Our data confirm that overall QoL is markedly reduced in CU patients. Social functioning and emotions were found to be the areas of QoL most affected in CU patients. Psychiatric comorbidity significantly increased QoL impairment, whereas QoL in CU patients was not significantly affected by age or sex, the absence or presence of angio-oedema, or the course or cause of CU.

Anxiety disorders and other psychiatric subgroups in patients complaining of dizziness.

Two hundred and two consecutive patients with dizziness were evaluated using blind neuro-otological testing and examination, blind psychiatric examination, including structured interviews (according to DSM-IV), the Symptom Check-List (SCL 90 R), and the State-Trait Anxiety Inventory (STAI). In 28% of the patients (N=50) dizziness was of organic origin (O group); in 55.3% (N=99) of psychogenic origin (P group) and in 16.8% comorbid psychiatric disorders were found (Mixed group). In 5.3% (N=10) neither organic nor psychiatric results could be found, which could explain the dizziness (Ideopathic group). Compared with the Organic group the patients with psychiatric disorders (P and Mixed group) had much more extensive workups for dizziness, intense emotional distress (anxiety, depression), greater handicaps, and high somatization scores. In the P and Mixed groups three main subgroups of psychiatric disorders could be found: anxiety (N=56), depressive (N=20), and somatoform disorders (N=53). Patients with anxiety and depressive disorders showed the greatest emotional distress and handicaps. The results indicate that psychiatric disorders, above all anxiety disorders, should be included in the differential diagnosis in patients with a long duration of dizziness and great handicaps. An interdisciplinary treatment (including psychiatric treatment) would be superior to an exclusive somatic one.

Clinical assessment of HIV-associated lipodystrophy syndrome: bioelectrical impedance analysis, anthropometry and clinical scores.

BACKGROUND: Diagnosis of the HIV-associated lipodystrophy syndrome is based on clinical assessment, in lack of a consensus about case definition and reference methods. Three bedside methods were compared in their diagnostic value for lipodystrophy. PATIENTS AND METHODS: Consecutive HIV-infected outpatients (n=278) were investigated, 128 of which also had data from 1997 available. Segmental bioelectrical impedance analysis (BIA) and waist, hip and thigh circumferences were performed. Changes in seven body regions were rated by physicians and patients using linear analogue scale assessment (LASA). Diagnostic cut-off values were searched by receiver operator characteristics. RESULTS: Lipodystrophy was diagnosed in 85 patients (31%). BIA demonstrated higher fat-free mass in patients with lipodystrophy but not after controlling for body mass index and sex. Segmental BIA was not superior to whole body BIA in detecting lipodystrophy. Fat-free mass increased from 1997 to 1999 independent from lipodystrophy. Waist-hip and waist-thigh ratios were higher in patients with lipodystrophy. BIA, anthropometry and LASA did not provide sufficient diagnostic cut-off values for lipodystrophy. Agreement between methods, and between patient and physician rating, was poor. CONCLUSION: These methods do not fulfil the urgent need for quantitative diagnostic tools for lipodystrophy. BIA estimates of fat free mass may be biased by lipodystrophy, indicating a need for re-calibration in HIV infected populations.

Time-course analysis of type II cell hyperplasia and alveolar bronchiolization in rats treated with different particulates.

In this study, we compared the morphological reaction patterns in rat lungs following a single intratracheal instillation of 20 mg quartz, 20 mg coal mine dust (15.3% quartz), or 25 mg talc. Control animals received a single dose of 0.5 ml saline solution intratracheally. Investigations by light microscopy, morphometry, and DNA image cytometry were carried out 3, 6, 12, and 18 mo after dust administration. During the investigation period, we observed a temporary increase in the number, area, and proliferative activity of the type II cells, which differed in intensity among the three dusts. After 18 mo, however, type II cells in treated animals did not differ from control animals. On the other hand, the expansion of a multifocal alveolar bronchiolization as putative preneoplastic lesion had progressed enormously by the end of the test (1-3% of the investigated lung area). Consistent with this, the proliferative activity of the epithelial cells in terminal bronchi of the coal mine dust- and quartz-treated animals was enhanced by the end of the 18-mo investigation period, while the reaction to talc was minimal (0.2% of totally investigated lung area). Our data suggest that in bronchiolo-alveolar regions, especially in the epithelium of terminal bronchi, there is an overshoot regeneration after cell damage that leads to an alveolar bronchiolization.

Stabilization of mutant 46-kDa mannose 6-phosphate receptors by proteasomal inhibitor lactacystin.

Palmitoylation of cysteine residue 34 within the 67-amino acid cytoplasmic domain of the 46-kDa mannose 6-phosphate receptor (MPR 46), which may be anchored to the lipid bilayer, prevents the receptor from entering lysosomes (Schweizer, A., Kornfeld, S., and Rohrer, J. (1996) J. Cell Biol. 132, 577-584). In the present study, we examined the importance of the spacing between the transmembrane domain and the palmitoylation anchor site in the cytoplasmic domain for stability and trafficking of MPR 46. MPR 46 mutants with deletions of residues 20-23 and 24-29 expressed in baby hamster kidney cells were rapidly degraded with half-lives of less than 10 h. The replacement of residues 24-29 by alanine resulted in prolongation of receptor stability (t(1)/(2) approximately 20 h). Whereas mutant MPR 46 could not be detected in lysosomal fractions and inhibitors of lysosomal proteases failed to prevent degradation, treatment with the proteasome inhibitor lactacystin resulted in increased stability of mutant MPR 46. Pulse-chase experiments at low temperature and the acquirement of endoglucosaminidase H-resistant oligosaccharides indicate that the majority of mutant MPR 46 is degraded after leaving the Golgi compartment. Altered trafficking of mutant MPR 46 may be the result of decreased palmitoylation reaching 40% of wild type receptors. The data suggest that the spacing between the transmembrane domain and the proposed palmitoylation anchor site in the cytoplasmic domain of MPR 46 is important for a post Golgi sorting step preventing receptor degradation by multiple proteolytic systems including the proteasome.

Mouse insulin-like growth factor binding protein-6: expression, purification, characterization and histochemical localization.

The mitogenic and metabolic activities of insulin-like growth factors (IGF) are modulated by a family of six high affinity IGF binding proteins (IGFBPs). This study describes the expression of the mouse IGFBP-6 which is unique among IGFBPs in its preferential binding of IGF II, in insect cells using the baculovirus system. The purified, O-glycosylated IGFBP-6 was functional as shown by IGF binding and by inhibition of IGF II-stimulated DNA synthesis in human fibroblasts. Specific antibodies generated in chicken against the recombinant IGFBP-6 were used for Western blotting analysis and immunohistochemistry. Strong immunoreactivity was found in ossifying bones of the cranial base, in cell clusters of the pancreas anlage, in the trigeminal ganglion, on myoblasts, on motoneurons of the spinal cord of embryonic mice. In tissues of adult mouse, strong IGFBP-6 immunostaining was present in epidermal and peridermal layers of the skin, in meningeal layers, in long-striated skeletal muscle, and in the Langerhans' islets of the pancreas. No immunopositive staining was observed in lung and liver indicating that sites of synthesis and IGFBP action are different.

Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is required for transport to the plasma membrane in Madin-Darby canine kidney and mouse fibroblast cells.

Up to 4% of the human 46-kDa mannose 6-phosphate receptor (MPR46) expressed in Madin-Darby canine kidney (MDCK) cells are localized at the cell surface. At steady state, the expression of MPR46 on the apical surface of filter-grown MDCK cells is about sixfold lower than on the basolateral surface. The cytoplasmic domain of the MPR46 is phosphorylated on serine 56 at low stoichiometry. By expressing mutant MPR46 we have shown that the MPR46 phosphorylation site is required for delivery to the plasma membrane. In addition, mutant MPR46 expressed in MPR-deficient mouse embryonic fibroblasts were not detected at the cell surface and their ability to sort newly synthesized cathepsin D was not altered. Since the loss of MPR46 phosphorylation correlates with the lack of cell surface expression, phosphorylation of serine 56 may either function as a direct plasma membrane targeting signal or inhibit MPR46 recycling from endosomes to Golgi, resulting in trafficking to the cell surface.

How good are patients with panic disorder at perceiving their heartbeats?

Palpitations are among the most common symptoms of panic attacks. The present review addresses the question of whether systematic differences in heartbeat perception exist between patients with panic disorder and control subjects. Paradigms involving the comparison of heartbeat sensations with external signals such as discrimination task have failed to find group differences. Recent improvements in methodology may give clearer results in future studies. The majority of studies using the mental tracking paradigm have shown that panic disorder patients show a better heartbeat perception than controls. Discrepant results are probably related to different instructions and differences in sample characteristics such as the inclusion of patients on medication affecting the cardiovascular system. More accurate heartbeat perception, may, however, be restricted to those patients who show agoraphobic avoidance behavior. It is also conceivable that group differences in the mental tracking paradigm are due to attentional biases or a tendency to interpret weak sensations as heartbeats rather than differences in perceptual sensitivity. More ambulatory studies are needed to test whether the results can be generalized to the patients' natural environment. So far ambulatory studies have established superior heartbeat perception only in the subgroup of panic disorder patients with cardiac neurosis. A 1-year prospective study showed that heartbeat perception as assessed with the mental tracking paradigm predicted maintenance of panic attacks. This supports the clinical significance of the findings. Increased cardiac awareness may increase the probability of anxiety-inducing bodily sensations triggering the vicious cycle of panic. Laboratory and ambulatory monitoring studies showed that panic disorder patients respond with anxiety when they think that their heart rate has accelerated. Increased cardiac awareness may also contribute to the maintenance of the disorder by motivating the patients to avoid situations in which these sensations occur.

[Anticoagulation after vascular surgery interventions]. / Antikoagulation nach gefässchirurgischen Interventionen.

Questionnaires regarding postoperative antiplatelet and anticoagulant therapy were answered by personal interviews with 35 German vascular surgeons. A 3/4 majority follow the recommendations of literature by anticoagulation after embolectomy in patients with persistent atrial fibrillation. Antiplatelet therapy is common in patients after thrombendarteriectomy and justified by improving the natural history of atherosclerotic disease. Considerable differences exist in postoperative therapy following peripheral bypass surgery. Controlled clinical trials are rare and present contradicting results. Prospective randomized multicenter studies are necessary.

Heartbeat perception and panic disorder: possible explanations for discrepant findings.

Results on cardiac awareness in panic disorder are inconsistent. The present study attempted to clarify whether differences in instructions or the inclusion of patients taking antidepressant medication could account for these inconsistencies. 112 patients with panic disorder with agoraphobia were compared to 40 normal controls on the heartbeat perception task developed by Schandry (1981) [Schandry, R., Psychophysiology, 18, 483-488] using a standard instruction ("count all heartbeats you feel in your body") and a strict instruction ("count only those heartbeats about which you are sure"). Superior heartbeat perception for patients was only found with the standard instruction. Similarly, only with the standard instruction, patients taking medication affecting the cardiovascular system performed worse than patients without medication, as expected based on the relationship between stroke volume and heartbeat perception. The pattern of group differences indicates that agoraphobic patients have a better feeling for how fast their heart is beating than controls although these differences may be due to a tendency to interpret weak sensations as heartbeats. Furthermore, we tested in a subgroup of 40 patients whether cardiac awareness changes with exposure treatment. No changes in heartbeat perception were observed.

Increased cardiac awareness in panic disorder.

We investigated cardiac perception in panic disorder with both self-report and objective measures. In Study 1, 120 patients with panic disorder, 86 infrequent panickers, and 38 patients with other anxiety disorders reported greater cardiac and gastrointestinal awareness than 62 normal control subjects. Subjects with panic attacks reported greater cardiac awareness, but not gastrointestinal awareness, than those with other anxiety disorders. Studies 2 and 3 included a test of heart rate perception in which subjects silently counted their heart-beats without taking their pulse. In Study 2, 65 panic disorder patients showed better performance than 50 infrequent panickers, 27 patients with simple phobias, and 46 normal control subjects. No group differences were found in ability to estimate time intervals. In Study 3, 13 patients with panic disorder and 15 with generalized anxiety disorder showed better heart rate perception than 16 depressed patients.

[Decision-making regarding the acute scrotum]. / Entscheidungshilfe für das akute Skrotum.

An account is given of results obtained from aggressive decisions taken to cope with acute scrotal pain. Thirteen in 121 patients received surgical treatment, although this would have been avoidable, since only epididymitis was eventually detected. That rate, however, had to be accepted due to inadequate reliability of the diagnostic methods so far available, even more so, when the following results are considered: The organ was saved in 39 cases. Pain was removed from 15 cases with pedunculated hydatid. Ten haematomas resulting from blunt testicular trauma were emptied. The surgical approach may be considered suitable for diagnosis, since complications are not to be expected, with the average time of the operation being limited to 18 minutes. The following guideline, therefore, should be observed in cases of post-traumatic, acute testicular pain: Diagnostic exposure is the optional method in cases of even slightest doubt in epididymitis. A sceptical attitude seems to be appropriate for all age groups, particularly when young patients are involved. Surgical exploration is a no-risk and fast approach and the only dependable method to save the organ.

Electrocortical signs of word categorization in saccade-related brain potentials and visual evoked potentials.

Visual evoked potentials (VEPs) elicited by foveal presentation of words were compared to brain potentials evoked by the same words in a condition where subjects had to make a saccadic eye movement in order to perceive the words (saccade-related brain potentials, SRPs). Subjects had to categorize the words responding with a button press to stimuli belonging to the target (infrequent, P = 0.2) category. The VEP and SRP waveforms showed divergences in the early (up to 250 ms) components, but a marked similarity between the late components. Principal Component Analysis also revealed the same relationship between the two types of brain responses. Peak latency of the late SRP components measured from saccade offset showed an apparent processing advantage over the corresponding late components of VEPs. The N3 component, indexing semantic processing of visual patterns, peaked between 310 and 375 ms in the SRPs, while in the VEPs it appeared between 410 and 470 ms. The P4 component, associated with final stimulus evaluation, showed a similar latency benefit in favour of SRPs (420-500 ms vs 530-590 ms in VEPs). The mean reaction time was 74 ms shorter in the eye movement condition (measured from saccade offset) than in the VEP condition (703 vs 777 ms). The question of what kind of processes may contribute to the differences in mean RTs and to the latencies of the late components between the two conditions are discussed. We suggest that the late components (P3, N3 and P4) of the VEP and the SRP, respectively, index identical brain processes.

Saccade-related brain potentials in semantic categorization tasks.

Saccade-related brain potentials (SRPs) were recorded in word categorization tasks in which subjects had to perform a saccade in order to perceive the stimulus. For all three conditions representing different degrees of complexity of semantic categorization, the stimuli belonged to one of two categories which appeared with the respective probabilities of either 0.20 or 0.80. The late positivity (P4) of the SRPs to infrequent stimuli appeared systematically later as the complexity of stimulus evaluation increased: The easiest categorization was accompanied by a P4 at 400 msec, in the more complex condition it peaked at 600 msec, and in the most difficult semantic categorization the P4 peaked even later, at 680 msec. This shift in peak latency with increasing complexity of categorization is in agreement with the results for traditional ERPs (e.g. Kutas and Donchin, 1978). The possible overlap of the late components was investigated by applying Principal Component-Varimax Analysis to the SRPs.

Late components of lambda responses in cognitive tasks.

The effects of stimulus probability were investigated on the late components of saccade-related brain potentials (lambda responses) in two paradigms, 'counting' and 'guessing.' Subjects performed saccadic eye movements from a middle light to the target area where one of three kinds of target light stimuli appeared in a randomized sequence, each with a different probability (0.17, 0.33, and 0.50). Brain activity was recorded from six scalp areas. In the counting task subjects were instructed to count the prespecified low-probability stimuli. In the guessing experiment they had to make a guess before each trial as to which kind of target stimulus would appear. In both experiments the late positive components showed significantly greater amplitude in the lambda responses associated with infrequent stimuli than in those elicited by frequent stimuli. Principal component-Varimax analysis of the lambda responses revealed factors corresponding to the P300 and the slow wave components of traditional evoked potential studies.

Late components of saccade-related brain potentials in guessing tasks.

The late positive components of lambda responses were studied in a guessing task modified in such a way that subjects had to perform a saccadic eye movement in order to perceive task-relevant information. Responses from 6 scalp areas were investigated in 9 subjects and in 2 conditions: control and guessing. In both conditions subjects performed two consecutive saccades in a given trial: the first to the middle light, the second to the target area. In the control condition the subjects knew beforehand what the 'target' would be. In the guessing condition they had to make a guess before each trial as to which of the three target stimuli would appear. The target stimuli occurred with unequal probability and were presented in a randomized sequence. Unlike the control condition, the guessing task led to the appearance of a late positive component in the lambda response. Similar to traditional ERP findings, this late positivity showed an amplitude maximum at the parietal area and a peak latency at 375 msec from saccade onset. Furthermore, Principal Component-Varimax Analysis (PCVA) of the lambda responses revealed a first factor giving the strongest loading in the latency range of the P300, and a second factor which was identified as the slow wave. These factors are quite similar to the factors found in the PCVA of ERPs. Our results suggest that the late components of lambda responses reflect the effects of information processing in cognitive tasks similarly to the way the late positive components of ERPs do.