Size matters: observations regarding the sonographic double contour sign in different joint sizes in acute gouty arthritis.

OBJECTIVE: In distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonography including the detection of the double contour sign (DCS) and hypervascularization using power Doppler ultrasound (PDUS) is an important step in the diagnostic process. But are these sonographic features equally reliable in every accessible joint under real-life conditions? METHODS: We retrospectively analyzed 362 patients with acute arthritis and evaluated the DCS and the degree of PDUS hypervascularization in patients with gout and in those with arthritis other than urate arthritis (non-UA). We classified all joints into the groups small, medium, and large. Sensitivities, specificities, positive and negative predictive values (PPV/NPV), and a binary regression model were calculated. We also evaluated the influence of serum uric acid levels (SUA) on the presence of a DCS in each joint category. RESULTS: Sensitivity of the DCS in gout was 72.5% in the entire cohort, 66.0% in large, 78.8% in medium, and 72.3% in small joints. In wrist joints the DCS sensitivity maxed at 83.3%, with a specificity of 81.8%. The lowest rates of DCS sensitivity were found in gout patients with elbow joint involvement (42.9%). In all joints except metatarsophalangeal joint 1 (MTP-1), the incidence of a DCS increased by the increment of SUA levels above 7.5 mg/dl (p < 0.001). PDUS signals were most commonly found in medium and small joints and were only scarce in large joints, independent of the underlying diagnosis. CONCLUSIONS: In our study we detected different rates of accuracy regarding DCS and PDUS in patients with acute arthritis. The best results were seen in medium-size joints, especially wrists.

Duplex sonography of the mesenteric vessels--a critical evaluation of inter-observer variability.

INTRODUCTION: The number of publications concerning mesenteric Doppler sonography (mesDS) is immense and does not correlate with the frequency of its use in clinical practice. This is astonishing since it provides real time blood flow (perfusion) information without side effects. Despite uncontrollable parameters like the technical limitations in some situations the optimization of (possibly) controllable parameters like standardization, production of normal values and reduction of the investigator variability by evaluating stable parameters could change the situation. PATIENTS AND METHODS: 10 investigators experienced in abdominal sonography ("DEGUM-Seminarleiter") performed mesenteric Doppler sonography in 5 healthy subjects with 5 different machines. RESULTS: The portal vein at the confluence and the common hepatic artery provide a significant portion of investigations with intromission angles of more than 60°. Values of diameter, resistance index and pulsatility index of the celiac trunc could be obtained with inter-observer variability values below 25 %. The proper and the common hepatic artery show no differences in inter-observer variability values, whereas the intrahepatic measure point of the portal vein showed a higher reproducibility. DISCUSSION: We define frame conditions for future mesenteric Doppler studies: the portal vein should be investigated at the intrahepatic measure point. Pathophysiological studies should refrain from velocity parameters except in the case of larger vessels running in a straight course towards the probe.

Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project.

OBJECTIVE: To introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice. METHODS: The ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0-3) by gray-scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0-27 for GS synovitis, 0-39 for PD synovitis, 0-7 for GS tenosynovitis, 0-21 for PD tenosynovitis, and 0-14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease-modifying antirheumatic drug (DMARD) and/or tumor necrosis factor alpha (TNFalpha) inhibitor therapy 3 and 6 months later. C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed. RESULTS: One hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNFalpha inhibitors (41%), or TNFalpha inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (Delta = 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (-32%) and 2.0 (-39%), respectively. CONCLUSION: The German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course.

OBJECTIVE: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". METHODS: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. RESULTS: Taking an agreement in US examination of 10 out of 14 experts into account, the overall kappa for all examined joints was 0.76. Calculations for each joint region showed high kappa values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). kappa Values for bone lesions, bursitis, and tendon tears were high (kappa = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). CONCLUSION: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

[Imaging techniques in rheumatology: sonography in rheumatoid arthritis]. / Bildgebende Verfahren in der Rheumatologie: Sonographie bei rheumatoider Arthritis.

Musculoskeletal ultrasonography has become an important diagnostic tool in rheumatoid arthritis. In Germany it is part of the rheumatology training, and many ultrasound courses provide further education. Only in the last five years the international importance of ultrasound in rheumatology has increased dramatically. Sonography can be performed as a bedside procedure and as an extension of the clinical investigation. It is easily tolerated by the patients, and it can be repeated any time. Sonography can have a great impact on therapeutic decisions. A > or = 5 MHz linear transducer is needed. Most transducers that are used for musculoskeletal ultrasound have about 7.5 MHz. Modern transducers with higher frequencies (>7.5 MHz) and high resolution improve the diagnostic value of the investigation. Sonography is superior to plain radiography to detect erosions as far as the region is accessible by ultrasound. It is more sensitive than the clinical investigation for the detection of synovitis, tenosynovitis, tendinitis, and bursitis as well as for the differentiation of these lesions. Color Doppler sonography aids in evaluating the activity of inflammation and in differentiating intraarticular structures. Carpal- and ulnar neuropathy occur secondary to rheumatoid arthritis and may lead to characteristic nerve swelling. Ultrasound-guided injections into joints and tendon sheets can be performed.

[Technique and diagnostic value of musculoskeletal ultrasonography in rheumatology. Part 6: ultrasonography of the wrist/hand]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik -- Teil 6: Sonographie der Hand- und Fingergelenke.

Sonography of the hands is especially helpful in the diagnosis of early arthritis. Sonography allows for a very sensitive detection of small joint-effusion, tenosynovitis and small erosive bone lesions earlier than conventional radiography. Musculoskeletal sonography is also helpful in morphological analysis of changes of the median nerve in patients with carpal tunnel syndrome. The following standard scans are suggested for the sonographic evaluation of the wrist: 1. dorsal longitudinal scan along the radio-carpal joint, 2) along the ulno-carpal joint, and 3) dorsal transverse scan along the wrist to detect joint fluid collection, synovitis, tenosynovitis, ganglia, irregularities of the bone surface in osteoarthritis, and erosions due to inflammatory disease, 4) volar longitudinal scan along the radio-carpal joint, and 5) along the ulno-carpal joint, and 6) volar transverse scan along the wrist to diagnose the same objective as the above mentioned scans and to evaluate the median nerve in cases of carpal tunnel syndrome. Optional scans are the following: 7) ulnar longitudinal 8) transverse scan along the ulnar joint space and the extensor carpi ulnaris muscle to detect tenosynovitis and caput ulnae syndrome, 9) radial longitudinal, and 10). transverse scan along the joint space to diagnose synovitis and tenosynovitis. The following standard scans are suggested for the sonographic evaluation of the fingers: 1) volar longitudinal, 2) volar transverse scan in extension along the finger joints to detect effusion and synovial proliferation, tenosynovitis, irregularities of the bone surface (osteophytes, erosions), 3) dorsal longitudinal scans in extension and flexion >70 degrees along the CMC I, MCP, PIP and DIP joints to evaluate effusion and synovial proliferation, tenosynovitis or tendinitis, irregularities of the bone surface (osteophytes, erosions), and 4) dorsal transverse scans along the finger joints to evaluate these structures in an additional dimension. Optional 5) scans include the following: medial longitudinal scan along the MCP I, II, PIP and DIP joints, and 6) lateral longitudinal scan along the MCP V, PIP and DIP joints to evaluate the erosive bone process and joint instability. A linear transducer with a frequency of between 7.5 and 12 MHz is recommendable. The anterior distance between the bone and the joint-capsule of the wrist is > or = 3 mm in probable and > or = 4 mm in definite synovitis or effusions. Synovitis or effusions are probable if the difference between right and left wrist is > or = 1 mm, and they are definite if the difference is > or = 2 mm. A carpal tunnel syndrome is probable with a cross-sectional area of the median nerve of > or = 12 mm(2).

[Technical aspects and value of arthrosonography in rheumatologic diagnosis. 4: Ultrasound of the elbow]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik. Teil 4: Sonographie des Ellenbogens.

Musculoskeletal ultrasonography is an important imaging technique in the diagnosis of rheumatic diseases especially for early manifestation. It allows sensitive detection of small joint fluid collections as well as differentiation of soft tissue lesions and bone lesions. The following standard scans are suggested for sonographic evaluation of the elbow: 1) anterior humeroradial longitudinal scan, 2) anterior humeroulnar longitudinal scan to detect effusions, synovial proliferation, loose joint bodies, bone lesions (osteoarthritis/arthritis), 3) anterior transverse scan over the trochlea to evaluate these structures in an additional dimension, 4) posterior longitudinal scan and 5) posterior transverse scan of the olecranon fossa with flexed/extended elbow to evaluate the same objectives as the above mentioned scans and additionally to detect olecranon bursitis, and optional 6) distal dorsal longitudinal scan to differentiate soft tissue lesions such as rheumatoid nodules or gout tophi, 7) anterior transverse scan over the radius head to evaluate lesions of the radius head, tendopathy, calcinosis, 8) lateral humeroradial longitudinal scan to evaluate epicondylitis, 9) medial humeroulnar longitudinal scan to evaluate calcinosis, epicondylitis, signs of compression of the ulnar nerve. A linear transducer with a frequency of about 5-7.5 MHz is recommendable. The anterior distance between trochlea and the capitulum of the humerus between the bone and the joint-capsule of the elbow is > or = 2 mm in probable and > or = 3 mm in definite synovitis or effusions. Synovitis or effusions are probable if the difference between the right and left elbow is 1 mm, and they are definite if the difference is > or = 2 mm.

[Technique and diagnostic value of musculoskelatal ultrasonography in rheumatology. Part 5: Ultrasonography of the shoulder]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik -Teil 5: Sonographie des Schultergürtels.

Shoulder-related symptoms are very common in rheumatic diseases. For the evaluation of the diagnosis as well as for therapy and prognosis, an anatomic assignment is essential. Clinical investigations alone are often not capable to do this. Ultrasonography is a method to delineate bony surfaces as well as the soft tissues around the shoulder joints statically and even dynamically. For the purpose of rheumatic diseases, ultrasound standard scans help to detect the lesions at the biceps tendon, the bursae, the rotator cuff, the humeral head as well as in the acromial and sternoclavicular joints. Considering the limitations of the method (obesity, frozen shoulder, no findings under bony structures) and knowing the pitfalls and errors of the method, ultrasonography is a reliable, quick and low cost method for the diagnosis of rheumatic shoulder joint pathology. Compared to computer tomography and magnetic resonance imaging, ultrasonography should be used as a screening method. The following standard scans are suggested for sonographic evaluation of the shoulder: 1) anterior transverse scan and 2) anterior longitudinal scan at the bicipal groove to detect synovitis and tenosynovitis, 3) anterior transverse scan at the coracoacromiale window in the neutral position, 4) at maximal external rotation and 5) at maximal internal rotation to evaluate the rotator cuff, bursitis, synovitis and erosions, 6) anterior longitudinal scan at 90 degrees to the coracoacomiale window at maximal internal rotation to describe these findings in an additional dimension, 7) anterior-lateral longitudinal scan at the anterior lateral acromion to tuberculum majus to evaluate the distal part of the supraspinatus muscle, 8) posterior transverse scan at the fossa infraspinata lateral under the spina scapulae, 9) axillary longitudinal scan to evaluate synovitis, synovial proliferation, erosions at the humeral head, lesions at the glenoidale labrum, 10) anterior transverse scan at the acromioclavicular joint and 11) anterior oblique scan at the sternoclavicular joint to detect synovitis, synovial proliferation, erosion, osteophytes.

[Technique and value of arthrosonography in rheumatologic diagnosis--3: Ultrasound diagnosis of the ankle joint, foot and toes]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik--Teil 3: Sonographie der Sprunggelenke, des Fusses und der Zehen.

The clinical investigation of ankles, feet, and toes is frequently equivocal in rheumatology. Sonography can distinguish between underlying pathologies. We suggest following standard scans: 1) anterior longitudinal scan to diagnose effusions in the ankle and talonavicular joints, to display erosive and osteoarthrotic pathologies, and to diagnose tenosynovitis of the extensor tendons; 2) anterior transverse scan to document the findings in an additional dimension; 3) lateral transverse scan and 4) lateral longitudinal scan to diagnose tenosynovitis of the peroneus tendons; 5) medial transverse scan and 6) medial longitudinal scan to diagnose tenosynovitis of the flexor tendons; 7) posterior longitudinal scan and 8) posterior transverse scan to evaluate the Achilles tendon, the retrocalcaneal bursa, and the posterior recess of the ankle joint. Additionally we suggest optional scans: 9) plantar longitudinal scan for the plantar fascia and the plantar calcaneal surface; 10) distal anterior longitudinal scan to evaluate the midtalar joints; 11) distal anterior longitudinal scan to evaluate the toes; and 12) plantar, distal transverse scan to evaluate the flexor tendons of the toes. Additionally, the correlating longitudinal and transverse scans can be used to confirm the findings. The frequency of the transducer should be about 7.5 MHz for ankles and the peroneus, flexor, and extensor tendons. Ten to over 20 MHz are possible for more superficially located structures. Using modern equipment with higher resolution a hypoechoic border may be normal up to 3 mm in the ankle joints, the MTP joints, and around the peroneus tendons, and up to 4 mm around the tibialis posterior tendons.

[Technique and value of arthrosonography in rheumatologic diagnosis. 2: Ultrasound diagnosis of the hip area]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik. Teil 2: Sonographie der Hüftregion.

The clinical investigation of the hips in patients with rheumatic diseases is often equivocal. Thus, ultrasonography of this region is very relevant for rheumatologists. We suggest following standard scans: 1) anterior longitudinal scan to detect synovitis of the hip joint, iliopectineal bursitis, irregularities of the bone surface in osteoarthritis, Perthes' disease, and erosions due to inflammatory disease, 2) anterior transverse scan to evaluate these structures in an additional dimension, 3) lateral longitudinal scan of the hip joint with the same objective as the above mentioned scans; 4) lateral longitudinal scan, and 5) lateral transverse scan of the greater trochanter to diagnose trochanteric bursitis and bone irregularities due to enthesiopathy, and 6) dorsal oblique scan (optional) to diagnose hip joint effusions and pannus that localize in the dorsal region. Rotation of the joint is necessary to detect small effusions. The transducers should have a medium frequency of 5 to 7.5 MHz. In obese or muscular patients, 3.5 MHz transducers may be necessary to increase penetration. The anterior distance between the bone and the joint capsule of the hip joint is > or = 7 mm in probable and > or = 8 mm in definite synovitis or effusions. Synovitis or effusions are probable if the difference between right and left hip is > or = 2 mm, and they are definite if the difference is > or = 3 mm.

[Ultrasound diagnosis in rheumatoid omarthritis]. / Sonographie bei rheumatischer Omarthritis.

There are specific and unspecific signs of omarthritis. The more specific the signs seen together in connection with laboratory and clinical findings are, the more certain the result becomes. A complete scanning is necessary including axillary as well as static and dynamic examinations.

[Ultrasound diagnosis of hand and finger joints. Changes in arthritis]. / Sonographie der Hand- und Fingergelenke. Veränderungen bei Arthritis.

Arthritis of the hand and finger joints is seen with unspecific and specific signs, as known from the hip and knee joints. The examination has to be done with special applicators (small sized with 7-13 MHz). Especially signs such as erosions and surrounding synovitis ensure the diagnosis of rheumatoid arthritis.

[Coxarthritis]. / Koxarthritis.

Coxarthritis is seen with specific and unspecific signs. The more specific signs are available in connection with clinical and laboratory findings, all the more certain is the result. Static and dynamic examinations are as necessary as a complete scanning of the dorsal side of the femoral head.

[Ultrasound of the knee joint in gonarthritis]. / Sonographie des Kniegelenks bei Gonarthritis.

Ultrasound examination of the knee joint to detect early signs of inflammation is a useful diagnostic tool. The more specific the signs seen in connection with clinical and laboratory findings are, the more certain the diagnosis becomes. Static and dynamic examinations are necessary.

[Ultrasonography in inflammatory rheumatic diseases]. / Sonographie bei entzündlich-rheumatischen Erkrankungen.

In addition to clinical and laboratory findings, ultrasound is a very useful imaging procedure for the diagnosis of all rheumatic diseases. This method is able to monitor their development and dynamics. All joints that can be reached by the ultrasound beam are examined (from large ones such as the shoulder and knee to small ones such as fingers and toes) with various techniques and different frequencies.

[Technique and value of arthrosonography in rheumatologic diagnosis. 1: Ultrasound diagnosis of the knee joint]. / Technik und Stellenwert der Arthrosonographie in der rheumatologischen Diagnostik. Teil 1: Sonographie des Kniegelenks.

Within the last few years, ultrasonography (US) of joints has attained a firm position for the diagnosis of joint diseases. Degenerative as well as inflammatory changes can be recognized using this method. With new, higher resolution techniques even bone surfaces and tendon textures can be visualized in greater detail. The advantages of sonography are general availability and low costs. When used properly, as a non-invasive procedure US has no detrimental effects on patients. The disadvantages of this technique result from its physical limitations, such as high reflection of US on bone and the negative correlation between resolution and penetration which makes US imaging difficult in deeper regions. The current technical development of probes and imaging processing, however, promises better deep structure imaging in the future. The quality of ultrasound examination always depends on the technical equipment, as well as on the patients' individual tissue constitution and the experience of the physician. It is possible to avoid misinterpretation and to increase the diagnostic value of US by using a standardized technique and professional knowledge of the specific aspects of the method. The significance of qualified education and sufficient training of sonographers is to be stressed. The aim of this article is to deliver a basic contribution to the standardization and quality assurance of joint US and to indicate the value of this method. In addition to the overview the authors propose guidelines for performance and interpretation of joint US. Due to the major significance of the knee joint in rheumatology it was decided to begin the work in this area.

Novel amplification unit at chromosome 3q25-q27 in human prostate cancer.

BACKGROUND: In prostate carcinoma, amplification of the genes c-MYC, Her2/NEU, and the androgen receptor gene has been documented, with gene amplification being related to progressive tumor growth. Recently, using comparative genomic hybridization (CGH), we provided evidence for DNA copy number gains at chromosome 3q25-q26 in prostate cancer [Sattler et al.: Prostate 39:79-86, 1999]. METHODS: In this study, additional prostatic tumors were evaluated by CGH to determine the frequency of DNA overrepresentation at 3q. Comparative PCR and Southern blot analyses were applied to determine whether known genes are involved in DNA copy number gains. RESULTS: By CGH, DNA copy number gains, all of which involved chromosome region 3q25-q26, were disclosed in 50% of the prostate tumors analyzed. There was no evidence for high-level amplification. The analysis of 12 genes from 3q25-q27 by comparative PCR revealed amplification in 6 (35.3%) of 17 tumors tested. Amplification was detected for the genes IL12A, MDS1, SLC2A2, and SOX2, with coamplification of three genes in two tumors. IL12A was amplified as single gene in three tumors and in a subline of the DU145 cell line, SLC2A2 in one tumor. CONCLUSIONS: Our studies revealed a novel amplification unit at 3q25-q27 in prostate carcinoma, with the genes IL12A, MDS1, SLC2A2, and SOX2 being located within the amplification unit. A common region of amplification was evident spanning the IL12A gene locus at 3q25-q26.2. Possibly, IL12A indicates an adjacent, till now unidentified gene which is important in the development of prostate cancer.

Expression of the human telomerase reverse transcriptase is not related to telomerase activity in normal and malignant renal tissue.

In this study, the association between telomerase activity and the expression of the human telomerase subunits human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in paired neoplastic and normal renal tissue samples was investigated. Reverse transcription (RT)-PCR on 20 tumor nephrectomy samples revealed that hTR was constitutively expressed both in cancer and normal tissue samples, independent of the telomerase activity status. Remarkably, using in situ hybridization, the expression levels of hTR were found to be markedly higher in the normal tissue than those in the tumors. Expression of hTERT mRNA by RT-PCR was observed in 90% of the cancer samples and, notably, also in 75% of the corresponding normal renal tissue samples. Because all of the normal tissue samples and some of the tumor samples were shown to be telomerase negative, our findings suggest that hTERT mRNA expression is not sufficient for telomerase enzyme activation. Furthermore, semiquantitative RT-PCR revealed equal or even higher hTERT mRNA expression levels in the telomerase-negative normal samples than in the corresponding cancer samples with telomerase activity, contradicting the assumption that a certain threshold level of hTERT mRNA is required for telomerase activation at least in renal tissue. It seems more likely, that other mechanisms, such as posttranscriptional modification of hTERT or inactivation of telomerase inhibitors, are involved in the acquisition of enzyme activity.

Neurophysiologic tests during antidepressive treatment - an exploratory study.

This is a non-randomized exploratory study showing the sensitivity of neurophysiological parameters for autonomic side-effects during the application of antidepressant drugs. Inpatients on tricyclic antidepressants (TCA: amitriptyline or doxepine), inpatients on serotonine-reuptake inhibitors (SSRI: fluvoxamine or paroxetin) and a control group of healthy volunteers underwent neurophysiological examination. The treatment group was investigated after at least 7 days of continuous treatment with the final dose. Adjustment of the autonomic nervous system was studied, first, by measuring latency and amplitude of the sympathetic skin response (SSR), elicited by electric stimuli and by deep inspiration, and second, by analysis of the heart rate variation (HRV) during rest and inspiration. Relevant affections of the peripheral parts of the reflex arc under discussion were excluded by taking the nerve conduction velocity (NCV) and F-wave referring to cervical segment C7. In total, 48 individuals were examined. The TCA group showed delayed latencies and smaller amplitudes of the SSR in comparison with the controls. In the SSRI group, these parameters did not differ significantly from those of the controls. Analysis of HRV put further emphasis on the impaired adjustment of the autonomic nervous system in the TCA group. To sum up, our test battery indicated a specific vegetative alteration due to TCA.