[Current aspects of tinnitus and depression]. / Aktuelle Aspekte zu Tinnitus und Depression.

Health authorities underestimate the negative influence of emotional factors such as depression, anxiety disorders, or somatoform disorders in the development of tinnitus and their contribution to a poor prognosis. This can lead to underestimation of the impairment suffered by tinnitus patients and, consequently, a possibly incorrect treatment approach or belated initiation of therapy. Mental disorders play a large role in the S3AWMF "Tinnitus" guidelines. Thus, the somatic and psychiatric approaches for treatment of chronic tinnitus patients are combined. Starting with taking chronic tinnitus patients' case history, special attention should be paid to comorbid mental disorders.

Pain perception during debridement of hypersensitive teeth elicited by two ultrasonic scalers.

OBJECTIVES: The ultrasonic NO PAIN technology (Electro Medical Systems, Nyon, CH) promises minimal pain during debridement due to linear oscillating action combined with a sinusoidal power output and feedback control. The aim of the present study was to measure pain perception on a visual analogue scale (VAS) during supportive periodontal therapy including debridement of hypersensitive teeth. Two ultrasonic scalers were used, one with and one without NO PAIN technology. MATERIAL AND METHODS: In a randomized-controlled clinical study with split-mouth design, 100 hypersensitive teeth matched for air blast hypersensitivity were either treated with the ultrasonic device Piezon Master 700 or the Mini Piezon (both EMS, Nyon, CH). Pain perception during debridement was assessed by a VAS (range 0-10). RESULTS: The average VAS for the test device Piezon Master 700 with NO PAIN technology was 3.16 ± 2.10, and for the control device Mini Piezon without NO PAIN technology 3.40 ± 2.59 (p = 0.490). Placing an arbitrary threshold at the VAS score of 3 for significant pain experience, 60 % of the subjects experienced no significant pain with either instrument. CONCLUSION: No statistically significant difference in perceived pain between the instruments used was found. CLINICAL RELEVANCE: Both ultrasonic devices showed very small pain intensities during debridement of highly hypersensitive teeth and can therefore be recommended for supportive periodontal therapy.

Long-term Clinical Outcome and Functional Status After Arterial Reconstruction in Upper Extremity Injury.

OBJECTIVE/BACKGROUND: To analyse long term outcome, including functional status and prognostic factors, in patients who have undergone arterial repair of civilian upper limb injury. Retrospective data analysis of prospectively collected data was performed. METHODS: This was a retrospective data analysis of prospectively collected data. Records of all patients who had undergone repair of traumatic arterial lesions in the upper limb between 1989 and 2010 were reviewed, and clinical follow up was performed. End points were: long term patency, measured by color Doppler ultrasound; vascular re-intervention; limb salvage rate; and long term functional status using the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire. The DASH questionnaire is an instrument used to identify a patient's disabilities, in which everyday activities are assessed by 30 questions. The DASH answers are summarized and, using a conversion formula, lead to a score between 0 (full recovery) and 100 (severe disability). The DASH questionnaire was sent to all German-speaking individuals for data supplementation after completion of a clinical follow up study. RESULTS: A total of 117 arterial repairs were performed in 108 patients (87 men, median age 35.7 years). Blunt trauma was the predominant cause of injury (n = 96; 82%). Accompanying nerve lesions (n = 39; 36%) and/or orthopedic injuries (n = 65; 60%) were present in 84 patients (78%). After a median follow up time of 5.3 years (range 0.5-19.7 years), 65 patients (60%) were re-investigated: long-term patency was 97%. The DASH questionnaire was answered by 57 patients (53%). Functional impairment was frequently seen, and determined by neurological injury (including neurological lesions, median DASH score was 40.3 [range 3.5-69.8] vs. 0.8 [range 0-5.8] without; p < .001) and ischemia at time of injury (median DASH score with ischemia 4.2 [range 0-16.9] vs. 0.0 [0-1.7] without; p < .04). CONCLUSION: Favorable long term patency rates after arterial repair in upper extremity injuries can be achieved. Long term functional impairment is a significant problem and determined by associated neurological injury, as well as ischemia at time of injury.

[Tinnitus and psychiatric comorbidities]. / Psychische Komorbidität bei Tinnitus.

Tinnitus is an auditory phantom phenomenon characterized by the sensation of sounds without objectively identifiable sound sources. To date, its causes are not well understood. The perceived severity of tinnitus correlates more closely to psychological and general health factors than to audiometric parameters. Together with limbic structures in the ventral striatum, the prefrontal cortex forms an internal "noise cancelling system", which normally helps to block out unpleasant sounds, including the tinnitus signal. If this pathway is compromised, chronic tinnitus results. Patients with chronic tinnitus show increased functional connectivity in corticolimbic pathways. Psychiatric comorbidities are common in patients who seek help for tinnitus or hyperacusis. Clinicians need valid screening tools in order to identify patients with psychiatric disorders and to tailor treatment in a multidisciplinary setting.

[On the interdisciplinary S3 guidelines for the treatment of chronic idiopathic tinnitus]. / Zur interdisziplinären S3-Leitlinie für die Therapie des chronisch-idiopathischen Tinnitus.

INTRODUCTION: Tinnitus is a frequent symptom, which, particularly in combination with comorbidities, can result in a severe disease-related burden. Chronic idiopathic tinnitus (CIT) is the most frequent type of tinnitus. A considerable number of treatment strategies are used to treat CIT-for many of which there is no evidence of efficacy. In order to enable scientific evidence-based treatment of CIT, German interdisciplinary S3 guidelines have recently been constructed for the first time. Here we present a short form of these S3 guidelines. MATERIALS AND METHODS: The guidelines were constructed based on a meta-analysis of the treatment of chronic tinnitus performed by the authors. Additionally, a systematic literature search was performed in the PubMed and Cochrane Library databases. Furthermore, a systematic search for international guidelines was performed in Google, as well as in the Guidelines International Network and National Guideline Clearinghouse (USA) database. Evidence was classified according to the Oxford Centre for Evidence-Based Medicine system. RESULTS: According to the guidelines, alongside counselling, manualized structured tinnitus-specific cognitive behavioral therapy (tCBT) with a validated treatment manual is available as evidence-based therapy. In addition, the guidelines recommend concurrent treatment of comorbidities, including drug-based treatment, where appropriate. Particularly important is treatment of anxiety and depression. Where a psychic or psychiatric comorbidity is suspected, further diagnosis and treatment should be performed by an appropriately qualified specialist (psychiatrist, neurologist, psychosomatic medicine consultant) or psychological psychotherapist. In cases accompanied by deafness or hearing loss bordering on deafness, cochlear implants may be indicated. CONCLUSION: No recommendations can be made for drug-based treatment of CIT, audiotherapy, transcranial magnetic or electrical stimulation, specific forms of acoustic stimulation or music therapy; or such recommendations must remain open due to the lack of available evidence. Polypragmatic tinnitus treatment with therapeutic strategies for which there is no evidence of efficacy from controlled studies is to be refused.

Analysis of mental disorders in tinnitus patients performed with Composite International Diagnostic Interview.

PURPOSE: Known association between tinnitus and psychological distress prompted us to examine patients with chronic tinnitus by using the Composite International Diagnostic Interview (CIDI), which is a standardized and reliable method used for the diagnosis of mental disorders. METHODS: One hundred patients with chronic tinnitus admitted to the Tinnitus Center, Charité-Universitätsmedizin Berlin, were included in this study. Data were collected between February 2008 and February 2009. Besides CIDI, the Tinnitus Questionnaire according to Goebel and Hiller, the Hospital Anxiety Depression Scale, and the General Anxiety Disorder-7 were used. RESULTS: Using CIDI, we have identified one or more mental disorders in 46 tinnitus patients. In that group, we found persistent affective disorders (37 %), anxiety disorders (32 %), and somatoform disorders (27 %). Those patients who had affective or anxiety disorders were more distressed by tinnitus and were more anxious and more depressed than tinnitus patients without mental disorders. Psychological impairment positively correlated with tinnitus distress: Patients with decompensated tinnitus had significantly more affective and anxiety disorders than patients with compensated tinnitus. CONCLUSIONS: In the present study, we have detected a high rate (almost half of the cases) of psychological disorders occurring in patients with chronic tinnitus. The patients diagnosed with psychological disorders were predominantly affected by affective and anxiety disorders. Psychological disorders were associated with severity of tinnitus distress. Our findings imply a need for routine comprehensive screening of mental disorders in patients with chronic tinnitus.

Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.

BACKGROUND: The role of CHAC1 (cation transport regulator-like protein 1), a recently identified component of the unfolded protein response (UPR) pathway, in gynaecological cancers has not yet been characterised. Now, this work illustrates CHAC1 mRNA expression and associated clinical outcome in breast and ovarian cancer. METHODS: The prognostic value of CHAC1 and its two transcript variants was investigated in 116 breast and 133 ovarian tissues using quantitative real-time reverse-transcriptase PCR. Subsequently, we conducted functional studies using short-interfering RNA-mediated knockdown and plasmid-mediated overexpression of CHAC1 in breast and ovarian cancer cells. RESULTS: Poorly differentiated tumours exhibited higher CHAC1 mRNA expression (breast cancer: P=0.004; ovarian cancer: P=0.024). Hormone receptor-negative breast tumours and advanced-staged ovarian cancers demonstrated elevated CHAC1 mRNA expression levels (P<0.001 and P=0.026, respectively). The multivariate survival analysis showed a prognostic value of both transcript variants in breast cancer (transcript variant 1: RR(death) 6.7 (2.4-18.9); P<0.001), RR(relapse) 6.7 (2.1-21.3); P=0.001); (transcript variant 2: RR(death) 4.9 (2.0-12.4); P<0.001), RR(relapse) 8.0 (2.4-26.8); P<0.001). Ovarian cancer patients aged younger than 62.6 years with high CHAC1 mRNA expression showed poorer relapse-free- and overall-survival (P=0.030 and P=0.012, respectively). In functional studies CHAC1 knockdown suppressed cell migration, whereas ectopic overexpression opposed these effects. CONCLUSION: High CHAC1 mRNA expression could be an independent indicator for elevated risk of cancer recurrence in breast and ovarian cancer.

Influence of use of a vascular closure device on incidence and surgical management of access site complications after percutaneous interventions.

AIM: The study aimed to evaluate vascular access site complications (ASCs) after percutaneous interventions (PIs) in our institution for changes in annual incidence and surgical management after increased usage of a vascular closure device (VCD; in all cases: Angioseal™). MATERIAL AND METHODS: All patients who underwent repair of arterial pseudo-aneurysms or access site stenosis/occlusion leading to leg ischaemia (LI) or new-onset disabling claudication (CI) after PIs between 2001 and 2008 were included. Annual rates of procedures and methods of repair of ASC were evaluated. RESULTS: After a total of 58 453 PIs, 352 patients (0.6%) were operated on for: pseudo-aneurysms (n = 300; 0.51%); and local stenosis/occlusion leading to LI/CI (n = 52; 0.09%). Numbers increased significantly with more widespread VCD use: group A (2001-2004: 2860 VCDs; 28 284 PIs; 10.1%): n = 132 (0.47%); and group B (2005-2008: 11,660 VCDs; 30,169 PIs; 38.6%): n = 220 (0.73%) (p < 0.001). In contrast to similar rates of pseudo-aneurysms (group A: n = 124; 0.44%; group B: n = 176; 0.58%; not significant), a significant increase of operations for local stenoses/occlusions was seen with widespread VCD use: n = 8 versus n = 44 (p < 0.001). CONCLUSIONS: In the era of VCDs, complications are rare. However, use of these devices is not without complications, and may require complex reconstructions.

[Tinnitus and psychological comorbidities]. / Tinnitus und psychische Komorbiditäten.

Comorbidity is the presence of one or more disorders in addition to the main disorder. Comorbidities negatively influence the development of the main disease. For patients with tinnitus a comorbidity is an additional component complicating the habituation of ear noise and patients with decompensated tinnitus often have psychological comorbidities, e.g. affective, somatoform or anxiety disorders. At the time of first presentation and also during further follow-up, it is essential to pay particular attention to the presence of potential comorbid mental disorders. This is of special importance for patients with decompensated ear noise (severity grades 3 and 4). For ENT specialists it is important that the mental discomfort of patients must be taken seriously and should be identified through a targeted diagnosis. Effective treatment of the co-symptoms using cognitive behavior therapy (CBT) in conjunction with medication often reduces the severity of tinnitus perception and discomfort.

Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial.

BACKGROUND AND OBJECTIVES: Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. SUBJECTS AND METHODS: We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. RESULTS: Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. CONCLUSION: Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.

Gene methylation data--a new challenge for bioinformaticians?

OBJECTIVES: Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia. For the first time, we reported on the analysis of fecal DNA from patients with CRC to determine the feasibility, sensitivity and specificity of this approach. We want to present basic information about DNA methylation analysis in the context of bioinformatics, the study design and several statistical experiences with gene methylation data. Additionally we outline chances and new research questions in the field of DNA methylation. METHODS: We present current approaches to DNA methylation analysis based on one reference study. Its study design and the statistical analysis is reflected in the context of biomarker development. Finally we outline perspectives and research questions for statisticians and bioinformaticians. RESULTS: Identification of at least three genes as potential DNA methylation-based tumor marker genes (SFRP2, SFRP5, PGR). CONCLUSIONS: DNA methylation analysis is a rising topic in molecular genetics. Gene methylation will push the extension of biobanks to include new types of genetic data. Study design and statistical methods for the detection of methylation biomarkers must be improved. For the purpose of establishing methylation analysis as a new diagnostic/prognostic tool the adaptation of several approaches has become a challenging field of research activity.

Sagittal wrist motion of carpal bones following intraarticular fractures of the distal radius.

Forty patients (mean age, 37 years) with intraarticular C2 and C3 Colles fractures were treated by open reduction, internal fixation and bone grafting. At a mean follow-up of 8 years radiocarpal and midcarpal motion was evaluated, the depth of the articular surface of the distal radius in the sagittal plane was measured and the presence of arthritis was noted. The fractures healed with a mean palmar tilt of 6 degrees , a mean ulnar tilt of 18 degrees and ulna variance within 1 mm of the contralateral side. The depth of the articular surface of the distal radius was 1.3 mm greater than the uninvolved side. Measurement of carpal bone angles relative to the radius in maximum flexion and extension revealed lunate extension of 23 degrees , lunate flexion of 15 degrees , capitate extension of 62 degrees , capitate flexion of 40 degrees . There was a significant correlation between articular surface depth and radiocarpal motion.

[Therapy for static scapholunate instability -- reconstruction of the dorsal part of the scapholunate ligament with a periosteal flap of the iliac crest]. / Therapie der statischen skapholunären Instabilität -- Bandrekonstruktion des dorsalen skapholunären Bandes mit einem Perioststreifen vom vorderen Darmbeinkamm.

Recurrent instability is frequent following capsulodesis, tenodesis, or ligament reconstruction in static scapholunate instability. Therefore a periosteal flap of the iliac crest was designed to reconstruct the dorsal part of the SL ligament, which is known to be the biomechanically strongest portion and also the axis of rotation between the scaphoid and lunate. Biomechanical testing of ten fresh frozen dorsal SL ligaments and ten periosteal flaps of the iliac crest showed similar properties concerning failure force, failure displacement, failure stress, energy to failure and stiffness. Results of eight specimens in each group were available following successful testing. Failure force of the dorsal SL ligament was 171.8 N (SD 44.2), energy to failure amounted 269.1 N-mm (SD 98.9), failure stress was 10.3 N/mm (2) (SD 1.3), failure displacement 2.9 mm (SD 0.4), and stiffness 77.2 N/mm (SD 21.4). Testing of the periosteal flap gave the following values: failure force 144.3 N (SD 38.7), energy to failure 217.9 N-mm (SD 85.0), failure stress 9.9 N/mm (2) (SD 1.7), failure displacement 3.0 mm (SD 0.4) and stiffness 60.5 N/mm (SD 14.7). In addition to these test values, clinical and radiological data of eleven patients were available following reconstruction of the dorsal SL ligament with a periosteal flap of the iliac crest. The interval between trauma and surgery was 15 months, mean follow-up was 29 months. One patient was free of pain, whereas ten mentioned pain during or following strenuous work. Two patients were completely satisfied, nine complained about some restriction during special activities. Active range of motion amounted to 56 degrees extension, 46 degrees flexion, 17 degrees radial abduction, 30 degrees ulnar abduction. Grip strength was 38.5 kg, which was 79 % of the contralateral side. Radiological evaluation demonstrated a correction of the static instability in nine cases. In two patients recurrence of static instability was obvious. The prerequisite for success of the procedure is the easy reduction of the carpals. In cases of a fixed rotatory subluxation of the scaphoid, the technique cannot maintain the reduction.

Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy).

This study characterizes paw reaching, stepping and balance abnormalities in a double lesion rat model of striatonigral degeneration, the core pathology underlying levodopa unresponsive parkinsonism associated with multiple system atrophy. Extensive unilateral nigral or striatal lesions induced by 6-hydroxydopamine or quinolinic acid, respectively, produced a similarly marked contralateral paw reaching deficit without further deterioration following a secondary (complementary) lesion of ipsilateral striatum or substantia nigra. Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions without further deterioration following the secondary striatal lesion. In contrast, initial unilateral striatal quinolinic acid injections induced bilateral stepping deficits that significantly worsened contralaterally following the secondary nigral lesion. Contralateral sidefalling rates were significantly increased following primary nigral and striatal lesions. Secondary nigral but not secondary striatal lesions worsened contralateral sidefalling rates. Histological studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia nigra pars compacta and variable degrees of striatal degeneration depending on the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed significantly larger residual striatal surface areas following the secondary striatal quinolinic acid lesion compared to animals with primary striatal quinolinic acid lesions (P<0.001). These findings are in line with previous experimental studies demonstrating that striatal dopamine depletion confers neuroprotection against subsequent excitotoxic injury. Whether loss of dopaminergic neurons protects against the striatal disease process occurring in multiple system atrophy (Parkinson-type) remains to be elucidated. In summary, this is the first experimental study to investigate spontaneous motor behaviour in a unilateral double lesion rat model. Our observations are consistent with a complex interaction of nigral and striatal lesions producing distinct behavioural and histological changes depending on the lesion sequence. Tests of forelimb akinesia and complex motor behaviour appear to provide a reliable tool that will be helpful for monitoring the effects of interventional strategies such as embryonic neuronal transplantation in the rat model of striatonigral degeneration.

A psychometric study of complaints in chronic tinnitus.

Dimensions of psychological complaints due to chronic and disabling tinnitus were investigated by means of the Tinnitus Questionnaire (TQ), administered to a sample of 138 tinnitus sufferers who had been admitted to a psychosomatic hospital. Factor analysis revealed that tinnitus-related patterns of emotional and cognitive distress, intrusiveness, auditory perceptual difficulties, sleep disturbances, and somatic complaints can be differentiated. Cognitive distortions and inappropriate attitudes towards the tinnitus and it's personal consequences were found to be highly intercorrelated forming a subgroup within a broader and more general distress factor. The stability of the factor solution obtained was examined by systematically varying the number of factors to be extracted. Based on the results of this method, scales are proposed for the questionnaire which can be used in clinical and scientific work to specifically assess major areas of tinnitus-related distress and their degree of severity. Implications for a further evaluation of the instrument are discussed.

Meeting the expectations of chronic tinnitus patients: comparison of a structured group therapy program for tinnitus management with a problem-solving group.

Two different group treatments were evaluated in 144 in-patients suffering from impairment due to chronic tinnitus. A tinnitus management therapy (TMT) was developed using principles of cognitive-behavioral therapy and compared with problem solving group therapy. Self-ratings were used to evaluate the help patients found in dealing with life problems and tinnitus as well as the degree to which they felt they were being properly treated and taken seriously. Patients showed significantly more satisfaction with the TMT group and evaluated the help they found in coping with tinnitus and life problems significantly higher. Thus, in the light of unsatisfactory medical solutions and the poor acceptance of some psychological treatments for tinnitus, TMT appears to be an acceptable and helpful treatment program.

Use of low molecular mass heparin (enoxaparin) in newborn infants: a prospective cohort study of 62 patients.

OBJECTIVE: To detail low molecular mass heparin (enoxaparin) use in the first few months of life. DESIGN: Prospective, consecutive cohort of unselected newborn infants. METHODS: Newborn infants were divided into groups by gestational age, underlying condition, hepatic and renal function, thrombocytopenia, and prothrombin time (PT/INR). Groups were analysed with respect to many aspects of enoxaparin treatment using multivariate methods. RESULTS: Sixty two newborn infants received enoxaparin representing 5.39 treatment years. Thromboembolic events (TEs) occurred predominantly in the lower and upper venous system in the presence of indwelling catheters (69%). Preterm infants required longer than full term infants to achieve an anti-(factor Xa) level in the target range (six versus two days). Preterm infants required higher doses of enoxaparin than full term infants to maintain anti-(factor Xa) levels in the target range (2.1 v 1.7 mg/kg/12 h). Infants with congenital heart disease (CHD) required less enoxaparin than those without CHD to maintain an anti-(factor Xa) level in the target range (1.7 v 2.1 mg/kg/12 h). Impaired renal and liver function influenced the number of dose changes needed (three versus one a month). Complete or partial resolution of TE was accomplished in 59% of newborn infants. Four infants developed major bleeds (1.2% per patient year). Recurrent TE and clot extension occurred in three infants (0.9% per patient year). CONCLUSIONS: Preterm infants are more difficult to treat with enoxaparin than full term infants. Enoxaparin appears to be an alternative to treatment with standard heparin or no treatment.

Reliability of self-rated tinnitus distress and association with psychological symptom patterns.

Psychological complaints were investigated in two samples of 60 and 138 in-patients suffering from chronic tinnitus. We administered the Tinnitus Questionnaire (TQ), a 52-item self-rating scale which differentiates between dimensions of emotional and cognitive distress, intrusiveness, auditory perceptual difficulties, sleep disturbances and somatic complaints. The test-retest reliability was .94 for the TQ global score and between .86 and .93 for subscales. Three independent analyses were conducted to estimate the split-half reliability (internal consistency) which was only slightly lower than the test-retest values for scales with a relatively small number of items. Reliability was sufficient also on the level of single items. Low correlation between the TQ and the Hopkins Symptom Checklist (SCL-90-R) indicate a distinct quality of tinnitus-related and general psychological disturbances.