VGF function in depression and antidepressant efficacy.

Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germ line (Vgf+/-) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wild-type mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.

[Potential of Adaptive Optics for the Diagnostic Evaluation of Hereditary Retinal Diseases]. / Adaptive Optiken ­ Möglichkeiten für die Diagnostik hereditärer Netzhauterkrankungen.

The use of adaptive optics in ophthalmoscopy is a breakthrough technological achievement. With AO ophthalmoscopes, the microscopic retinal structure can be visualised non-invasively and on a cellular level, allowing for cellular scale imaging of the retinal nerve fibre layer, the smallest retinal capillaries, rod and cone photoreceptors, and the retinal pigment epithelium mosaic in the living subject. Regarding the diagnostic evaluation of retinal diseases, the current research focuses on monogenetic retinal diseases, which - when better understood - may allow for conclusions to be drawn about other multifactorial diseases and their underlying mechanisms (model disease). For disease monitoring and current and future pharmacological intervention (e.g. gene therapy), they will help to better establish novel and reliable clinical endpoints. New AO imaging devices have just become commercially available, and the number of retinal pathologies visualised with AO is increasing. Recently, an AO-based microstimulation technique has been introduced, which offers the possibility to directly correlate retinal structure with visual function on a cellular level.

[Switching Therapy from Ranibizumab and/or Bevacizumab to Aflibercept in Neovascular Age-Related Macular Degeneration (AMD): One-Year Results]. / Das klinische Ergebnis eines Therapiewechsels von Ranibizumab und/oder Bevacizumab zu Aflibercept bei neovaskulärer altersabhängiger Makuladegeneration (AMD).

BACKGROUND: The presented study is a retrospective evaluation of switching therapy from ranibizumab and/or bevacizumab to aflibercept in neovascular age-related macular degeneration in patients who had previously given an insufficient response to therapy with ranibizumab and/or bevacizumab. PATIENTS AND METHODS: 96 eyes with neovascular age-related macular degeneration (AMD) were included, which had been pretreated with ranibizumab and/or bevacizumab (T&E), but had responded insufficiently. An injection interval of less than six weeks or permanently persisting intra- and/or subretinal fluid or persistent pigment epithelial detachments (PED) were defined as an insufficient response. The patients were followed for 12 months after switching therapy to aflibercept. The change in central retinal thickness (CRT) was defined as the primary endpoint. Other endpoints were the axial height of PEDs and the injection interval. RESULTS: The primary endpoint, the average CRT, was significantly decreased twelve months after switching therapy to aflibercept (Wilcoxon Nemenyi-McDonald-Thompson post-hoc analysis - 31.36 µm; SD ± 70.64 µm; p < 0.001). Another morphological endpoint, the average axial height of PEDs, also decreased significantly (- 34.10 µm; SD ± 91.90 µm, p < 0.001) from 207.82 µm (SD ± 148.12 µm) at baseline to 173.72 µm (SD ± 132.30 µm) at month 12. Moreover, the average injection interval increased significantly (p < 0.001; Friedman test) from 1.30 months (SD ± 0.19 months) before switching therapy to 1.67 months (SD ± 0.19 months) at month 12 after switching therapy to aflibercept. However, the best corrected visual acuity (BCVA) as a functional endpoint did not significantly improve (+ 0.36 ETDRS letters = 0.0972 p; SD ± 16.94 ETDRS letters). CONCLUSION: In patients with neovascular AMD, who had initially exhibited an inadequate response to ranibizumab and/or bevacizumab, switching therapy to aflibercept improves clinical outcome measures. Besides morphological improvements, such as the decrease of the CRT and the axial height of PEDs, the average injection interval was prolonged. However, visual acuity did not improve.

[100 years after Kienböck's description: review of the etiology of Kienböck's disease from a historical perspective]. / 100 Jahre nach Kienböck: Literaturübersicht über die Ursachenforschung der Mondbeinnekrosen.

Kienböck's disease (KD) leads to collapse of the lunate bone with severe consequences for the wrist function which for some patients may result in occupational invalidity. The many synonyms of KD (aseptic necrosis or avascular necrosis) insinuate that the true etiopathology remains poorly understood. This reviews aims at exploring the level of evidence which brought forward the different hypotheses on the origin of KD. The widespread theories about the origin were formed about 100 years ago but a specific therapy is still not within reach. Although the cause of the disease remains essentially unknown it is officially recognized as an occupational disease in Germany. Empirical attempts to explain the etiopathology are based on compression of the lunate, impaired vascularity through vibration exposition, fracture and dislocation of the lunate from the radiolunate fossa. The level of evidence urges a cautious interpretation of currently discussed hypotheses on the etiology of KD.

[Treatment algorithm for scaphoid nonunion : retrospective case-control study of 208 patients]. / Behandlungsalgorithmus der Kahnbeinpseudarthrose : Eine retrospektive radiologische Fall-Kontroll-Studie von 208 Patienten.

INTRODUCTION: We present a retrospective study on different treatment options for scaphoid nonunion. The results are compared to the literature and a treatment algorithm is proposed. MATERIALS AND METHODS: Based on a retrospective case-control study, 208 patients suffering from scaphoid nonunion were treated between 2000 and 2006. The patients were grouped depending on the localization of the nonunion: proximal (n=10), middle (n=105), or distal (n=93) third. In the presence of a small avascular proximal fragment, a vascularized bone graft from the distal radius was added (n=53). The determination of scaphoid healing was achieved by conventional radiographs or CT scans. RESULTS: Overall scaphoid healing occurred in 89.9% (n=187). For small proximal scaphoid fragments (n=93), we could show healing rates up to 83% (n=77). Using a vascularized bone graft from the distal radius, scaphoid consolidation was achieved in 81% for avascular proximal fragments and recurrent scaphoid nonunion (n=53). CONCLUSION: Using sophisticated treatment options, the prognosis of scaphoid nonunions is very good.

[Primary treatment of complicated flexor tendon injuries of the hand]. / Primärversorgung komplizierter Beugesehnenverletzungen an der Hand.

Complicated flexor tendon injuries are classified into lacerations, avulsions, ruptures, and defects. They are often a challenge for hand surgeons and frequently they present unsatisfactory functional results postoperatively. Lacerations and avulsions are usually treated by pull-out sutures and suture anchors. In ruptures, the causality should be sought. Tendon-linking, transposition and tenodesis/arthrodesis are the domain of rheumatoid arthritis. The primary transplantation of tendons is rarely indicated, ideally in non-contaminated flexor tendon defects in zones III-V with an uninjured surrounding soft tissue situation. Postoperative rehabilitation programs are very the same as in normal flexor tendon injuries.

[Bilateral multifocal pigment epithelial detachments associated with inhaled corticosteroids]. / Bilaterale multifokale Pigmentepithelabhebungen in Assoziation mit inhalativen Kortikosteroiden.

A 37-year-old male patient presented with metamorphopsia and unilateral visual impairment with the presence of hundreds of bilateral avascular retinal pigment epithelial detachments (PEDs). The patient suffered from allergic bronchial asthma which was treated with inhaled corticosteroids. Cessation of corticosteroid treatment resulted in flattening of larger PEDs and subsequent transition to atrophic areas over time while smaller PEDs persisted and spread peripherally over an observation period of 14½ years.

[Histology of the living eye : Noninvasive microscopic structure and functional analysis of the retina with adaptive optics]. / Histologie im lebenden Auge : Nichtinvasive mikroskopische Struktur- und Funktionsanalyse der Netzhaut mit adaptiven Optiken.

Equipping an ophthalmoscope with adaptive optics (AO) offers access to the living human retina with unprecedented spatial resolution. With AO, cellular structures such as the nerve fiber layer, the microvasculature of the smallest retinal capillaries, rod and cone photoreceptors and the mosaic of the retinal pigment epithelium are directly observable. A large number of studies in the normal and diseased retina have already shown that this level of detail offers new insights into disease mechanisms and progression, and promises to identify early disease markers. In conjunction with functional testing of single photoreceptors that is possible with AO microstimulation, a structure-function relationship on the cellular scale is within reach. These technological advances offer new avenues for clinical ophthalmology, interventional efforts, and basic research of the function and dysfunction of vision.

[Hand Therapy in the Treatment of Patients with CRPS]. / Die Handtherapie in der Behandlung des CRPS.

In the modern treatment of CRPS a multidisciplinary concept is firmly established (MMPT, multimodal pain therapy). Besides medical therapy and psychotherapy, physio- and occupational therapy count as basic treatment options. Although physio- and occupational therapy (in the following called hand therapy) are the most important basic treatments, the therapy is hardly standardised and there are few scientific investigations concerning their application. Therefore the purpose of this paper is to present the applied hand therapeutic techniques with regard to function/performance, application and effectiveness, and to derive a suitable treatment algorithm. The techniques used in hand therapy are presented and reviewed in regard to their effectiveness by means of a literature search. It turns out that exercise therapy, manual therapy, graded motor imaging, CO2 baths and occupational therapy have a proven benefit for the patients. Although for many of the treatments reliable evidence-based data are lacking a treatment algorithm was established but there is a strong need for further investigations concerning the therapeutic effectiveness in the treatment of CRPS.

The effect of response bias on recall performance, with some observations on processing bias.

We explored Roediger and Payne's proposal that response bias does not affect recall performance and that it is therefore not necessary to control for response productivity in recall studies. Two initial experiments, contrary to expectation, corroborated Roediger and Payne's findings: Forced recall did not produce more correct recalls than free recall, even though forced recall produced substantially more false alarms than did free recall. However, in succeeding experiments involving pictorial and verbal stimuli, reliable response-bias effects on recall were demonstrated. The stimuli yielding response-bias effects were those associated with higher probabilities of being guessed by chance. In addition, some of the data suggest that processing-bias effects (differential retrieval effort) may be unintentionally induced by instructions and may significantly affect recall memory. Consequently, it is necessary to assess or to control response-bias effects and, possibly, processing-bias effects in recall experiments in which level of recall is of interest.

Enantioselective Michael reactions of chiral secondary enaminoesters with 2-substituted nitroethylenes. Syntheses of trans, trans-2,4-disubstituted pyrrolidine-3-carboxylates

The Michael reaction of chiral 3-substituted secondary enaminoesters with 2-substituted nitroethylenes leads to (Z)-adducts, with good to excellent diastereoselectivity. The nitro group of these adducts was catalytically reduced to give, after cyclization and chiral amine elimination, pyrrolines or pyrrolidines after further reduction. In particular, the syntheses of ethyl (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate are described.

[Plexiform fibrohistiocytic tumour - case report of a rare low-malignant tumour with frequent localisation at the upper limb]. / Plexiformer fibrohistiozytischer Tumor. Fallbericht - Ein seltener niedrig-maligner Tumor mit vorwiegendem Befall der oberen Extremität.

A male child aged nine months was admitted due to a slow growing, painless resistance at the palmar aspect of the proximal phalanx of the index finger. The intraoperative aspect of the tumour showed a yellow to white soft tissue mass with signs of infiltration. After special histopathological stainings, the diagnosis of a plexiform fibrohistiocytic tumour was confirmed. In literature almost 100 cases were reported since first description by Enzinger and Zhang in 1988. In this paper, 41 of 65 described cases showed tumour localization in the upper limb. This is the second case ever published in Germany and the first with localisation to the hand. There is very little clinical experience with this tumour entity. Local recurrence, lymphatic and pulmonal metastases with lethal outcome in rare cases are described. In the presented case, after secondary radical excision of the tumour, the patient has been free of local recurrence and actually in complete remission for 14 months.

[Clinical importance of CMV-infection in German-speaking burn centers]. / Die Bedeutung der Cytomegalievirus-Infektion in deutschsprachigen Verbrennungszentren.

Due to immunosuppression, burn patients are at risk for CMV-infection. By means of a retrospective questionnaire we evaluated the clinical rating and management of CMV-infection in German-speaking burn centers. 41 % of the participating burn centers considered the role of CMV-infection of overall minor importance, 41 % of importance only in intensive care burn patients, 18 % of overall great importance. 70 % of the participating burn centers do not perform CMV-screening at admission. More than 50 % of the participating burn centers consider application of CMV-negative human blood-derived products in CMV-seronegative individuals as essential. At present clinical importance of CMV-infection in burn patients can not be clearly determined. But further prospective studies utilizing recently developed diagnostics seem warranted to the potential influence of CMV-infection on morbidity and mortality in burn patients.

Cutaneous microcirculatory assessment of the burn wound is associated with depth of injury and predicts healing time.

RATIONALE: Current trends for the treatment of deep partial thickness and full-thickness burns include early excision and skin grafting. In this study we retrospectively evaluated the ability of Laser Doppler Flowmetry (LDF), taken within 24h of the burn to predict: (1) burn wound depth and (2) wounds which would heal in less than 21 days. METHOD: The Laser Doppler Flowmeter (O2C, LEA Medizintechnik, Germany) was employed to non-invasively measure the cutaneous microcirculation of 173 selected areas on 28 patients who suffered burns. RESULTS: A distinct association between initial flow (<24h after burn injury) and the clinical assessment of depth of burn wounds was observed. Wounds demonstrating an initial blood flow of >100 AU were, in 93.1% of cases, correctly (positively) predicted for spontaneous healing within 21 days. A blood flow of <100 AU (negatively) predicted in 88.2%, those wounds which would not go on to heal within 21 days. Sequential measurement analysis (<24h, 3 days after injury and 6 days after injury) revealed no significant decrease in skin perfusion velocity or flow rate. CONCLUSION: LDF can provide immediate results for early determination of burn wound depth and is useful in selecting patients for conservative treatment of their burn wounds.

Time course of action and recovery of rocuronium bromide in children during halothane anaesthesia--a preliminary report.

In this preliminary study, two groups of 15 patients, aged 1-4 years and 5-10 years respectively, received one of four doses of rocuronium (0.12, 0.17, 0.22 or 0.27 mg kg-1) and when block was maximal a supplementary dose to bring them all to a total of 0.5 mg kg-1. In half the patients, the block was reversed with atropine and neostigmine at a T1 recovery of 25%. The remainder were allowed to recover spontaneously. The total dose produced a block of 95-100% in all patients. The clinical duration of action was shorter under halothane anaesthesia in children (mean 15 min approximately) than has previously been reported in adults under intravenous anesthesia. Mean spontaneous recovery time from T1 25% to a train-of-four ratio of 0.7 was about 11 min. Neostigmine doubled the rate of recovery. There was a moderate increase in heart rate in the younger age range.

[Dissection of the carotid artery and vertebral artery--diagnosis and therapy]. / Die Dissektion der Arteria carotis und Arteria vertebralis--Diagnostik und Therapie.

Carotid and vertebral artery dissections typically occur in young adults after major trauma, although they can arise spontaneously or after trivial injury. Many patients with carotid dissections have minor symptoms such as a subject bruit or Horner's syndrome. Cephalic pain is also frequent and often inaugural in carotid dissection. However, extracranial dissection is a well recognised cause of ischaemic stroke. The diagnosis of dissection was based on angiographic findings. Noninvasive imaging also allows prompt and reliable diagnosis. Our goal was to demonstrate the spectrum of neuroradiologic (CT, MR and angiographic) findings in craniocervical arterial dissection and compare the diagnostic utility of CT, MR, MR angiography. Clinical data imaging studies, and outcome were reviewed and compared with the results in four patients with carotid artery dissection.

[Evaluating scar development with objective computer-assisted viscoelastic measurement]. / Die Beurteilung der Narbenbildung mit objektivierbarer computerunterstützer viscoelastischer Messung.

In a prospective study we compared the subjective scar assessment by the Vancouver Scar Scale with an objective viscoelastic measurement. Donor sites from the thigh primarily dressed with vaseline gauze (F), biobrane or occlusive dressing(O) were evaluated 0.5 years postoperatively by VSS and with the Cutometer (Courage and Khazaka). VSS of donor sites was 2.74 +/- 0.91 (F), 4.25 +/- 0.77 (B) and 2.57 +/- 0.72(O) (mean +/- sem). All ratings were significant compared to normal mirror-sided skin. Viscoelastic measurements by the Cutometer were near normal compared to uninjured skin. No correlation was found between subscale VSS pliabilty rating and Cutometer readings.