[Extensor tendon injuries at the level of the proximal interphalangeal joint]. / Strecksehnenverletzungen in Höhe des Mittelgelenks.

Closed and open injuries of the extensor mechanism at the proximal interphalangeal (PIP) joint can involve the central slip, the lateral slips or both. They are classified as zone III injuries. All open injuries on the dorsal side of the PIP joint should raise suspicion of an extensor tendon injury that is frequently overlooked. The operative strategy consists of wound revision with extensor tendon suture or refixation of the central slip. Acute closed central slip injuries are clinically diagnosed (Elson test) after ruling out bony injuries to the joint. Nondisplaced avulsions of the central slip insertion or lacerations can be treated nonoperatively by splinting. For displaced avulsions and complex injuries the treatment is surgical. In overlooked injuries a typical deformity (buttonhole/Boutonnière deformity) develops within 1-2 weeks that is characterized by an extension lag of the PIP joint and hyperextension at the distal interphalangeal joint. In early cases, when passive extension is still complete (mobile buttonhole deformity) the central slip can be immediately reconstructed. In fixed deformities complete passive extension of the PIP joint has to be restored before surgery by hand therapeutic measures or PIP joint release. Depending on the pattern of the injury and the resulting defects, a number of reconstructive techniques have been established that are summarized in this article. The functional results can be limited by tendon adhesions, imbalance within the reconstructed extensor apparatus and stiff joints that can all restrict the range of motion. Therefore, active rehabilitation protocols are mandatory for optimal results.

The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In-Situ Measurements in the Tropical Lower Stratosphere.

Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that may be intentionally enhanced in the future to offset greenhouse gases (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in maintaining background SAs has been debated for decades without in-situ measurements of SO2 at the tropical tropopause to inform this issue. Here we clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements to evaluate climate models and satellite retrievals. We then use the observed tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across the tropical tropopause. These analyses show that the tropopause background SO2 is about 5 times smaller than reported by the average satellite observations that have been used recently to test atmospheric models. This shifts the view of SO2 as a dominant source of SAs to a near-negligible one, possibly revealing a significant gap in the SA budget.

[Acute scaphoid fractures : Management under consideration of the new S3-level guideline]. / Die frische Skaphoidfraktur : Management unter Berücksichtigung der neuen S3-Leitlinie.

BACKGROUND: Scaphoid fractures represent the most common carpal fractures and are often problematic and frequently lead to nonunion with osteoarthritis and collapse of the wrist. The reasons for the nonunion are manifold. Therefore, the main goal of diagnosis and therapy of acute fractures is to achieve bony union and to restore the anatomic shape of the scaphoid. In the long run, only this can preserve the normal function of the wrist. METHODOLOGY: The given recommendations are based on the new S3-level guideline of the AWMF (Association of the Scientific Medical Societies). This guideline was established with involvement of all relevant medical societies based on a comprehensive and systematic review of the literature and after a process of formal consent. The focus of the guideline is recommendations regarding diagnosis and therapy of acute scaphoid fractures. MAIN STATEMENTS: After careful clinical examination consequent imaging must be performed, starting with X­rays in three standard projections. Computed tomography is indispensable for proof of a fracture and for therapy planning. The classification of Herbert and Krimmer is based on the CT under special consideration of instability and displacement of the fracture. Thus, indication for operative and non-operative treatment is mainly CT-dependent. Non-operative treatment may be indicated only for stable fractures (type A). However, operative treatment is strongly recommended for all unstable fractures (type B). For fixation, double-threaded headless screws are preferred. The operative technique depends on the fracture morphology. CONCLUSION: Diagnosis and therapy of acute scaphoid fractures are primarily aimed at the prevention of nonunion and arthritic carpal collapse with painful impairment of the wrist function. To achieve this, the S3-level guideline contains explicit recommendations.

Synthesis and characterization of novel zinc phthalocyanines as potential photosensitizers for photodynamic therapy of cancers.

Two novel zinc phthalocyanines (Pcs): tetramethyl tetrakis-2,(3)-[(4-methyl-2-pyridyloxy)phthalocyaninato] zinc(II) (4) and (the negatively charged form) tetrakis-2,(3)-[(3-carboxylicacid-6-sulfanylpyridine)phthalocyaninato] zinc(II) (5), water soluble by virtue of their ionic substituent groups were synthesized. The spectroscopic properties of both compounds were determined and their photodynamic activities were investigated in a human tumor cell model. In aqueous media the two peripherally substituted water soluble Pcs are highly aggregated. The phototoxic activity of the two novel Pcs (Pc 4 and Pc 5; 0-20 µM) was shown to be time- and dose-dependent in human pancreatic carcinoid BON cells, leading to a reduction of tumor cells of >80% compared to the controls. The effectiveness of the treatment appeared to be attenuated by the aggregation of Pcs under aqueous conditions. Interestingly, even those cells that were not immediately killed by the photoactivated photosensitizer seemed to be affected by the Pc photodynamic activity, as a single PDT induced long-lasting effects on cell survival. Even 4 days after PDT, the number of surviving cells did not re-increase or still dropped, as compared to control cells. The underlying mechanism of this observation has to be deciphered in future investigations.

[Carpometacarpal fractures and fracture dislocations of rays 2-5]. / Karpometakarpale Frakturen und Luxationsverletzungen des 2. bis 5. Strahls.

BACKGROUND: Fractures and fracture dislocations of carpometacarpal joints 2-5 may be easily overlooked. This can be explained by often subtle clinical and radiographic signs. In case of clinical suspicion with apparently normal standard x-rays, a computed tomography with thin slices should be promptly performed. Therapy is predominantly operative and aims at anatomic reduction and reconstruction of joint congruity. TREATMENT: To facilitate treatment decisions, especially concerning closed or open fixation, we have defined 3 pathomorphological patterns (types I-III). Decision criteria are sagittal or coronal plane of fracture, degree of destruction of the articular surface, and radial or ulnar location of the injury. Following operative therapy, early mobilization of all finger joints should be performed.

[Injuries of the proximal interphalangeal joint]. / Verletzungen der Mittelgelenke.

BACKGROUND: Injuries of the proximal interphalangeal joint (PIP joint) are common. They are frequently underestimated by patients and initial treating physicians, leading to unfavorable outcomes. Basic treatment includes meticulous clinical and radiological diagnosis as well as anatomical and biomechanical knowledge of the PIP joint. TREATMENT: In avulsions of the collateral ligaments and the palmar plate with or without involvement of bone, nonoperative treatment is preferred. Operative stabilization is reserved for large displaced bony fragments or complex instabilities. In central slip avulsion or rupture, osseous refixation, suture, or reconstruction is common and nonoperative treatment is limited to special situations like minimally displaced avulsions. In basal fractures of the middle phalanx, elimination of joint subluxation and restoration of joint stability are priority. If the fragments are too small for fixation with standard implants, therapeutic alternatives include refixation of the palmar plate, dynamic distraction fixation, percutaneous stuffing, or replacement by a hemihamate autograft. Early motion is initiated regardless of the treatment regime. Undertreatment leads to persistent swelling, instability, and limited range of motion, which are difficult to treat. Contributing factors are unnecessary immobilization, immobilization in more than 20° flexion or transfixation by K-wires. For residual limitations, nonoperative treatment with physiotherapists and splinting is first choice. Operative treatment is reserved for persistent flexion/extension contractures persisting for more than 6 months, as well as reconstructions in boutonniere and swan neck deformity and salvage procedures for destroyed joints.

[Complex fragmentation of the distal radial articular surface. Reconstruction with subchondral Kirschner wires and bone grafts]. / Komplexe Fragmentation der distalen Radiusgelenkfläche. Rekonstruktion durch subchondrale Kirschner-Drähte und Knochentransplantate.

BACKGROUND: Complex fragmentation of the distal radial articular surface often results in three major problems: some fragments are too small for stabilisation by standard plates or screws; in addition, substantial loss of articular surfaces and metaphyseal/subchondral bony defects frequently occur. MATERIAL AND METHODS: To solve these problems the following strategy was developed: the fixation of small articular fragments was performed by small K-wires that were placed subchondrally and countersunk in the bone. In case of lost articular surfaces a silicone foil was inserted intra-articularly to induce a cartilage-like tissue. Bony defects were replaced by iliac crest bone grafts. Additional stability was achieved by dorsal and volar plate fixation or bridge plating. RESULTS: An average of 53° of extension, 44° of flexion, 74° of pronation, and 66° of supination were achieved. The grip strength was an average of 61% of that in the contralateral limb. The average radiographic measurements were -5° of palmar inclination, 21° of ulnar inclination, and 0 mm of positive ulnar variance. A good or excellent functional result was achieved for five of seven wrists according to the rating system of Gartland and Werley. According to the modified Mayo Wrist Score four of five wrists achieved a good and one a fair result.The DASH Score averaged 19 (6-59) points. CONCLUSIONS: The applied treatment resulted in stable, mobile wrists with reasonable alignment and nearly even articular surfaces. The functional results were similar to those reported by other authors for less complex distal radius fractures. This strategy seems to be a rational approach to the reconstruction of severely comminuted intra-articular fractures of the distal radius.

Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer.

BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.

Apoptosis-modulating drugs for improved cancer therapy.

Resistance to cell death induction has been recognized as a hallmark of cancer. Increasing understanding of the underlying molecular events regulating different cell death mechanisms like apoptosis, endoplasmic reticulum stress, autophagy, necroptosis and others has opened new possibilities for targeted interference with these pathways. While conventional chemotherapeutic agents usually inhibit cell cycle progression, DNA replication or mitosis execution, novel agents like small molecule kinase inhibitors also target survival-related kinases and signaling pathways and contribute to overcome resistance to chemotherapy and apoptosis. Additionally, antibodies targeting cellular death receptors have been described to specifically target tumor cells only. This review briefly highlights the pathways involved in (apoptotic) cell death and summarizes the current state of development of specific modulators of cell death and how they can help to improve the tolerability of chemotherapy regimens and increase survival rates in patients with advanced cancer diseases.

[Collateral ligament injuries of the metacarpophalangeal joints]. / Kollateralbandverletzungen der Fingergrundgelenke.

Collateral ligament injuries of the metacarpal joints of the fingers are rare conditions. The injury should be diagnosed by clinical investigation and standard radiographs. Leading symptoms are local tenderness and joint instability. Instability is verified by clinical stress testing of the metacarpophalangeal joint in 90° of flexion. In Grade I injuries stability is preserved due to ligament attenuation or small partial tears. Grade II injuries show laxity with firm endpoint according to incomplete tear. In Grade III injuries instability without endpoint can be found as a result of complete tears. Radiographs may show avulsed bone fragments.In Grade I and II tears or non- displaced avulsion fragments treatment is conservative with buddy taping for 6 weeks. In case of persistent instability or grade III tears suturing or refixation of the ligament are performed. Small avulsion fragments are removed and the ligament is fixed to the bone. Greater avulsion fragments are fixed by suitable small implants. Adequate treatment will lead to reliable good results. Even in chronic tears reconstruction with local material or tendon transplants is usually successful.

[Therapy of triangular fibrocartilage complex lesions]. / Therapie von Läsionen des "triangular fibrocartilage complex".

The triangular fibrocartilage complex (TFCC) represents an important anatomical structure interposed between the ulnar carpus and the distal ulnar. Injuries and degenerative changes of the TFCC are of high clinical relevance and there are numerous treatment options available based on different concepts and which are being used to varying extents. The aim of this systematic review was to evaluate the effectiveness of different therapies for lesions of the TFCC. Studies on TFCC lesions were systematically reviewed, classified into evidence levels and selected according to predefined criteria. A total of 259 publications were identified as being potentially relevant and finally 35 studies could be included in the review. In addition, a survey was performed among German hand surgeons in order to identify commonly used procedures for TFCC lesions in Germany. The classification of Palmer is mostly used both in the literature and in Germany and therapeutic decisions are predominantly based on this classification. The systematic review revealed some common treatment strategies for traumatic and degenerative lesions. Generally, the level of evidence was poor for all identified publications. For this reason, evidence-based recommendations for the treatment of TFCC lesions could not be derived from the literature. There was broad consent between the results of the literature review and the survey.

[Current concepts in the treatment of mallet fractures of the distal phalanx]. / Aktuelle Konzepte in der Therapie der dorsalen Endgliedbasisfraktur.

Articular fractures of the dorsal part of the distal phalanx may result in a painful dysfunction and a bothersome deformity of the distal interphalangeal joint. For this injury multiple treatment procedures exist. We performed a survey among German hand surgeons and a review of the literature in order to present current concepts of treatment and to verify the feasibility of a randomized trial. There is a tendency to prefer conservative treatment options. The indication for operative treatment depends on size and displacement of the articular fragment as well as on subluxation of the joint. Operative techniques vary widely and the comparability of their results is restricted. Complications more often occur after operative treatment. The type of injury and the individual demands of the patient are the most relevant factors for the choice of treatment. From the results of the survey and the review of the literature, a randomized trial of conservative and operative treatment has to be considered as a challenge.

[Diagnosis and treatment of radiocarpal fracture dislocations]. / Diagnostik und Therapie von radiokarpalen Luxationsfrakturen.

In contrast to the common intra- or extra-articular fractures of the distal radius, radiocarpal fracture dislocations are rare injuries. Concerning this issue, only a small number of publications can be found. Nevertheless, it is important to be informed about this injury since prompt operative treatment is often required and immobilization alone will not be sufficient. Sometimes, radiocarpal fracture dislocations are combined with carpal injuries. In such cases, both the radiocarpal dislocation and carpal injury have to be treated. Diagnostic difficulties can lead to misinterpretation or underdiagnosis. Insufficient reduction and fixation may result in joint incongruity and subsequent osteoarthritis. Reconstruction of the radiocarpal ligaments is a substantial part of operative treatment.

[Treatment strategy for carpometacarpal fracture dislocation]. / Behandlungsstrategie bei karpometakarpalen Luxationsfrakturen.

Carpometacarpal (CMC) fracture dislocations of the 2nd through 5th ray are rare injuries whose extent is regularly underestimated in the initial radiographic evaluation of the hand. Obtaining a computed tomography scan is imperative due to the radiographic underrepresentation of the full bone and joint injury. Restoration of bone and joint anatomy of the affected region is of paramount import to prevent joint deterioration and loss of hand durability and dexterity. Early surgical intervention can lead to good functional results. Different operative treatment strategies exist with a common approach being Kirschner wire, screw or plate fixation after closed or open fracture reduction and joint relocation.

Novel compounds with antiangiogenic and antiproliferative potency for growth control of testicular germ cell tumours.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cause of death from solid tumours in young men and especially for platinum-refractory patients novel treatment approaches are urgently needed. Using an in silico screening approach for the detection of novel cancer drugs with inhibitory effects on the tyrosine kinase activity of growth factors (e.g., VEGFR, PDGFR), we identified two compounds (HP-2 and HP-14) with antiangiogenic and antiproliferative potency, which were evaluated in endothelial cell models and TGCT cells. RESULTS: HP-2 and HP-14 effectively inhibited the growth of VEGFR-2-expressing TGCT cell lines (Tera-1, Tera-2 and 2102EP) and endothelial cell models, while they failed to supress the growth of VEGFR-2-lacking tumour cells. cDNA-microarrays revealed an inhibition of the expression of several growth factor receptors and related signal transduction molecules. Vascular endothelial growth factor (VEGF)-induced cell migration was also potently inhibited. Cell cycle-regulating proteins such as p21 and p27 were upregulated, leading to an S-phase arrest. Additional in vivo evaluations confirmed the antiangiogenic potency and good tolerability of the novel substances. CONCLUSION: Our data show that the identified novel compounds inhibit the growth of TGCT cells and decrease angiogenic microvessel formation. The mode of action involves cell cycle arresting effects and changes in the expression pattern of several angiogenic genes. The novel compounds may qualify as new candidates for targeted treatment of TGCT and merit further evaluation.

[Treatment of carpal fractures. Recommendations of the Hand Surgery Group of the German Trauma Society]. / Behandlung von Handwurzelfrakturen. Empfehlungen der Sektion Handchirurgie der Deutschen Gesellschaft für Unfallchirurgie.

The primary goal in the treatment of carpal fractures is the preservation of a painless wrist function. Scaphoid fractures are the most common carpal fractures and when such a fracture is clinically suspected CT or MRI scans are usually advisable. Only stable and non-displaced scaphoid fractures can be treated conservatively, all other fractures require internal fixation with restoration of normal anatomy. Second most common are fractures of the triquetrum which can occur as chip avulsions of the dorsal rim and are usually treated symptomatically. Fractures of the body of the triquetrum should be treated according to the degree of instability and displacement. This is virtually true for all carpal bones. Perilunate fracture dislocations of the carpus deserve special attention. In these severe injuries a fracture line can run through all carpal bones but the scaphoid is mostly affected. Accurate reduction and internal fixation by screws and K-wires are indicated not only in these cases, but also in carpometacarpal fracture dislocations.