NF1 mutations in conjunctival melanoma.

BACKGROUND: Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas remain incompletely understood. METHODS: A large cohort of 63 conjunctival melanomas was screened for gene mutations known to be important in other melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with patient prognosis. RESULTS: Frequent mutations in genes activating the MAP kinase pathway were identified. NF1 mutations were most frequent (n = 21, 33%). Recurrent activating mutations were also identified in BRAF (n = 16, 25%) and RAS genes (n = 12, 19%; 11 NRAS and 1 KRAS). CONCLUSIONS: Similar to cutaneous melanomas, conjunctival melanomas can be grouped genetically into four groups: BRAF-mutated, RAS-mutated, NF1-mutated and triple wild-type melanomas. This genetic classification may be useful for assessment of therapeutic options for patients with metastatic conjunctival melanoma.

[Kikuchi-Fujimoto's disease and adult-onset Still's disease. A rare co-occurence]. / Kikuchi-Fujimoto-Syndrom und adulter Morbus Still. Eine seltene Koinzidenz.

Kikuchi-Fujimoto's disease and adult-onset Still's disease are rare inflammatory conditions with overlapping clinical features. Adult-onset Still's disease causes high fevers, a typical salmon-colored rash, and joint pain. The principal symptom of Kikuchi's disease is cervical lymphadenopathy with typical histopathological features including extensive necrosis of the involved lymph nodes. Here, we report on a rare case of concurrent adult-onset Still's disease and Kikuchi-Fujimoto syndrome in a young Caucasian patient.

[Recurrent leg ulcers due to livedoid vasculopathy: successful treatment with low-molecular-weight heparin]. / Rezidivierende ulzerationen bei livedovaskulopathie: erfolgreiche behandlung mit niedermolekularem heparin.

HISTORY AND ADMISSION FINDINGS: A 50-year-old women had suffered from recurrent and extremely painful ulcerations of both legs and the back of her feet for about 3 weeks. The clinical examination showed multiple hemorrhagic and bizarre configured ulcerations with a surrounding livid-erythematous discoloration, hyperpigmentation and extensive atrophie blanche. INVESTIGATIONS: Neither instrument-based nor serological tests revealed specific pathological findings. Histological results from the border area of the ulceration confirmed the diagnosis of livedoid vasculopathy. TREATMENT AND COURSE: A systemic treatment with low-molecular-weight heparin was initiated, resulting in a rapid pain reduction and complete healing of the ulcerations after some weeks of therapy. CONCLUSION: This case report demonstrates that unusual entities like livedoid vasculopathy should be considered as rare causes for recurrent leg ulcers because different underlying etiologies need different specific treatment strategies. Until now treatment for patients with livedoid vasculopathy has not been standardized but anticoagulative therapy with low-molecular-weight heparin is considered to be one treatment of first choice.

Evaluation of bovine zona pellucida characteristics in polarized light as a prognostic marker for embryonic developmental potential.

It has previously been demonstrated that zona pellucida imaging of human oocytes using polarized light microscopy is a clinically applicable method for the noninvasive assessment of oocyte quality. This study was designed to investigate whether zona pellucida characteristics of bovine oocytes and zygotes in polarized light may similarly serve as a useful marker for developmental competence in bovine reproductive biotechnologies. Zona birefringence intensity parameters of 2862 oocytes/zygotes were objectively evaluated with an automatic analysis system and correlated with oocyte/zygote quality. In detail, immature oocytes of good quality assessed with brilliant cresyl blue staining showed significantly lower zona birefringence than poor-quality counterparts (P<0.001). After in vitro maturation and classification according to maturational status, the birefringence intensity parameters were significantly different in those oocytes that reached metaphase II compared with arrested stages (P<0.001). Following either parthenogenetic activation or IVF with subsequent in vitro culture in a well-of-the-well system until day 9, superior development as determined by cleavage, blastocyst formation, and hatching ability was associated with lower zona birefringence intensity parameters. When early zygote-stage embryos were selected and assorted in groups based on zona birefringence (high/medium/low), the group of embryos derived from high-birefringence zygotes displayed a significantly compromised developmental potential compared with low-birefringence zygotes. These results clearly show that developmentally competent bovine oocytes/zygotes exhibit lower zona birefringence intensity parameters. Therefore, birefringence imaging of zona pellucida is a suitable technique to predict bovine preimplantation embryo development.

Oocyte zona birefringence intensity is associated with embryonic implantation potential in ICSI cycles.

A retrospective study recently showed that oocytes presenting with a high birefringence of the inner zona layer were more often associated with conception cycles. To further investigate these findings, a prospective study was conducted between September 2005 and September 2006 including intracytoplasmic sperm injection (ICSI) cycles presenting with at least two embryos for transfer. Using a polarization imaging system, oocytes were classified prior to ICSI treatment as having either a high zona birefringence (HZB) or a low zona birefringence (LZB) of the zona pellucida. Using zona birefringence as the only selection criterion, two fertilized oocytes, preferably derived from HZB oocytes, were selected for further culture and transfer. The required criteria were met by 135 ICSI cycles (124 patients; 34.9 +/- 4.1 years of age). Embryos for transfer were used in 20 cycles derived from HZB/HZB oocytes, in 50 cycles from HZB/LZB oocytes and in 65 from LZB/LZB oocytes. The corresponding implantation (P < 0.025), pregnancy (P < 0.005) and live birth (P < 0.025) rates were significantly different between HZB/HZB and HZB/LZB versus LZB/LZB group. Embryo development was superior in embryos derived from HZB oocytes. This study concludes that oocyte zona birefringence is a good selection criterion and a good predictive criterion for embryo implantation potential.

N1,N10-ditigloylspermidine, a novel alkaloid from the seeds of Ipomoea nil.

A novel spermidine alkaloid, N1,N10-ditigloylspermidine (1), has been isolated from the seeds of Ipomoea nil (L.) Roth (Convolvulaceae). Structural elucidation was achieved by EIMS, HRMS, 1H NMR, and 13C NMR spectroscopy.

Iseluxine: a novel isoquinolinone alkaloid from Iseia luxurians.

A novel isoquinolinone alkaloid, iseluxine (1), has been isolated from the epigeal parts of Iseia luxurians (MORIC.) O'DONELL (Convolvulaceae), a climber indigenous to the tropical Americas. Structural elucidation was achieved by HRMS, 1H NMR, 13C NMR, and HMBC spectroscopy. N- and/or O-methyl derivatives of 1 are already known from certain Magnoliidae families, e.g., the Fumariaceae, the Lauraceae, or the Papaveraceae. Iseluxine, the "missing link" in the biosynthesis of these methyl derivatives from dopamine, is the first isoquinolinone alkaloid characterized by a catechol substructure.