Haarfarbe und Haarfarbstoffe

Ohne Zusammenfassung     

Clinical approach to normal intraocular pressure glaucoma

Normal intraocular pressure (IOP) glaucoma is a clinical condition characterized by pathologic optic nerve excavation and visual field impairment, defined as optic neuropathy with certain features of a disease known as glaucoma. Glaucomatous optic nerve lesion is characterized by optic disk excavation or depression, however, this feature may greatly vary. The level of IOP is considered only one of the multiple risk factors involved in the disease development. In normal IOP glaucoma, papillary lesions and visual field impairments may differ from those occurring in primary open-angle glaucoma. In modern ophthalmology, the terminology has been modified, so the term low IOP glaucoma has been replaced by the term normal IOP glaucoma. It is now believed that various factors play a role in the development of glaucomatous optic neuropathy in normal IOP glaucoma and show variable interference depending on IOP level. Additional studies are needed to define these interactions and their impact on the mechanism of glaucomatous excavation. This will hopefully pave the way to new therapeutic approaches and help in clinical decisions concerning the prognosis and treatment of individual patients.     

Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors

While the field of cancer genetics has enjoyed a great deal of attention among cancer researchers in the last few decades, the appreciation of cancer epigenetics is more recent, -owing to the fact that epigenetic mechanisms have emerged as key mechanisms in cancer development. All critical changes in cancer cells, such as silencing of tumour-suppressor genes, activation of oncogenes and defects in DNA repair, are caused not only by genetic but also by epigenetic mechanisms. Epigenetic events can affect many steps in tumour development; therefore, better understanding of epigenetic mechanisms is fundamental to our ability to successfully prevent, diagnose and treat cancer. Various environmental and dietary agents and lifestyles are suspected to be implicated in the development of a wide range of human cancers by eliciting epigenetic changes, though the contribution of epigenetic mechanisms to a given human cancer type and the precise targets of epigenetic alterations during cancer development are largely unknown. The major obstacle in establishing a relationship between epigenetic changes and exposure to dietary, lifestyle and environmental factors and cancer is the fact that studies are typically too small and lack statistical power to identify the interactions between epigenetic changes and exposures. Tremendous advances in our understanding of basic epigenetic mechanisms and rapid progress that is being made in developing new powerful technologies, such as those for sensitive and quantitative detection of epigenetic changes as well as for genome-wide analysis (epigenomics), hold great promise that these issues may be addressed in near future. Therefore, experimental evidence on the precise role of epigenetic changes induced by environment, diet and lifestyle is eagerly awaited.     

Primary leptomeningeal melanomatosis successfully treated with PD-1 inhibitor pembrolizumab: A case report

Rationale:Primary leptomeningeal melanoma is an extremely rare disease of the central nervous system. There are no standard treatment protocols with a poor prognosis in very few reported cases. Immunotherapy in primary brain melanoma has not been successfully applied so far.Patient concerns:We describe a female patient 72-year-old diagnosed in the Neurosurgery Department which presented with generalized seizures.Diagnoses:Histological examination confirmed atypical melanocytes immunohistochemically positive for melan A, HMB45 and S-100 protein in the meninges, BRAF V600E negative. Dermatological, ophthalmological examinations, and 18-FDG PET/CT were negative.Interventions:The patient was successfully treated with pembrolizumab 2 mg/kg every 3 weeks for 2 years.Outcomes:The disease was stable for 2 years and the patient had no significant toxicity.Lessons:Our report describes durable intracranial tumor response suggesting the efficacy of PD-1 inhibitor pembrolizumab for central nervous system primary leptomeningeal melanoma.     

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells.     

Rare complication of breast cancer irradiation: postirradiation osteosarcoma

Radiation-induced osteosarcoma is a rare complication of radiation therapy for breast cancer. The authors present a 60-year-old patient in whom osteosarcoma of the chest wall developed 5 years after modified radical mastectomy and radiation therapy for breast cancer. One year after resection of the chest osteosarcoma, metastasis to the contralateral axillary lymph nodes developed and these were removed. Radiation-induced osteosarcoma is difficult to treat and has a poor prognosis, thus early diagnosis is necessary for optimal treatment.     

Seasonal variations of polychlorinated biphenyls in ambient air in Zagreb,Croatia

Levels of polychlorinated byphenils (PCBs) were monitored continuously in Zagreb between June 1999 and February 2000 and analysed qualitatively and quantitatively using high resolution gas chromatography (HRGC). Total PCBs were determined with respect to Aroclor 1260, which was used as the standard reference. The concentrations of PCBs ranged from 1.6 to 136 pg/m3 and were higher in warmer seasons (temperatures above 10 degrees C; 5.1-136 pg/m3) than in colder seasons (temperatures from -10 degrees C to about 10 degrees C; PCB range: 1.6-23.5 pg/m3). The increase in PCBs concentration with temperature followed an exponential curve.     

Increased resistance to anticancer therapy of mouse cells lacking the poly(ADP-ribose) polymerase attributable to up-regulation of the multidrug resistance gene product P-glycoprotein

Mouse embryo fibroblasts lacking poly(ADP-ribose) polymerase (PARP)-1 express a barely detectable level of wild-type (wt) p53 protein. Doxorubicin at concentrations activating wt p53 in normal mouse embryo fibroblasts failed to induce it in mutant cells. wt p53 was only activated in response to a 10-fold higher doxorubicin dose. Treatment with higher doxorubicin concentrations was cytotoxic for normal but not for PARP-1 -/- cells. The latter was also resistant to other anticancer agents. The increased resistance of mutant cells to drugs resembled a unique phenomenon known as multidrug resistance (MDR). Interestingly, the MDR gene product P-glycoprotein was clearly up-regulated in PARP-1-deficient cells as compared with normal counterparts. Pretreatment with verapamil reversed the MDR phenotype.     

Interexaminer repeatability of antidromic ulnar sensory nerve conduction velocity measurements

OBJECTIVE: To determine the interexaminer repeatability of the ulnar antidromic sensory nerve conduction velocity (NCV). DESIGN: Test-retest design. Based on a randomization list of various combinations and sequences from 2 of a total of 3 examiners, the measurement was repeated within half an hour by a second examiner blinded to the results of the first examiner. SETTING: Outpatient department. PARTICIPANTS: Twenty-four consecutive healthy subjects (mean age, 38 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (ICC) and the coefficient of repeatability (CR) were determined for the below elbow to wrist (BE-to-W), above elbow to below elbow (AE-to-BE), and axilla to above elbow (AX-to-AE) segments. RESULTS: The ICC was .42 for the BE-to-W, .15 for the AE-to-BE, and -.05 for the AX-to-AE segment. The CR was 12.2m/s for the BE-to-W, 16.2m/s for the AE-to-BE, and 21.4m/s for the AX-to-AE segment. CONCLUSIONS: During the assessment of the antidromic sensory NCV of the ulnar nerve, a moderate amount of interexaminer variability must be taken into account for the BE-to-W segment. More proximally, an extremely large amount of interexaminer variability must be taken into account. This calls into question the usefulness of the antidromic ulnar sensory NCV for the AX-to-AE and AE-to-BE segments.     

Heel reconstruction with an iliac osteocutaneous free flap: 10-year follow-up

During the Homeland War in Croatia, many civilians suffered from war wounds of the extremities. Explosive war wounds create composite and devastating injuries mainly by high-energy transfer to the tissue. We present an early reconstruction of explosive heel wound with an iliac osteocutaneous free flap with late follow-up result.