No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case–control study

Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations of polymorphisms in genes coding for vitamin D metabolism-related proteins (1α-hydroxylase [CYP27B1], 1,25(OH)(2)D-24hydroxylase [CYP24A1], vitamin D-binding protein [VDBP]) and cancer risk are scarce, especially with respect to melanoma. Mainly VDR polymorphisms regarding melanoma risk and prognosis were examined although other vitamin D metabolism-related genes may also be crucial. In our hospital-based case-control study including 305 melanoma patients and 370 healthy controls single nucleotide polymorphisms in the genes CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs1155563, rs7041), and VDR (rs757343, rs731236, rs2107301, rs7975232) were analyzed for their association with melanoma risk and prognosis. Except VDR rs731236 and VDR rs2107301, the other six polymorphisms have not been analyzed regarding melanoma before. To further improve the prevention as well as the treatment of melanoma, it is important to identify further genetic markers for melanoma risk as well as prognosis in addition to the crude phenotypic, demographic, and environmental markers used in the clinic today. A panel of genetic risk markers could help to better identify individuals at risk for melanoma development or worse prognosis. We, however, found that none of the polymorphisms tested was associated with melanoma risk as well as prognosis in logistic and linear regression models in our study population.     

Prenatal diagnosis and treatment planning of congenital heart defects—possibilities and limits

Background  Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation. Data sources  PubMed database was searched with terms of “congenital heart defects”, “fetal echocardiography” and “neonatal cardiac surgery”. Results  At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%–95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases. Conclusion  The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.     

Ocular manifestations of antiphospholipid (Hughes)' syndrome--minor features?

The ocular manifestations are described in autoimmune disease, being most common associated with systemic lupus erythematosus, scleroderma, rheumatoid arthritis, insulin-dependent diabetes mellitus, and dermatomyositis. Nonetheless, the antiphospholipid syndrome is a relatively newly recognized autoimmune disorder. Ocular conditions in which to consider antiphospholipid syndrome include amaurosis fugax, transient ischemic attack, retinal haemorrhages and cotton wool spots, central retinal vein and artery occlusion, anterior ischemic optic neuropathy, ophthalmic and cilioretinal artery occlusions. Ocular features due to antiphospholipid antibodies - induced thrombosis should be treated with anticoagulant drugs. In opposition, for the treatment of ocular features due to immunological mechanisms such as vasculitis, immunosuppressants seem to be more suitable. The aim of this article is to underline the mainly ocular features of Hughes' syndrome and for the most part attention should be paid to the patients with central retinal vascular occlusion with no cause but most likely caused by lupus anticoagulant.     

Ocular migraine and antiphospholipid antibodies--where we stand?

There is no doubt that ocular migraine also known as retinal migraine or ophthalmic migraine should not to be confused with ophthalmoplegic migraine. The hallmark of ocular migraine is the unilateral visual loss or "monocular transient loss of vision" associated or followed by the headache. Better safe than sorry, therefore an ophthalmologic examination during the migraine attack is the most diagnostic method. age with typical history for ocular migraine. Importantly supportive data sustain that different neuro-ophthalmologic manifestations as amaurosis fugax, retinal vascular thrombosis and optic neuropathy, may be considered as the ocular hallmarks of the Hughes's syndrome. Clues for the evaluating of antiphospholipid antibodies include recurrent thrombosis especially in young people, recurrent fetal loss, and thrombocytopenia. There are no studies that focus exclusively on the prophylaxis of ocular migraine. Ocular features due to antiphospholipid antibodies - induced thrombosis or Hughes's syndrome should be treated with anticoagulant therapy.     

Biological properties of 4-methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate (ADAP)

OBJECTIVE: 4-Methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate (ADAP) is a potential antitumor compound because of its DNA and RNA intercalating ability. In this study, cellular uptake, intracellular distribution as well as mechanism of action, antitumor activity in vitro and toxicity in vivo of ADAP were investigated. METHODS: Based on the fluorescence properties of ADAP, its entry and distribution into live cells were analyzed by fluorescence microscopy. The in vitro antiproliferative activity was determined using MTT test. For screening of topoisomerase II-targeted effects of ADAP, the cell-free assay and immunoband depletion assay were used. Expression of the genes c-mos, c-N-ras, c-Ki-ras, c-H-ras, p53 and caspase 3 in Caco-2 cells treated with ADAP was examined by RT-PCR. Toxicity in vivo was determined using C3HHf/Bu Zgr/Hr mice treated by single or multiple doses of ADAP at a concentration of 25 mg/kg. RESULTS: ADAP in muM concentrations entered into MIAPaCa-2 cell's cytoplasm in 5 min and into nuclei in 60 min after administration. Intracellular distribution of ADAP depended on the period of treatment time. ADAP (0.1-100 muM) strongly inhibited the growth of both mouse (FsaR, SCCVII) and human tumor cells (HeLa, Caco-2, HT-29, MIAPaCa-2, HBL, HEp-2, SW620, MCF-7) compared to its weak cytotoxicity on controls and normal cells (WI38). Results of both topoisomerase II assays showed that ADAP is not a topoisomerase II poison. Expression of investigated genes was dependent on the incubation time, except for p53 and c-H-ras. Morphological changes in tissues and organs of mice were not observed. Results of patohistological analysis have been confirmed by hematological and clinical-chemical analysis of blood of treated and non-treated animals. CONCLUSION: ADAP is a strongly bioactive compound with antitumor potential in vitro. The antitumor potential in vivo remains to be identified.     

Wi-Fi Technology and Human Health Impact: A Brief Review of Current Knowledge

An enormous increase in the application of wireless communication in recent decades has intensified research into consequent increase in human exposure to electromagnetic (EM) radiofrequency (RF) radiation fields and potential health effects, especially in school children and teenagers, and this paper gives a snap overview of current findings and recommendations of international expert bodies, with the emphasis on exposure from Wi-Fi technology indoor devices. Our analysis includes over 100 in vitro, animal, epidemiological, and exposure assessment studies (of which 37 in vivo and 30 covering Wi-Fi technologies). Only a small portion of published research papers refers to the “real” health impact of Wi-Fi technologies on children, because they are simply not available. Results from animal studies are rarely fully transferable to humans. As highly controlled laboratory exposure experiments do not reflect real physical interaction between RF radiation fields with biological tissue, dosimetry methods, protocols, and instrumentation need constant improvement. Several studies repeatedly confirmed thermal effect of RF field interaction with human tissue, but non-thermal effects remain dubious and unconfirmed.Key words: exposure to RF fields, e-school, radiofrequency, SAR     

Posterolateral lumbar spine fusion with INFUSE bone graft.

BACKGROUND CONTEXT: INFUSE has been proven effective in conjunction with threaded cages and bone dowels for single-level anterior lumbar interbody fusion (ALIF). The published experience with posterolateral fusion, although encouraging, utilizes a significantly higher dose and concentration of recombinant human bone morphogenic protein-2 (rhBMP-2) and a different carrier than the commercially available INFUSE. PURPOSE: To present an assessment of fusion rate for posterolateral spine fusion with INFUSE Bone Graft. STUDY DESIGN/SETTING: Retrospective review of patients treated using INFUSE in posterolateral spine fusion in a single institution. PATIENT SAMPLE: 91 patients with minimum 2-year follow-up who underwent posterolateral spine fusion using INFUSE as an iliac crest bone graft (ICBG) substitute. OUTCOME MEASURES: Fusion rate based on fine-cut computed tomographic (CT) scans with sagittal and coronal reconstructions. METHODS: Fusion was performed using one large INFUSE kit (12 mg rhBMP-2, 1.5 mg/mL), which was prepared according to the manufacturer's instructions. The INFUSE sponge was wrapped around the local bone or graft extender and placed over the decorticated surfaces in the lateral gutters. Postoperative CT scans with reconstructions were reviewed by two independent orthopedic spine surgeons. CT scans of a comparison group of 35 patients who underwent primary single-level posterolateral fusion with ICBG were also reviewed. RESULTS: The overall group had a mean 4.38 CT fusion grade and a 6.6% nonunion rate. Primary one-level fusion cases (n=48) had a mean 4.42 fusion grade a 4.2% nonunion rate. Primary multilevel fusions (n=27) had a mean 4.65 CT grade and no nonunions detected. Assessment of the 35 primary one-level ICBG control cases demonstrated a mean CT grade of 4.35 and a nonunion rate of 11.4%. In the 16 cases of revision for prior nonunion, mean CT grade was 3.81 and 4 subjects had nonunions. Additional subgroup analysis showed that smokers (n=14) had a mean 4.32 CT grade with no nonunions. Men had a mean 4.04 CT grade and an 11.1% nonunion rate compared with a mean 4.61 CT grade and 3.6% nonunion rate in women. This difference was statistically significant (p=.036). No significant differences in fusion rate were observed based upon the specific graft extender used (p=.200). CONCLUSIONS: Posterolateral spine fusion involves a more difficult healing environment with a limited surface for healing, a gap between transverse processes and the milieu of distractive forces. Historically, only ICBG has been able to overcome these challenges and reliably generate a successful posterolateral lumbar spine fusion. In contrast to prior studies, clinically available INFUSE delivers only 12 mg rhBMP-2 at a concentration of 1.5 mg/mL. Despite the lower dose and concentration of rhBMP-2, this study suggests that fusion success with INFUSE is equivalent to ICBG for posterolateral spine fusion. As with ICBG, development of solid fusion or nonunion is a multifactorial process. The use of INFUSE is not a substitute for proper surgical technique or optimization of patient-related risk factors. Additional studies are needed to determine the incremental benefit of a greater rhBMP-2 dose or use of alternative carriers for posterolateral fusion. Finally, correlation between radiographic findings and clinical outcomes, and a cost-benefit analysis are needed. Despite these issues, this study presents compelling evidence that commercially available INFUSE is an effective ICBG substitute for one- and two-level posterolateral instrumented spine fusion.     

Cost-effectiveness of circumferential fusion for lumbar spondylolisthesis: propensity-matched comparison of transforaminal lumbar interbody fusion with anterior-posterior fusion

Background Context

Transforaminal lumbar interbody fusion (TLIF) and dual-approach anteroposterior (AP) are common techniques to achieve circumferential fusion for lumbar spondylolisthesis. It is unclear which approach is more cost-effective.