Oil-soluble vitamins: illegal use for lip augmentation.

Fillers for lip augmentation have become more and more popular in recent years and seem to be indispensable in the cosmetic market nowadays. A series of six young females is presented who developed massive swellings and pain after vitamins A and/or E lip augmentation. The vitamins were extracted from gelatinous capsules (Gericaps [Adipharm EAD, Sofia, Bulgaria], Geritamins [Actavis EAD, Balkanpharma-Dubnitsa AD, Bulgaria], or vitamin E yellow gel capsules) and injected by unprofessional physicians and beauticians in different cosmetic centers. Physical examination revealed firm indurations of the lips and perioral skin, tenderness, erythema, and hard dermal nodules. Histological analysis revealed numerous round-to-ovoid cavities of varying sizes, resulting in a Swiss cheese-like appearance, consistent with lipogranulomas. The patients were treated with systemic and intralesional triamcinolone injections and broad-spectrum antibiotics with good clinical response. In conclusion, these cases demonstrate the danger of the use of unregistered products as fillers injected by unprofessional physicians and beauticians.

Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24.

Founder effect and linkage disequilibrium have been successfully exploited to map single gene disorders, and the study of isolated populations is emerging as a major approach to the investigation of genetically complex diseases. In the search for genetic isolates ranging from Pacific islands to Middle East deserts, the 10 million Gypsies resident in Europe have largely escaped the attention of geneticists. Because of their geographical ubiquity, lack of written history and the presumed social and cultural nature of their isolation, Gypsies are construed as not meeting the criteria for a well defined founder population. Gypsy society has a complex structure with subdivisions and stratifications that are incomprehensible to the surrounding populations. Marginalization by the health care systems in most countries results in a lack of information on causes of morbidity and mortality and little is known about hereditary disorders or the population genetic characteristics of Gypsies. This study is the first example of mapping a disease gene in endogamous Gypsy groups. Using lod score analysis and linkage disequilibrium, we have located a novel demyelinating neuropathy to a narrow interval on chromosome 8q24. We show that the disease, occurring in Gypsy groups of different identity and history of migrations, is caused by a single mutation whose origin predates the divergence of these groups.

External validation of Cardiac disease, Hypertension, and Logarithmic Left anterior descending coronary artery radiation dose (CHyLL) for predicting major adverse cardiac events after lung cancer radiotherapy.

Background and purpose: Major adverse cardiac events(MACE) are prevalent in patients with locally advanced-non-small cell lung cancer(LA-NSCLC) following radiotherapy(RT). The CHyLL model, incorporating coronary heart disease(CHD),Hypertension(HTN),Logarithmic LADV15 was developed and internally-validated to predict MACE among LA-NSCLC patients. We sought to externally validate CHyLL to predict MACE in an independent LA-NSCLC cohort. Patients and methods: Patients with LA-NSCLC treated with RT were included. CHyLL score was calculated:5.51CHD + 1.28HTN + 1.48ln(LADV15 + 1)-1.36CHD*ln(LADV15 + 1). CHyLL performance in predicting MACE was assessed and compared to mean heart dose(MHD) using Cox-proportional hazard(PH) analyses and Harrel's concordance(C)-indices. MACE and overall survival(OS) among low-vs high-risk groups(CHyLL < 5 vs ≥ 5) were compared. Results: In the external validation cohort(N = 102), the median age was 71 years and 55% were females. Most(n = 74,73%), had clinical Stage III disease and 35(34%) underwent surgery. CHyLL demonstrated good MACE prediction with C-index of 0.73(95% Confidence Interval(CI):0.58-0.89), while MHD did not (C-index = 0.46 (95% CI:0.30-0.62)). Per CHyLL, 32(31%) and 70(69%) patients were considered low-and high-risk for MACE, respectively. CHyLL consistently identified lower MACE rates in the low-vs high-risk group(log-rank p = 0.108):0 vs 8%(12 months),5 vs 16%(24 months),5 vs 16%(36 months),and 5 vs 19%(48 months) post-RT. In the pooled internal and external validation cohort(N = 303), MACE rates in low-vs high-risk groups were statistically significantly different(log-rank p = 0.01):1 vs 6%(12 months),3 vs 12%(24 months),6 vs 19%(36 months),and 6 vs 21%(48 months). Conclusions: CHyLL was externally validated and superior to MHD in predicting MACE. CHyLL has the potential to identify high-risk patients who may benefit from cardio-oncology optimization and to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.

Effect of grafted PEG-2000 on the size and permeability of vesicles.

The permeability of PEG-derivatized vesicles produced by the extrusion technique (VETs) to encapsulated D-glucose has been studied. Vesicles were prepared from mixtures of dipalmitoylphosphatidylcholine (DPPC), phosphatidylinositol (PI) and dipalmitoylphosphatidylethanolamine with covalently attached poly(ethylene glycol) of molecular weight 2000 (DPPE-PEG2000). The occurrence of an irreversible temperature-induced size transition of the PEG-derivatized VETs was detected close to the temperature of the main phase transition of the predominant phospholipid component by photon correlation spectroscopy. The permeability of the vesicles towards radioactive D-glucose was studied by a method similar to the one proposed by Johnson and Bangham at 25, 37 and 50 degrees C for VETs with DPPE-PEG content from 0 to 9 mol%. A complex effect of the PEG-coverage was found with a maximum leakage in the range of the transition of the polymer from the mushroom to the brush conformation.

Phospholipid free thin liquid films with grafted poly(ethylene glycol)-2000: formation, interaction forces and phase states.

Free thin liquid films (foam films) formed from aqueous dispersions of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylethanolamine with covalently bound poly-(ethylene glycol) of molecular weight 2000 (DPPE-PEG-2000) were studied by the thin liquid film microinterferometric technique of Scheludko and Exerowa in the temperature range 14-36 degrees C. The surface tension kinetics of the dispersions were studied in order to ensure equilibration of the foam films. These measurements showed that the rate of surface coverage depends slightly on the temperature and does not reach equilibrium values within reasonable time intervals for the dispersions containing only one amphiphile (DPPE-PEG-2000). The destruction of the vesicles at the air/(aqueous dispersion) interface was much faster for the dispersions containing DMPC/DPPE-PEG-2000 mixtures above 23 degrees C, the temperature of the chain-melting phase transition of the main lipid component (DMPC). The dependence of the equilibrium thickness of the foam films on the electrolyte concentration was measured for 1 and 9 mol% DPPE-PEG-2000 at 28 degrees C in the range 10-3 to 0.5 M NaCl. These results indicate that at the low electrolyte concentrations the electrostatic and van der Waals interactions are dominant similar to the foam films stabilized with DMPC alone. At the high electrolyte concentrations the steric repulsion of the PEG layers becomes dominant. The temperature-composition dependence of the bilayer thickness was measured for the foam bilayers at 0.14 M NaCl. The data for the foam bilayer thickness and the comparison with the phase diagrams of PC/PE-PEG dispersions, show that the DMPC/DPPE-PEG-2000 foam bilayers are able to exist in two phase states characterised by different conformations (mushroom and brush) of the grafted polymer.

Novel Ru(III) Complexes with Some Benzothiazole Derivatives: Synthesis, Physicochemical and Pharmacological Investigations.

In this work we present 3 new complexes of Ruthenium (III) with a general formula HL[Ru(L)2Cl4], where L=benzothiazole, 2-methylbenzothiazole and 2-mercaptobenzothiazole. The syntheses were carried out in polar medium under argon. The compounds obtained were characterised by IR-, (1)H-NMR- (13)C-NMR-, UV-VIS-spectroscopy and conductivity measurements. The ligands behaved as monodentate, bounding Ru(III) through the nitrogen atoms from the heterocycle. The cytotoxicity of the new complexes was tested against 2 human leukemic cell lines (K-562 and KE-37), using the MTT-dye reduction assay. The Ru(III) coordination compound with 2-methylbenzothiazole displayed superior activity compared to the other novel complexes. Its IC50 values were comparable to that of the reference cytotoxic drug cisplatin. In general, the ligands displayed only marginal inhibitory effects on the human leukemic cell lines. Moreover, the ability of the complexes to trigger apoptosis was evaluated using a commercially available DNA-fragmentation ELISA kit and the obtained data indicated that their proapoptotic effects well correlate to the MTT-bioassay data.

Hereditary motor and sensory neuropathy--Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries.

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques: postmortem analysis of accuracy, inter-observer agreement, and pitfalls.

INTRODUCTION: Contrast-enhanced magnetic resonance (MR) imaging using ultra small superparamagnetic iron oxide (USPIO) particles is a new noninvasive modality for imaging inflammatory atherosclerotic plaques. We determined the accuracy, interobserver agreement, and potential sources of error of this technique by means of postmortem MR imaging of aortic preparations. MATERIAL AND METHODS: Anesthetized atherosclerotic Watanabe heritable hyperlipidemic (WHHL) rabbits were studied after administration of different dosages of intravenous USPIO (DDM 43/34, IDF Berlin, Germany) and different postcontrast time intervals. A (n = 5) received 0 micromol Fe/kg. B (n = 5) received 50 micromol Fe/kg, 8-hour postcontrast interval. C (n = 5) received 50 micromol, 24 hours. D received 200 micromol, 48 hours. The aortas were removed and 3-mm segments prepared for postmortem examination by MR imaging using a T2-weighted gradient-echo sequence (TR/TE/FA; 41 milliseconds/11 milliseconds/15 degrees ), radiography (mammography), and histology (iron staining). USPIO accumulation was defined as the presence of 20 iron-positive cells per microscopic view (x100 magnification). Two independent readers analyzed the MR images and rated their confidence level for a positive MRI finding, defined as a focal signal loss, on a 5-point scale. The results were evaluated by receiver-operator characteristic (ROC) analysis. RESULTS: Of a total of 621 vessel segments technically acceptable for evaluation, 534 were histologically negative and 87 positive. Accuracy, expressed as the area under the ROC curve, was 0.85 for reader 1 and 0.88 for reader 2. Interobserver agreement was 0.67. False-positive findings were established by at least one reader for 121 of the 621 segments, false-negative findings for only 15 segments. Calcifications and mural thrombi were identified as potential sources of error of the method. CONCLUSION: Postmortem USPIO-enhanced MR imaging of atherosclerotic plaques showed a high accuracy and good interobserver agreement in the animal model used here. Further optimization of the method should aim at reducing the rather high percentage of false-positive results.

A modified method for determination of diffusivities of low molecular substances in non-Newtonian liquids.

A modified method for determination of diffusivities of low molecular substances in non-Newtonian liquids described by the power-law model has been proposed. It is based on the dissolution of Geiss body, with a parameter m=1/3 rotating in an infinite fluid. In this case, the solution of the differential equations of motion and mass transfer is available as an analytical formula for calculating the diffusivity coefficient.The method allows the extension of the variety of media and diffusing species. It has been illustrated with dissolving of gypsum in water and five non-Newtonian liquids. The results obtained have been interpreted taking into account the interaction between calcium ions and polymer molecules of the non-Newtonian system, as well as the heterogeneity of the system near to the dissolving surface.

Quantitative assessment of iron-oxide-enhanced magnetic resonance imaging of the liver: Vessel isointensity is a potential characteristic of liver hemangiomas on late T1-weighted images.

PURPOSE: To test whether a new quantitative measure, the tumor-to-vessel ratio, obtained from late post-iron-oxide-enhanced T1-weighted images allows for differentiating hemangiomas from liver metastases or all malignant liver lesions. MATERIAL AND METHODS: Twenty-six patients (mean 57, range 33-79 years) were prospectively studied at 1.5T magnetic resonance imaging (MRI) with a T1-weighted 2D fast low-angle shot (FLASH) sequence (repetition time/echo time/flip angle; 200 ms/4.8 ms/90 degrees ) and a T2-weighted turbo spin-echo sequence (4072 ms/99 ms/180 degrees ). Imaging was carried out before and at intervals up to 18 min after IV injection of Ferucarbotran (Resovist, Schering, Germany). In 19 patients, one representative malignant lesion was analysed. Eleven hemangiomas were evaluated in 7 patients. Two readers performed a consensus reading with a signal intensity measurement in a lesion, normal liver and hepatic veins, from which ratios were computed. RESULTS: On T1-weighted iron-oxide-enhanced MRI of 30 lesions, tumor-to-vessel signal intensity ratios were distinct in hemangiomas (median 1.04, range 0.99-1.10) as opposed to either metastases (0.64, 0.33-0.77; P < 0.05) or all malignant lesions taken together (0.64, 0.33-0.98; P < 0.05), while the tumor-to-liver ratio was not. CONCLUSION: The tumor-to-vessel ratio may help to differentiate between hemangiomas and metastases. A ratio greater than 0.98 allowed differentiating hemangiomas from metastases with a wide safety margin.

Incontinentia pigmenti: a case associated with cardiovascular anomalies.

Various cutaneous and developmental defects of the eyes, teeth, skeleton, and central nervous system have been detected in infants with incontinentia pigmenti. We report an isolated case of incontinentia pigmenti in a 6-month-old girl in association with tricuspid insufficiency, an abnormal shunt of the right pulmonary vein into the superior vena cava, and pulmonary hypertension. We believe that our findings will help to confirm the association of cardiovascular anomalies in IP.

Thermal transitions in dimyristoylphosphatidylcholine foam bilayers.

Thermal transitions in the system dimyristoylphosphatidylcholine/water/ethanol/sodium chloride were studied in the temperature range 10-31 degrees C. The water-ethanol dispersions were investigated by differential scanning calorimetry and the foam bilayers by the microinterferometric method for investigation of thin liquid films. Calorimetry showed that an increase in ethanol content (up to 47.5 vol.%-the concentration used in the experiments with foam bilayers) did not significantly influence the temperature of the main phase transition and led to the disappearance of the pretransition. The microinterferometric study of the foam bilayer thickness showed that there were two thermal transitions-at 13 and 23 degrees C. An Arrhenius type dependence was obtained for the critical concentration of dimyristoylphosphatidyl-choline (DMPC) in the solution, which was necessary for the formation of the foam bilayer. A steep change in the slope of the linearized Arrhenius dependence was found at 23 degrees C. Values of the binding energy of a DMPC molecule in the foam bilayers were calculated using the hole-nucleation theory of stability and permeability of bilayers. It was proved that the phase transition at 23 degrees C was due to melting of the hydrocarbon tails of phospholipid molecules. The low-temperature phase transition was assumed to be due to a change in the tilt of the hydrocarbon tails. These experiments demonstrate for the first time the occurrence of phase transitions in foam bilayers.

Preparation, physicochemical characterization and pharmacological study of novel ruthenium(III) complexes with imidazole and benzimidazole derivatives.

Complex compounds of ruthenium(III) with 1,2-dimethylimidazole (CAS 1739-84-0), 2-phenylimidazole (CAS 670-96-2) and 2-aminobenzimidazole (CAS 934-32-7) were prepared and were characterised by physicochemical methods. Coordination sites were determined. The complexes were tested for cytotoxic activity using MTT (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye-reduction assay and the values LD50 were evaluated.

Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings.

A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait disorder followed by upper limb weakness in the second decade and, in most subjects, by deafness which is most often first noticed in the third decade. Sensory loss affecting all modalities is present, both this and the motor involvement predominating distally in the limbs. Skeletal deformity, particularly foot deformity, is frequent. Severely reduced motor nerve conduction velocity indicates a demyelinating basis, which was confirmed by nerve biopsy. The three younger patients biopsied showed a hypertrophic 'onion bulb' neuropathy. The hypertrophic changes were not evident in the oldest individual biopsied and it is likely that they had regressed secondarily to axon loss. In the eight cases in which brainstem auditory evoked potentials could be recorded, the results suggested demyelination in the eighth cranial nerve and also abnormal conduction in the central auditory pathways in the brainstem. As no myelin genes are known to be located at chromosome 8q24, the disorder may involve a gene for a novel myelin protein or be due to an abnormality of axon-Schwann cell signalling.