Surface properties of nanocrystalline TiO2 coatings in relation to the in vitro plasma protein adsorption.

This study reports on the selective adsorption of whole plasma proteins on hydrothermally (HT) grown TiO2-anatase coatings and its dependence on the three main surface properties: surface charge, wettability and roughness. The influence of the photo-activation of TiO2 by UV irradiation was also evaluated. Even though the protein adhesion onto Ti-based substrates was only moderate, better adsorption of any protein (at pH = 7.4) occurred for the most negatively charged and hydrophobic substrate (Ti non-treated) and for the most nanorough and hydrophilic surface (HT Ti3), indicating that the mutual action of the surface characteristics is responsible for the attraction and adhesion of the proteins. The HT coatings showed a higher adsorption of certain proteins (albumin 'passivation' layer, apolipoproteins, vitamin D-binding protein, ceruloplasmin, α-2-HS-glycoprotein) and higher ratios of albumin to fibrinogen and albumin to immunoglobulin γ-chains. The UV pre-irradiation affected the surface properties and strongly reduced the adsorption of the proteins. These results provide in-depth knowledge about the characterization of nanocrystalline TiO2 coatings for body implants and provide a basis for future studies on the hemocompatibility and biocompatibility of such surfaces.

Epstein-Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

The ubiquitous Epstein-Barr virus (EBV) is related to the development of several lymphoid and epithelial malignancies and is also the aetiological agent for infectious mononucleosis (IM). BZLF1, an immediate early gene, plays a key role in modulating the switch from latency to lytic replication, hence enabling viral propagation. Polymorphic variations in the coded protein have been studied in other geographical regions in a search for viral factors that are inherent to malignancies and differ from those present in benign infections. In the present study, in samples of paediatric patients with benign IM and paediatric patients with malignant lymphomas, we detected previously described sequence variations as well as distinctive sequence polymorphisms from our region. By means of phylogenetic reconstruction, we characterized new phylogenetically distinct variants. Moreover, we described an association between specific variants and the studied pathologies in our region, particularly variant BZLF1-A2 with lymphomas and BZLF1-C with IM. Additionally, length polymorphisms within intron 1 were also assessed and compared between pathologies resulting in an association between 29-bp repeated units and lymphomas. In conclusion, this is the first report to characterize BZLF1 gene polymorphisms in paediatric patients from our geographical region and to suggest the association of these polymorphisms with malignant lymphomas.

Epstein Barr virus in relation to apoptosis markers and patients' outcome in pediatric B-cell non-Hodgkin lymphoma.

In this study, we investigated Epstein Barr virus (EBV) presence, associated to proliferation and apoptosis proteins in pediatric B-cell Non-Hodgkin lymphoma (B-NHL). EBERs, Ki67, active caspase 3, Bax and Bcl2 were analyzed on B-NHL tissue from 40 patients. Forty percent showed EBV expression, significantly higher among patients ⩽10years (P=0.027), and associated with immunosuppression (P=0.020), but not associated apotosis markers. However, EBV was associated with a worse event-free survival (P=0.016), particularly under immunosuppression. Even though EBV did not seem to alter apoptotic pathways, it exhibited survival disadvantage and could be an important cofactor in B-cell lymphomagenesis in younger children.

Lumbar arachnoiditis and thecaloscopy: brief review and proposed treatment algorithm.

The term arachnoiditis describes the inflammation of the meninges and subarachnoid spaces. Lumbar arachnoiditis is characterized by obliterated nerve root sleeves and the adherence of nerve roots to each other in the proximity of the cauda equina, and may be secondary to infectious diseases or tumors, iatrogenic (subsequent to spinal surgery) or idiopathic. It is not very clearly defined epidemiologically or clinically, and various theories regarding its pathophysiology have been proposed; furthermore, its treatment is difficult because there is a lack of evidence-based diagnostic and therapeutic gold standards. Thecaloscopy has been recently described as a novel technique for retrograde transcutaneous neuroendoscopic inspection of the subarachnoid structures of the lumbar thecal sac; it has also been suggested for the treatment of lumbar arachnoiditis. We here review the most modern techniques for the treatment of this disease such as thecaloscopy and neurostimulation.

The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors.

In geometrical terms, tumor vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic, together with the highly variable vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological features have now been well established, quantitative analyses of neovascularity in two-dimensional histological sections still fail to view tumor architecture in non-Euclidean terms, and this leads to errors in visually interpreting the same tumor, and discordant results from different laboratories. A review of the literature concerning the application of microvessel density (MVD) estimates, an Euclidean-based approach used to quantify vascularity in normal and neoplastic pituitary tissues, revealed some disagreements in the results and led us to discuss the limitations of the Euclidean quantification of vascularity. Consequently, we introduced fractal geometry as a better means of quantifying the microvasculature of normal pituitary glands and pituitary adenomas, and found that the use of the surface fractal dimension is more appropriate than MVD for analysing the vascular network of both. We propose extending the application of this model to the analysis of the angiogenesis and angioarchitecture of brain tumors.

Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation.

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein-Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

Expression of cannabinoid receptors and neurotrophins in human gliomas.

Recent studies have shown an anti-tumour activity of cannabinoid receptors CB1 and CB2 in gliomas. This effect was mediated by neurotrophins in breast and prostate carcinoma, while in gliomas this relationship has not yet been considered. The aim of this study was to investigate the expression of cannabinoid receptors CB1 and CB2, neurotrophin NGF and NT-3 and their receptors TrkA and TrkC in glioma and endothelial cells. The analysis was performed in 14 gliomas and 2 non-tumour brain specimens by immunohistochemistry and real-time quantitative-polymerase chain reaction (RTQ-PCR). Gliomas showed a weak immunoreactivity for CB1 and CB2 in tumour and in endothelial cells, and for NGF/TrkA mainly in tumour cells, while a moderate/diffuse immunoreactivity was found for NT-3/TrkC. CB2 was expressed on 3 out of 6 low-grade gliomas and in all high-grade gliomas. Non-tumour brain tissues were weakly positive in astrocytes and endothelium for CB1, CB2, NT-3 and TrkC and negative for NGF and TrkA. By RTQ-PCR, gliomas showed low mRNA levels of NGF/TrkA and moderate levels of CB1, NT-3 and TrkC. CB2 mRNA expression was low or absent. A potential role of cannabinoids, particularly of CB2 agonists devoid of psychotropic side effects, in glioma therapy could have a basis in glioblastomas, because they were all positive, though weakly, to CB2. The presence of neurotrophins and their receptors, mainly NT-3 and TrkC, suggests a possible role of these pathways in glioma growth/invasion, but further investigations are required to verify this hypothesis and a potential relationship between cannabinoids and neurotrophins.

Management of prosthetic abutments respecting peri-implant soft tissues.

Periodontal and peri-implant soft tissues are very similar in many aspects (phenotype, mucosal dimensions, biological width). In peri-implant tissue, the mucosal seal is localized apically to the gap existing between the fixture and the prosthetic abutment. This is due to mechanical trauma created by screwing and unscrewing the prosthetic components, to mechanical deformation produced under functional stress and to bacterial colonization. To reduce the effects of this gap on peri-implant soft tissues stability several options are available: supracresta fixture positioning, reduction of the fixture-abutment gap, and minimizing the prosthetic steps. A clinical case was illustrated. Abutments (Gingi-hue 3I with a fixture-abutment gap less than 2 mm and a fixture abutment angle rotation of 0.4 degrees ) were screwed on the fixtures after the second stage surgery and used as impression transfer. These abutments were prepared in the laboratory and definitively screwed after the impression session. The use of definitive abutments as transfer reduces the session number and allows the peri-implant soft tissues to heal without beeing troubled by screwing and unscrewing of the prosthetic components.

A diagnosis of left ventricular hypertrophy on ECG is associated with a high cardiovascular risk: findings from a 40- to 69-year-old cohort in general practice.

OBJECTIVE: Left ventricular hypertrophy (LVH) is an independent cardiovascular (CV) risk factor in both sexes. We studied if a diagnosis of LVH on electrocardiogram (ECG) was associated with a 'high CV risk condition' among 40- to 69-year-old individuals cared for by GPs. METHODS: We studied 4250 individuals, 5.4% of whom had LVH. Cross-sectional frequencies, and age- and gender-adjusted statistical differences have been calculated. RESULTS: All the study variables were significantly worse for 'LVH' than 'non-LVH' individuals (except smoking). The 'LVH' had both a mean '5-year CV risk' significantly greater than 'non-LVH' individuals (27.0% versus 8.6%), and a significantly higher prevalence of a '5-year CV risk >15%' (89% versus 15%). CONCLUSIONS: A diagnosis of LVH on ECG among the adult individuals of an opportunistic cohort from general practice was associated with a 6-fold greater prevalence of a 'high CV risk condition'.

Sinus floor augmentation with autogenous iliac bone block grafts: a histological and histomorphometrical report on the two-step surgical technique.

In thirteen patients, screw-type endosseous implants were inserted 6 months after sinus floor elevation and augmentation with autogenous iliac bone block grafts. Bone biopsies were harvested at graft positioning (baseline), at implant placement (6 month) and at abutment connection (1 year). Histological evaluation suggested a decrease in the volume of mineralized tissue and in the vitality of the grafts 6 months after graft insertion, followed by an increase at abutment connection. Histomorphometric analysis of the bone specimens showed that, at implant placement, bone content was reduced by 5.2% on average, while 12 months after grafting it had increased by 4.8% compared to the amount of mineralized tissue contained in the graft at baseline. The results suggest that in sinus floor augmentation procedures with autogenous iliac bone blocks, a two-step surgical technique allows implant insertion when graft healing is entering a phase of greater density and vitality.

Seckel's syndrome and malformations of cortical development: report of three new cases and review of the literature.

Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar facial appearance. In the past, this condition was overdiagnosed, and most attention was given to the facial and skeletal features to define more precise diagnostic criteria. The presence of mental retardation and neurologic signs is one of the peculiar features of this syndrome, but only recently were rare cases of malformation of cortical development described, as documented by magnetic resonance imaging (MRI). Here, we present three new cases of Seckel's syndrome showing different malformations of cortical development (one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one bilateral opercular macrogyria). We hypothesize that the different types of clinical expression of our patients could be explained by different malformation of cortical development types. We think that MRI studies could be performed in malformative syndromes because of the possible correlations between type and extent of the lesion and the clinical picture of any individual case.

A clinical spectrum of the myoclonic manifestations associated with typical absences in childhood absence epilepsy. A video-polygraphic study.

We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE), presenting with typical absence seizures associated with myoclonic manifestations of the face or neck. All patients underwent repeated and prolonged split-screen video-polygraphic EEG recordings. The polygraphic recordings and clinical correlations of the absence seizures were analysed. All patients presented with multi-quotidian, typical absence seizures. During the absences, the patients could show mild, rhythmic, myoclonic jerks involving facial areas (eyebrows, nostrils, perioral region, chin) or neck muscles (sternocleidomastoideus), with the same frequency as the spike-wave complexes. Polygraphic tracings demonstrated that the myoclonias were correlated to the spike component. Clinically, all patients showed a benign course, with complete seizure control under antiepileptic treatment. In the follow-up, 7 patients withdrew from treatment without relapse. We conclude that all our patients showed an electroclinical picture consistent with CAE. The occurrence of myoclonic manifestations of the face or neck associated with the absences did not influence the benign course of their disease. The electroclinical features observed in our group of patients differentiates our cases both from epilepsy with myoclonic absences and from absences with perioral myoclonia (with Video).

Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease.

It is often difficult to assess small bowel recovery in adults with coeliac disease on a gluten-free diet (GFD). This prospective study compares changes in intestinal permeability with changes in intestinal biopsy at various intervals after commencing a GFD. Intestinal permeability was measured by lactulose/rhamnose absorption from 1 week to 24 months after commencing a GFD. Intestinal morphometry was measured by villus area, crypt length and mitotic count per crypt at diagnosis and after commencing a GFD. Median intestinal permeability values decreased from 0.47 (n = 35) at diagnosis to 0.25 (n = 17) after 1 week and to 0.16 (n = 18) after 2 months of a GFD. Rhamnose absorption improved significantly at an early stage, from 6.6% (untreated) to 15.4% at 3 months of a GFD, whereas the decrease in lactulose permeation took longer: from 3.4% (untreated) to 0.8% after 12 months of a GFD. Mean villus area (n = 29) was reduced to 16% of control values at diagnosis, and improved to a maximum of 48% after 6 months on a GFD, but did not change thereafter. Mean crypt length and mitotic count per crypt were increased by 222% and 356% respectively at diagnosis, and these parameters remained elevated at 172% and 216% above control values after 6 months of a GFD. We conclude that intestinal permeability improves within 2 months after starting a GFD, but that measurable intestinal biopsy improvement requires ingestion of a GFD for at least 3-6 months, and even then remains incomplete.

[Care recommendations for type 1 neurofibromatosis]. / Raccomandazioni assistenziali per la neurofibromatosi tipo 1.

Neurofibromatosis type 1 (NF1) is a progressive, multisystem disorder affecting about 1:3000 individuals. About one third of patients show serious complications and about one half are mildly affected. Since the original National Institutes of Health Consensus Conference in 1987, that established the clinical criteria for the diagnosis of NF1, there has been significant progress toward a more complete understanding of the molecular bases for NF1, and our knowledge of the natural history and management of the NF1 has significantly improved. Despite these advances, the diagnosis of NF1 is still based largely on clinical criteria and no individual prognostic evaluation or definitive medical therapy are available. The recommendations for the care of NF1 patients and their families are constantly changing: according to the new guidelines, the mainstay of management is anticipatory guidance and surveillance for treatable complications; surveillance usually includes annual follow-up visits, unless symptoms call for more frequent visits or more accurate diagnostic evaluation.

Effect of one year residence in Antarctica on bone mineral metabolism and body composition.

OBJECTIVE: To evaluate the changes of the biochemical parameters of mineral metabolism and to assess the effect of these changes on the bone mass of young healthy men who voluntarily lived in the Antarctic Continent for one year. DESIGN: Lumbar spine and whole body bone mineral density (BMD) were measured pre- and post-campaign (14 months later). Serum and urinary biochemical parameters were measured every two months. Serum levels of calcium, phosphate, total alkaline phosphatase, parathormone (PTH) and 25-hydroxyvitamin D (250HD) were determined in blood fasting samples; and hydroxyproline, calcium and creatinine in 2 h fasting urine. The subjects received a dose of 100 i.u./d of vitamin D during May after obtaining the samples and then an average of 125 i.u./d from July to January. SUBJECTS: Seventeen healthy volunteers, who left Buenos Aires during the 1992 summer: ten arrived in the Belgrano II Base at the end of January and the other seven arrived in San Martín in March and stayed there up to summer 1993. RESULTS: BMD increased in lumbar spine (L2-L4), total body and the subarea of the legs but there were no differences between the pre- and post-campaign values in arms and pelvis. The percentage of fat mass decreased significantly after 1 y of residence in Antarctica, in comparison to the basal values. Most biochemical parameters remained unaltered and within the normal range during the whole study. PTH showed a nadir in March (end of the summer) when compared to initial levels (73.0 +/- 28.2 vs 39.9 +/- 32.7 pg/ml, P < 0.05), and recovered its initial value in spring. Calcium levels showed a significant decrease in March (9.5 +/- 0.4 vs 8.5 +/- 1.0 mg%, P < 0.01). 25OHD levels began to decrease in March (24.7 +/- 6.4 vs 18.7 +/- 5.3 ng/ml), reaching a minimum value whose difference approached statistical significance during the winter period (July: 16.4 +/- 8.2 ml, 0.05 < P < 0.06). No significant changes in serum phosphate, total alkaline phosphatase, urinary hydroxyproline/creatinine and calcium/creatinine ratios were found through the year. CONCLUSIONS: 25OHD levels decreased in autumn and winter (nadir in July) and recovered the initial levels by the end of the campaign. An unexplained marked diminution in PTH and serum calcium was found at the beginning of the campaign. In spite of the low vitamin D levels, bone mass in this group of young healthy men increased, probably because of their intense physical activity.

The biguanide compound metformin prevents desensitization of human pancreatic islets induced by high glucose.

Pancreatic islet desensitization by high glucose concentrations is a temporary and reversible state of beta-cell refractoriness to glucose (and possibly other secretagogues), due to repeated or prolonged pre-exposure to increased glucose concentrations. We evaluated whether the oral antidiabetic agent metformin affects this phenomenon in isolated, human pancreatic islets, and whether the possible effects of the biguanide are influenced by the presence of a sulphonylurea, glyburide. Islets prepared from five human pancreases were incubated for 24 h in M199 culture medium containing either 5.5 or 22.2 mmol/l glucose, with or without a therapeutic concentration (2.4 microg/ml) of metformin. Then, the islets were challenged with either 3.3 mmol/l glucose, 16.7 mmol/l glucose, or 3.3 mmol/l glucose + 10 mmol/l arginine, and insulin release was measured. After incubation in the absence of metformin, the human islets exposed to 22.2 mmol/l glucose showed no significant increase in insulin release when challenged with 16.7 mmol/l glucose (confirming that hyperglycemia desensitizes pancreatic beta-cells). In the presence of metformin, the islets fully maintained the ability to significantly increase their insulin release in response to glucose, even when previously exposed to 22.2 mmol/l glucose. No major effect on arginine-induced insulin release was observed, whatever the culture conditions. The protective action of metformin was observed also when glyburide was present in the incubation medium, whereas the sulphonylurea alone did not affect insulin release from the islets previously exposed to high glucose concentrations. These in vitro results suggest that metformin can prevent the desensitization of human pancreatic islets induced by prolonged exposure to increased glucose concentrations.

Mandibular implant-retained overdenture: a clinical trial of two anchorage systems.

This in-vivo study aimed to investigate the load on the working-side implant and on the edentulous distal mucosa of the nonworking side in a mandibular implant-retained overdenture (MIR-OVD) anchored to 2 implants by either a ball- or a clips-and-bar attachment. Three female patients were provided with duplicate dentures anchored in the 2 ways. Strain on the implant was investigated using a strain-gauged abutment, and load on the mucosa was measured using a suitably placed load cell. Ball attachments appeared to provide greater stability to the MIR-OVD, since load was more evenly distributed onto the distal mucosa of both sides. When the MIR-OVD was bar-anchored, axial load on the working-side abutment increased.