Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI-TOF/MS.

OBJECTIVE: This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. MATERIALS AND METHODS: Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO-RAD Data Manager(™) (Version 3.5). RESULTS: We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA. CONCLUSION: Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Brain MRI white matter lesions in migraine patients: is there a relationship with antiphospholipid antibodies and coagulation parameters?

Brain magnetic resonance imaging (MRI) studies in migraine patients have demonstrated lesions consisting of focal regions of increased signal intensity within the white matter. Antiphospholipid antibodies are known to have a role in many diseases including migraine. The aim of the present study was to ascertain the relationship between MRI-visualized cerebral focal hyperintense lesions and serum antiphospholipid antibody levels, as well as blood coagulation parameters in migraine patients. One hundred and two (77 females, 25 males, mean age 33.8 +/- 11.1) consecutive migraine patients and a control group of 94 (70 females, 24 males, mean age 33.2 +/- 10.8) healthy subjects were enrolled. All individuals underwent brain MRI. Complete blood examinations, autoantibodies, antiphospholipids antibodies including anticardiolipin and lupus anticoagulant (aCL, LAC), antithrombin III, Protein C and S serum levels were ascertained in the subjects who presented white matter lesions on MRI. Twenty-seven (26.4%) migraine patients and six (6.3%) healthy subjects in the control group showed focal regions of increased intensity signal within cerebral white matter (odds ratio 5.3, 95% CI: 1.98-16.36). In migraine patients with white matter lesions, antiphospholipid antibodies were not detected and serum levels of antithrombin III, and proteins C and S were normal. White matter lesions in migraine patients are fairly common. This finding is not associated with antiphospholipid antibodies or abnormal coagulation parameters. The significance of such lesions at present remains unclear.

Spectroscopic, diffusion and perfusion magnetic resonance imaging at 3.0 Tesla in the delineation of glioblastomas: preliminary results.

Recent advances in magnetic resonance imaging (MRI) have allowed the evaluation of metabolic, diffusion and hemodynamic features of malignant gliomas. The aim of this study was to evaluate whether such information provided useful, complementary information to conventional MRI for improving the evaluation of glioblastoma extent. Ten patients with glioblastoma multiforme underwent conventional MRI, proton MR spectroscopic imaging (1H-MRSI), perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Metabolite signals, including normalized choline, N-acetylaspartate, creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. In edematous-appearing areas, 3 multiparametric patterns were identified: infiltrating tumor, with abnormal metabolite ratios, lower ADC and higher rCBV; pure edema, with normal metabolite ratios, higher ADC and lower rCBV; and tumor-infiltrated edema, with abnormal metabolite ratios and intermediate ADC and rCBV. In normal-appearing areas, 2 multiparametric patterns were identified: tumor-infiltrated tissue, with abnormal metabolite ratios and higher rCBV; and normal tissue, with normal MR parameters. The combination of 1H-MRSI, DWI and PWI features contributed to delineation of glioblastomas, offering information not available with conventional MRI. This approach may enhance the assessment of brain gliomas, providing useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Supratentorial low-grade gliomas. Neuroradiology.

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumors is magnetic resonance imaging. A brain tumors can be reliably ruled out, if the standard magnetic resonance examination is performed properly and experts interpret the results as negative for tumor. In this paper we will illustrate morphological aspects of low-grade supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low-grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell astrocytoma). Then the main practical applications of functional imaging in neurosurgery will be also debated.

Sinus Lift Augmentation by Using Calcium Sulphate. A Retrospective 12 Months Radiographic Evaluation Over 25 Treated Italian Patients.

PURPOSE: The aim of this investigation was to assess bone healing of sinus lift procedure in which the augmentation has been performed by using calcium sulphate like bone substitutes. The methods of this investigation how the use of Cone Beam Computed Tomography (CBCT) may be a valid instrument to support reconstructive surgery of the jaws. PATIENTS AND METHODOLOGY: 25 Patients presented large bone defects after tooth extractions located in the upper jaw posterior area. Vertical bone volume was assessed by CBCT examinations before and about six months after sinus lift surgery. RESULTS: Examined defects treated with sinus lift surgery and evaluated by CBCT showed a strong increasing on the bone volume at 6 months follow up control. CONCLUSION: Calcium sulphate application in sinus lift surgery represent a safe and predictable option in the place of autologous bone. Therefore the application of CBCT investigation may give the clinicians the opportunity of evaluating with high precision value, the consistence of the bone defects before the surgery.

Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients.

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

MR angiography in carotid stenosis: a comparison of three techniques.

PURPOSE: To compare the accuracy of three different magnetic resonance angiography (MRA) techniques for studying steno-occlusive disease of carotid arteries. METHODS: 64 patients were evaluated with three MRA techniques- three-dimensional (3D) time-of-flight (TOF), two-dimensional (2D) TOF, and 3D Phase-Contrast (PC); the acquisition was in the axial plane, the volume included the carotid bifurcation. Digital subtraction angiography (DSA) was considered the 'gold standard'. The MRA images were reprojected with a maximum intensity pixel ray-tracing (MIP) algorithm. The three MRA techniques were blindly graded as normal, mildly stenotic (0-29%), moderately stenotic (30-49%), severely stenotic (70-99%), or occluded. RESULTS: DSA provided 128 diagnostic judgments: 92 were negatives and 36 positives. 2D TOF was in agreement with angiography in 116 of 128 cases (90%), but overestimated the results in seven cases and underestimated in five cases. 3D TOF agreed with angiography in 125 of 128 cases (97%), with one overestimation and two under estimations. 3D PC was concordant in 116 of 128 cases (90%), overestimating in six cases, underestimating in six cases. The sensitivity, specificity and diagnostic accuracy for 2D TOF was, respectively 84%, 94%, and 92%, while for 3D TOF was 94%, 100%, and 98%, and for 3D PC 86%, 98%, and 95%. The comparison of the three different MRA techniques provided no statistically significant difference (Friedman test P < 0.05). CONCLUSION: The high degree of diagnostic accuracy of MRA found in the study of the steno-occlusive disease of the carotid arteries confirms the high degree of reliability of this methodology carried out with the 3D TOF technique, compared to 2D TOF and 3D PC.

High-field proton MRS of human brain.

Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing 1H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, gamma-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field 1H-MRS would expand the application in the fields of clinical research and diagnostic routine.

Contrast-enhanced MR angiography (CE MRA) in the study of the carotid stenosis: comparison with digital subtraction angiography (DSA).

PURPOSE: To determine sensitivity, specificity and diagnostic accuracy of contrast-enhanced magnetic resonance angiography (CE MRA) compared to digital subtraction angiography (DSA) in the study of carotid stenosis. METHODS AND MATERIAL: We studied 23 patients with suspected cerebro-vascular insufficiency by carotid stenosis. Diagnostic examinations by means of CE MRA and DSA were carried out within 24 hours of each other. A 1.5 T superconductive magnet (Signa-General Electric) was used for CE MRA. This technique was performed using a fast spoiled gradient echo recalled (SPGR) sequence acquired in coronal plane 13 sec after injection of contrast medium. Imaging parameters were: TR/TE/FA 8 msec/1 msec/60 degrees, matrix 256 x 128, 1 excitation, FOV 18 x 13 cm, 28 slices per slab, slice thickness of 1 mm, acquisition time of 32 sec. The post-processing was performed using maximum intensity projection (MIP) and targeted MIP. For DSA examinations a Politron 1000 VR unit (Siemens) was used. RESULTS: In the identification and quantification of lesions, CE MRA showed values of 100%. In particular, in comparison to DSA, CE MRA was accurate in diagnosing all true negative and positive cases. The location of stenosis evaluated with CE MRA agreed in all cases with DSA. CONCLUSION: In our experience CE MRA proved to be a very valuable technique in diagnosing carotid stenosis, showing the same diagnostic accuracy as DSA. In this way CE MRA appears to be a substantial alternative technique to conventional MRA and other non-invasive diagnostic methods.

Long-term in vitro precision of single slice peripheral Quantitative Computed Tomography (pQCT): multicenter comparison.

In a multicenter evaluation the precision and stability of single slice peripheral Quantitative Computed Tomography (pQCT) systems were assessed. Compared to central Europe the peripheral QCT device is also widely used in the Italian health care system. Phantoms were measured frequently on each machine in four pQCT scanners over a two-year period using an identical automated software program. Intrasite and intersite phantom mineral densities, expressed in units of mg/cm3, were analyzed and examined. The short and long term precision were estimated from the consistency of these measurements using the root mean square error and expressed as coefficient of variation in percent (% CV). Short term precision was good (mean intrasite coefficient of variation (CV) 0.21 +/- 0.056 standard deviation (SD)). Intersite measurements of a single phantom revealed differences between machines of the same type of not more than 2.9 mg/cm3. At four sites frequent phantom measurements revealed a mean CV of 0.18% (range 0.12-0.28). No significant changes in the regression slopes (drift of the machine versus time) were observed. We conclude that the in vitro precision and stability of the single slice pQCT systems are sufficiently high and unlikely to negatively affect the in vivo precision.

[Rupture of hydatid cyst with invasion of the bile ducts and acute pancreatitis]. / Invasione delle vie biliari da rottura di cisti idatidea e pancreatite acuta.

Acute pancreatitis is a rare complication of intrabiliary rupture of an hydatid cyst. The Authors report a new case and discuss its clinical, radiological and surgical findings with special emphasis to the diagnostic approach and surgical management.

SPECT analysis of a new implant surface: a human preliminary report.

AIM: Several recent medical reports have focused attention on the possible application of skeletal scintigraphy imaging in odontostomatology. The aim of the present report was to assess the influence of a new implant surface on peri-implant osteoblastic activity through bone scintigraphy. METHODS: Implants were placed in one healthy subject. A nuclear medicine investigation with single-photon emission-computed tomography (SPECT) was performed at 30 and 90 days after implant placement. The study was completed with acquisition of planar images of the skull in an anterior view and the use of regions of interest (ROIs) of the same size in the area corresponding to new surfaces implants and in the opposite maxilla (at the control sites). Count density ratios (counts/pixel) obtained from each ROI were used for a quantitative/relative assessment. Tomographic images were evaluated with a qualitative method. RESULTS: Routine planar methodology provided a direct measure of cellular activity of the examined areas. The difference in count density ratio registered from the same ROI between the first and the second scintigraphy revealed the course of peri-implant osteoblastic activity, which was very high in the first month and then declined during subsequent months. CONCLUSIONS: In spite of the small number of involved patients, the results obtained from this pilot study suggest that nuclear medicine investigation held advantages in oral implantology to clarify those aspects still unknown dealing with osteoblastic activity.

Role of advanced MR imaging modalities in diagnosing cerebral gliomas.

The objective of this study was to evaluate the potential role of newly developed, advanced magnetic resonance (MR) imaging techniques (spectroscopy, diffusion and perfusion imaging) in diagnosing brain gliomas, with special reference to histological typing and grading, treatment planning and posttreatment follow-up. Conventional MR imaging enables the detection and localisation of neoplastic lesions, as well as providing, in typical cases, some indication about their nature. However, it has limited sensitivity and specificity in evaluating histological type and grade, delineating margins and differentiating oedema, tumour and treatment side-effects. These limitations can be overcome by supplementing the morphological data obtained with conventional MR imaging with the metabolic, structural and perfusional information provided by new MR techniques that are increasingly becoming an integral part of routine MR studies. Incorporation of such new MR techniques can lead to more comprehensive and precise diagnoses that can better assist surgeons in determining prognosis and planning treatment strategies. In addition, the recent development of new, more effective, treatments for cerebral glioma strongly relies on morphofunctional MR imaging with its ability to provide a biological interpretation of these characteristically heterogeneous tumours.

Phenylketonuria: white-matter changes assessed by 3.0-T magnetic resonance (MR) imaging, MR spectroscopy and MR diffusion.

PURPOSE: This study evaluated the sensitivity of a 3.0-Tesla (T) magnetic resonance imaging (MRI) in measuring cerebral phenylalanine using proton magnetic resonance spectroscopy and in assessing MR-documented white-matter changes by means of diffusion studies (diffusion-weighted imaging, apparent diffusion coefficient map; diffusion tensor imaging) in patients with phenylketonuria. MATERIALS AND METHODS: Thirty-two patients with the classical clinical and biochemical deficits of phenylketonuria underwent biochemical (blood phenylalanine), genotypic (phenylalanine hydroxylase gene) and radiological investigation by means of MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging with a 3.0-T scanner. RESULTS: Periventricular and subcortical white-matter changes were detected on all MR scans. In 29/32 patients, proton magnetic resonance spectroscopy easily documented abnormal signal elevation at 7.36 ppm, corresponding to phenylalanine, despite its low concentration. Phenylalanine signal amplitude relative to the creatine/phosphocreatine signal increased linearly with blood phenylalanine values (r 0.7067; p<0.001). Diffusion MRI demonstrated hyperintensity in the areas exhibiting MRI changes as well as decreased apparent diffusion coefficient values, but fractional anisotropy indices were normal. CONCLUSIONS: The high signal, together with better spectral, spatial, contrast and temporal resolution, makes the 3.0-T MR the most suitable technique in the study of the phenylketonuria. In particular, the multimodal approach with MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging can provide more information than previous studies performed with low-field systems.