MR Imaging Findings of Iron Overload

Hemochromatosis can be classified as (a) primary, when it originates from a genetic disturbance that promotes the increase of iron absorption, or (b) secondary, when it relates to chronic diseases or to multiple transfusions. The distribution of iron accumulation differs between these two forms; therefore, they can be distinguished by using imaging methods in the majority of cases. Magnetic resonance (MR) imaging is the most sensitive and specific imaging modality in the diagnosis of hemochromatosis. The susceptibility effect caused by the accumulation of iron leads to signal loss in the affected tissues, particularly with the T2*-weighted sequences, which makes the diagnosis of iron overload possible. By using MR imaging techniques, it is possible to estimate the hepatic iron concentration in a noninvasive way, thereby avoiding repeated biopsies. Hemochromatosis can lead to complications, such as a higher frequency of neoplasia, particularly the development of hepatocellular carcinoma. Other neoplasms, such as colorectal tumors, are also associated. Complications related to the treatment of chronic anemia include the appearance of peliosis hepatis and tumors, which can regress after the suspension of treatment with drugs. Knowledge of the disease and of the patterns of iron deposition in patients with iron overload enables not only diagnosis, but also treatment, follow-up, and the detection of possible complications by using imaging methods. (C) RSNA, 2009 . radiographics.rsna.org

The role of micro-anchor devices in medial canthopexy

Telecanthus, the lateral displacement of the medial canthus, can be a congenital deformity or can occur after facial trauma or tumor resection. Treatment of telecanthus remains a challenge for plastic surgeons. For proper correction, it is necessary to shift the medial canthus medially, fixing its tendon to the bone. The ideal technique would allow easy, safe, and stable fixation of the tendon, permit a unilateral approach with minimal incisions, and be cost-effective. The purpose of this study was to evaluate the feasibility and results (immediate and long-term) of medial telecanthus repair using ipsilateral titanium microanchor fixation. Nine patients, 7 with unilateral telecanthus and 2 with bilateral telecanthus, underwent ipsilateral canthopexy involving a microanchor device. Anthropometric measurements of the orbital regions were taken before, immediately after, and at 1 year after surgery. Data for the affected sides were compared with those for the unaffected sides, and the evolution of those values was assessed throughout the 1-year follow-up period. For all patients, the final values were lower than those initially obtained. At 1 year after surgery, the intercanthal distance was reduced to age-adjusted normal values in all cases. On the operated side, stable improvement was observed in terms of the distance from the medial canthus to the midline, although some degree of recurrence was noted in most of the patients. The use of a microanchor system for medial canthopexy can be considered an easily performed and effective option for treating canthal dystopia, especially when an ipsilateral approach is preferred.

Protein disulfide isomerase redox-dependent association with p47(phox): evidence for an organizer role in leukocyte NADPH oxidase activation

Mechanisms of leukocyte NADPH oxidase regulation remain actively investigated. We showed previously that vascular and macrophage oxidase complexes are regulated by the associated redox chaperone PDI. Here, we investigated the occurrence and possible underlying mechanisms of PDI-mediated regulation of neutrophil NADPH oxidase. In a semirecombinant cell-free system, PDI inhibitors scrRNase (100 mu g/mL) or bacitracin (1 mM) near totally suppressed superoxide generation. Exogenously incubated, oxidized PDI increased (by similar to 40%), whereas PDIred diminished (by similar to 60%) superoxide generation. No change occurred after incubation with PDI serine-mutated in all four redox cysteines. Moreover, a mimetic CxxC PDI inhibited superoxide production by similar to 70%. Thus, oxidized PDI supports, whereas reduced PDI down-regulates, intrinsic membrane NADPH oxidase complex activity. In whole neutrophils, immunoprecipitation and colocalization experiments demonstrated PDI association with membrane complex subunits and prominent thiol-mediated interaction with p47(phox) in the cytosol fraction. Upon PMA stimulation, PDI was mobilized from azurophilic granules to cytosol but did not further accumulate in membranes, contrarily to p47(phox). PDI-p47(phox) association in cytosol increased concomitantly to opposite redox switches of both proteins; there was marked reductive shift of cytosol PDI and maintainance of predominantly oxidized PDI in the membrane. Pulldown assays further indicated predominant association between PDIred and p47(phox) in cytosol. Incubation of purified PDI (> 80% reduced) and p47(phox) in vitro promoted their arachidonate-dependent association. Such PDI behavior is consistent with a novel cytosolic regulatory loop for oxidase complex (re) cycling. Altogether, PDI seems to exhibit a supportive effect on NADPH oxidase activity by acting as a redox-dependent enzyme complex organizer. J. Leukoc. Biol. 90: 799-810; 2011.

Digital vasculitis in systemic lupus erythematosus: a minor manifestation of disease activity?

The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity. DV and other clinical manifestations defined according to the SLEDAI were evaluated in 168 consecutive patients with systemic lupus erythematosus (SLE). Two groups were defined according to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time of evaluation. The exclusion criterion was the presence of antiphospholipid syndrome (Sapporo`s criteria). The two groups were comparable with regard to age (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = 0.78). Compared to the DV-group, the DV+ group had a significantly higher frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were similar in both groups ( P = 0.57 and P = 1.00, respectively). The evaluation of each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild disease. The high `weighted` index attributed to this alteration in the SLEDAI score should therefore be revised. Lupus (2009) 18, 990-993.

Absence of galectin-3 does not affect the development of experimental tongue carcinomas in mice

Background: Galectin-3 is a lectin that presents pivotal roles in tumor biology and there are no studies evaluating their expression in dysplasias and carcinomas developed from tongue carcinogenesis models. Aims: To investigate the role of galectin-3 in the development of tongue carcinomas using a mouse model of oral carcinogenesis. Methods: Galectin-3-deficient (gal3(-/-)) and wild-type (gal3(+/+)) mice were challenged with 4-nitroquinoline-1-oxide in drinking water for 16 weeks and killed at different times. Tongues were removed and the number of dysplasias and carcinomas was counted. An immunohistochemical study for galectin-3 was performed only in the tongue from gal3(+/+) mice. Results: In both groups, a reduction of dysplasias and an increase of carcinomas from week 16 to week 32 (p > 0.05) were observed. A predominance of high cytoplasmic and nuclear galectin-3 expression was observed in carcinomas (64.7%) and dysplasias (55.5%), respectively (p > 0.05). The perilesional areas always presented a statistical cytoplasmic and nuclear galectin-3 overexpression. Conclusions: Absence of galectin-3 did not directly affect the process of carcinogenesis and a cytoplasm shift of galectin-3 seems to be associated with development of tongue carcinomas. (C) 2010 Elsevier Inc. All rights reserved.

Phase II Trial of Infusional Fluorouracil, Irinotecan, and Bevacizumab for Metastatic Colorectal Cancer: Efficacy and Circulating Angiogenic Biomarkers Associated With Therapeutic Resistance

Purpose We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)), and leucovorin (400 mg/m(2)) followed by a 46-hour infusion of FU (2,400 mg/m(2)). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001). Conclusion Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.

Renal Cell Carcinoma: T1 and T2 Signal Intensity Characteristics of Papillary and Clear Cell Types Correlated with Pathology

OBJECTIVE. The objective of our study was to describe the T1 and T2 signal intensity characteristics of papillary renal cell carcinoma (RCC) and clear cell RCC with pathologic correlation. MATERIALS AND METHODS. Of 539 RCCs, 49 tumors (21 papillary RCCs and 28 clear cell RCCs) in 45 patients were examined with MRI. Two radiologists retrospectively and independently assessed each tumor`s T1 and T2 signal intensity qualitatively and quantitatively (i.e., the signal intensity [SI] ratio [tumor SI/renal cortex SI]). Of the 49 tumors, 37 (76%) were assessed for pathology features including tumor architecture and the presence of hemosiderin, ferritin, necrosis, and fibrosis. MRI findings and pathology features were correlated. Statistical methods included summary statistics and Wilcoxon`s rank sum test for signal intensity, contingency tables for assessing reader agreement, concordance rate between the two readers with 95% CIs, and Fisher`s exact test for independence, all stratified by RCC type. RESULTS. Papillary RCCs and clear cell RCCs had a similar appearance and signal intensity ratio on T1-weighted images. On T2-weighted images, most papillary RCCs were hypointense (reader 1, 13/21; reader 2, 14/21), with an average mean signal intensity ratio for both readers of 0.67 +/- 0.2, and none was hyperintense, whereas most clear cell RCCs were hyperintense (reader 1, 21/28; reader 2, 17/28), with an average mean signal intensity ratio for both readers of 1.41 +/- 0.4 (p < 0.05). A tumor T2 signal intensity ratio of <= 0.66 had a specificity of 100% and sensitivity of 54% for papillary RCC. Most T2 hypointense tumors exhibited predominant papillary architecture; most T2 hyperintense tumors had a predominant nested architecture (p < 0.05). CONCLUSION. On T2-weighted images, most papillary RCCs are hypointense and clear cell RCCs, hyperintense. The T2 hypointense appearance of papillary RCCs correlated with a predominant papillary architecture at pathology.

Complex distal insertions of the tibialis posterior tendon: detailed anatomic and MR imaging investigation in cadavers

Purpose The purpose of this report was to demonstrate the normal complex insertional anatomy of the tibialis posterior tendon (TPT) in cadavers using magnetic resonance (MR) imaging with anatomic and histologic correlation. Material and methods Ten cadaveric ankles were used according to institutional guidelines. MR T1-weighted spin echo imaging was performed to demonstrate aspects of the complex anatomic distal insertions of the TPT in cadaveric specimens. Findings on MR imaging were correlated with those derived from anatomic and histologic study. Reults Generally, the TPT revealed a low signal in all MR images, except near the level of the medial malleolus, where the TPT suddenly changed direction and ""magic angle"" artifact could be observed. In five out of ten specimens (50%), a type I accessory navicular bone was found in the TPT. In all cases with a type I accessory navicular bone, the TPT had an altered signal in this area. Axial and coronal planes on MR imaging were the best in identifying the distal insertions of the TPT. A normal division of the TPT was observed just proximal to the insertion into the navicular bone in five specimens (100%) occurring at a maximum proximal distance from its attachment to the navicular bone of approximately 1.5 to 2 cm. In the other five specimens, in which a type I accessory navicular bone was present, the TPT directly inserted into the accessory bone and a slip less than 1.5 mm in thickness could be observed attaching to the medial aspect of the navicular bone (100%). Anatomic inspection confirmed the sites of the distal insertions of the components of the TPT. Conclusion MR imaging enabled detailed analysis of the complex distal insertions of the TPT as well as a better understanding of those features of its insertion that can simulate a lesion.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Wilson`s disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

Brain magnetic resonance imaging (MRI) studies on Wilson`s disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.

Exploring the knowledge contained in neuroimages: Statistical discriminant analysis and automatic segmentation of the most significant changes

Objective: The aim of this article is to propose an integrated framework for extracting and describing patterns of disorders from medical images using a combination of linear discriminant analysis and active contour models. Methods: A multivariate statistical methodology was first used to identify the most discriminating hyperplane separating two groups of images (from healthy controls and patients with schizophrenia) contained in the input data. After this, the present work makes explicit the differences found by the multivariate statistical method by subtracting the discriminant models of controls and patients, weighted by the pooled variance between the two groups. A variational level-set technique was used to segment clusters of these differences. We obtain a label of each anatomical change using the Talairach atlas. Results: In this work all the data was analysed simultaneously rather than assuming a priori regions of interest. As a consequence of this, by using active contour models, we were able to obtain regions of interest that were emergent from the data. The results were evaluated using, as gold standard, well-known facts about the neuroanatomical changes related to schizophrenia. Most of the items in the gold standard was covered in our result set. Conclusions: We argue that such investigation provides a suitable framework for characterising the high complexity of magnetic resonance images in schizophrenia as the results obtained indicate a high sensitivity rate with respect to the gold standard. (C) 2010 Elsevier B.V. All rights reserved.

Increased rates of white matter hyperintensities in late-onset bipolar disorder

Objectives: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset 60 years), early-onset BD subjects (EO-BD, illness onset < 60 years), and elderly healthy volunteers. Methods: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. Results: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Conclusions: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these. findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

White-matter hyperintensities in first-episode psychosis

Background White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. Aims To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. Method T-2-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. visual white-matter hyperintensity ratings were used for group and subgroup comparisons. Results There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. Conclusions White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings. Declaration of interest None. Funding detailed in Acknowledgements.

USE OF DISPERSIVE RAMAN SPECTROSCOPY IN THE DETERMINATION OF UNSATURATED FAT IN COMMERCIAL EDIBLE OIL- AND FAT-CONTAINING INDUSTRIALIZED FOODS

The present study aims at the use of Raman spectroscopy in the quantification of unsaturated fats in fat-containing foods, compared to the information available in the Nutritional Table, to obtain a non-destructive optical quantification of unsaturation. Raman spectra of edible oil, margarine, mayonnaise, hydrogenated fat, and butter were obtained with a near-infrared Raman spectrometer (830nm). By analyzing selected bands in the regions of 1750, 1660, 1440, 1300, and 1260cm-1, the amount of total and unsaturated fat of samples of oil, margarine, and mayonnaise were correlated with the information displayed in the Nutritional Table. The amount of unsaturated trans fat in selected samples was correlated to the Raman shift of 1660cm-1. Dispersive Raman spectroscopy was shown to be effective in quantifying the unsaturated fats in oil, margarine, and mayonnaise, and trans fat in hydrogenated oils and butter.

Findings of Pelvic Endometriosis at Transvaginal US, MR Imaging, and Laparoscopy

Endometriosis is a common multifocal gynecologic disease that manifests during the reproductive years, often causing chronic pelvic pain and infertility. It may occur as invasive peritoneal fibrotic nodules and adhesions or as ovarian cysts with hemorrhagic content. Although findings at physical examination may be suggestive, imaging is necessary for definitive diagnosis, patient counseling, and treatment planning. The imaging techniques that are most useful for preoperative disease mapping are transvaginal ultrasonography (US) after bowel preparation, and magnetic resonance (MR) imaging. Initial transvaginal US is a reliable technique for detecting rectosigmoid endometriotic lesions. MR imaging is indicated as a complementary examination in complex cases of endometriosis with extensive adhesions and ureteral involvement. Peritoneal endometriotic implants are typically hypoechoic on transvaginal US images and demonstrate low signal intensity on T2-weighted MR images. Endometriotic implants most commonly are found in retrocervical and rectosigmoid sites, followed by the vagina, bladder, and ureters. Cysts with low-level internal echoes and echogenic peripheral foci at transvaginal US are suggestive of endometriomas. MR imaging has high specificity for identifying endometriomas, which are characterized by high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Correlation of the radiologic imaging features of endometriotic lesions with their laparoscopic appearances may help improve individual proficiency in the radiologic diagnosis of endometriosis. Supplemental material available at http:// radiographics.rsna.org/lookup/suppl/doi: 10.1148/rg.314105193/-/DC1. (C) RSNA, 2011 radiographics.rsna.org