Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naive patients

Background: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. Method: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naive OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). Results: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. Conclusions: Building upon preexisting findings, our data with treatment-naive OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions. (C) 2012 Elsevier Ltd. All rights reserved.

Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyositis patients

Objectives To our knowledge, no study assessed simultaneously a variety of organ-specific autoantibodies and the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (ISLE) and juvenile dermatomyositis (JDM). Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. Methods Forty-one JSLE and 41 JDM patients were investigated for autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type I diabetes mellitus (TIDM, autoimmune thyroiditis (AT), autoimmune gastritis and coeliac disease (CD). Patients with positive antibodies were investigated for the respective organ-specific autoimmune diseases. Results Mean age at diagnosis was higher in ISLE compared to JDM patients (10.3 +/- 3.4 vs. 7.3 +/- 3.1 years, p=0.0001). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of TIDM and AT autoantibodies was observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro, anti-Sm, anti-RNP, anti-La and IgG-aCL were observed in JSLE (p<0.05). Organ-specific autoimmune diseases were evidenced only in ISLE patients (24% vs. 0%, p=0.13). Two ISLE patients had TIDM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had CD diagnosis based on iron deficiency anaemia, anti-endomysial antibody, duodenal biopsy compatible to CD and response to a gluten-free diet. Conclusions Organ-specific diseases were observed solely in ISLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up.

Profiling Three-Dimensional Nuclear Telomeric Architecture of Myelodysplastic Syndromes and Acute Myeloid Leukemia Defines Patient Subgroups

Purpose: Myelodysplastic syndromes (MDS) are a group of disorders characterized by cytopenias, with a propensity for evolution into acute myeloid leukemias (AML). This transformation is driven by genomic instability, but mechanisms remain unknown. Telomere dysfunction might generate genomic instability leading to cytopenias and disease progression. Experimental Design: We undertook a pilot study of 94 patients with MDS (56 patients) and AML (38 patients). The MDS cohort consisted of refractory cytopenia with multilineage dysplasia (32 cases), refractory anemia (12 cases), refractory anemia with excess of blasts (RAEB) 1 (8 cases), RAEB2 (1 case), refractory anemia with ring sideroblasts (2 cases), and MDS with isolated del(5q) (1 case). The AML cohort was composed of AML-M4 (12 cases), AML-M2 (10 cases), AML-M5 (5 cases), AML-M0 (5 cases), AML-M1 (2 cases), AML-M4eo (1 case), and AML with multidysplasia-related changes (1 case). Three-dimensional quantitative FISH of telomeres was carried out on nuclei from bone marrow samples and analyzed using TeloView. Results: We defined three-dimensional nuclear telomeric profiles on the basis of telomere numbers, telomeric aggregates, telomere signal intensities, nuclear volumes, and nuclear telomere distribution. Using these parameters, we blindly subdivided the MDS patients into nine subgroups and the AML patients into six subgroups. Each of the parameters showed significant differences between MDS and AML. Combining all parameters revealed significant differences between all subgroups. Three-dimensional telomeric profiles are linked to the evolution of telomere dysfunction, defining a model of progression from MDS to AML. Conclusions: Our results show distinct three-dimensional telomeric profiles specific to patients with MDS and AML that help subgroup patients based on the severity of telomere dysfunction highlighted in the profiles. Clin Cancer Res; 18(12); 3293-304. (C) 2012 AACR.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

A novel specific genetic translocation in epithelioid hemangioendotelioma, showing a fusion of the WWTR1 and CAMTA1 genes, supports the monoclonality of multifocal epithelioid hemangioendotelioma.

Like other vascular tumors, epithelioid hemangioendothelioma (EHE) is multifocal in approximately 50% of cases, and it is unclear whether the separate lesions represent multifocal disease or metastases. We hypothesized that the identification of an identical WWTR1-CAMTA1 rearrangement in different EHEs from the same patient supports the monoclonal origin of EHE. To test our hypothesis, we undertook a molecular analysis of two multicentric EHEs of the liver, including separate tumor samples from each patient. Matherial and Methods: We retrieved two cases of EHE with available tissue for molecular analysis. In both cases, fluorescence in situ hybridization (FISH) was performed to identify the presence of the WWTR1-CAMTA1 rearrangement to confirm the histologic diagnosis of EHE, as previously described. The reverse transcription-polymerase chain reaction (RT-PCR) products were analyzed by electrophoresis and the RT-PCR–amplified products were sequenced using the Sanger method. Results: FISH analysis revealed signal abnormalities in both WWTR1 and CAMTA1. Combined results confirmed the presence of the t(1;3)(1p36.23;3q25.1) translocation in both cases of EHE. Using RT-PCR analysis, we found that the size of the rearranged bands was identical in the different tumors from each patient. The sequence of the fusion gene confirmed a different WWTR1-CAMTA1 rearrangement in each patient, but an identical WWTR1-CAMTA1 rearrangement in the different lesions from each patient. Discussion: Because of its generally indolent clinical course, EHE is commonly classified as a multifocal, rather than metastatic, disease. In this study, we examined two cases of multifocal liver EHE and found an identical WWTR1-CAMTA1 rearrangement in each lesion from the same patient, but not between the two patients. These findings suggest that multifocal EHE arises from metastasis of the same neoplastic clone rather than from the simultaneous formation of multiple neoplastic clones, which supports the monoclonal origin of multifocal EHE.

Mandibular implant overdentures followed for over 10 years: patient compliance and prosthetic maintenance

PURPOSE: The mandibular implant overdenture is a popular treatment modality and is well documented in the literature. Follow-up studies with a long observation period are difficult to perform due to the increasing age of patients. The present data summarize a long-term clinical observation of patients with implant overdentures. MATERIALS AND METHODS: Between 1984 and 1997, edentulous patients were consecutively admitted for treatment with an implant overdenture. The dentures were connected to the implants by means of bars or ball anchors. Regular maintenance was provided with at least one or two scheduled visits per year. Recall attendance and reasons for dropout were analyzed based on the specific history of the patient. Denture maintenance service, relining, repair, and fabrication of new dentures were identified, and complications with the retention devices specified separately. RESULTS: In the time period from 1984 to 2008, 147 patients with a total of 314 implants had completed a follow-up period of >10 years. One hundred one patients were still available in 2008, while 46 patients were not reexamined for various reasons. Compliance was high, with a regular recall attendance of >90%. More than 80% of dentures remained in continuous service. Although major prosthetic maintenance was rather low in relation to the long observation period, visits to a dental hygienist and dentist resulted in an annual visit rate of 1.5 and 2.4, respectively. If new dentures became necessary, these were made in student courses, which increased the treatment time and number of appointments needed. Complications with the retention devices consisted mostly of the mounting of new female retainers, the repair of bars, and the changing of ball anchors. The average number of events and the rate of prosthetic service with ball anchors were significantly higher than those with bars. Twenty-two patients changed from ball anchors to bars; 9 patients switched from a clip bar to a rigid U-shaped bar. CONCLUSIONS: This long-term follow-up study demonstrates that implant overdentures are a favorable solution for edentulous patients with regular maintenance. In spite of specific circumstances in an aging population, it is possible to provide long-term care, resulting in a good prognosis and low risk for this treatment modality. For various reasons the dropout rate can be considerable in elderly patients and prosthetic service must be provided regularly.

Effectiveness of protective patient equipment for CT: an anthropomorphic phantom study

Protective patient equipment for CT examinations is not routinely provided. The aim of this study was to determine whether, and if so what, specific protective equipment is beneficial during CT scans. The absorbed organ doses and the effective doses for thorax, abdomen/pelvis and brain CT investigation with and without the use of protective patient equipment have been determined and compared. All measurements were carried out on modern multislice CT scanner using an anthropomorphic phantom and thermoluminescence dosemeters. The measurements show that protective equipment reduces the dose within the scattered beam area. The highest organ dose reduction was found in organs that protrude from the trunk like the testes or the female breasts that can largely be covered by the protective equipment. The most reduction of the effective dose was found in the male abdomen/pelvis examination (0.32 mSv), followed by the brain (0.11 mSv) and the thorax (0.06 mSv). It is concluded that the use of protective equipment can reduce the applied dose to the patient.

Adopting a family approach to theory and practice: measuring distress in cancer patient-partner dyads with the distress thermometer

Objective: Significant others are central to patients' experience and management of their cancer illness. Building on our validation of the Distress Thermometer (DT) for family members, this investigation examines individual and collective distress in a sample of cancer patients and their matched partners, accounting for the aspects of gender and role. Method: Questionnaires including the DT were completed by a heterogeneous sample of 224 couples taking part in a multisite study. Results: Our investigation showed that male patients (34.2%), female patients (31.9%), and male partners (29.1%) exhibited very similar levels of distress, while female partners (50.5%) exhibited much higher levels of distress according to the DT. At the dyad level just over half the total sample contained at least one individual reporting significant levels of distress. Among dyads with at least one distressed person, the proportion of dyads where both individuals reported distress was greatest (23.6%). Gender and role analyses revealed that males and females were not equally distributed among the four categories of dyads (i.e. dyads with no distress; dyads where solely the patient or dyads where solely the partner is distressed; dyads where both are distressed). Conclusion: A remarkable number of dyads reported distress in one or both partners. Diverse patterns of distress within dyads suggest varying risks of psychosocial strain. Screening patients' partners in addition to patients themselves may enable earlier identification of risk settings. The support offered to either member of such dyads should account for their role- and gender-specific needs. Copyright © 2010 John Wiley ; Sons, Ltd.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

The Bern psychopathology scale for the assessment of system-specific psychotic symptoms

The translation from psychiatric core symptoms to brain functions and vice versa is a largely unresolved issue. In particular, the search for disorders of single brain regions explaining classical symptoms has not yielded the expected results. Based on the assumption that the psychopathology of psychosis is related to a functional imbalance of higher-order brain systems, the authors focused on three specific candidate brain circuitries, namely the language, and limbic and motor systems. These domains are of particular interest for understanding the disastrous communication breakdown during psychotic disorders. Core symptoms of psychosis were mapped on these domains by shaping their definitions in order to match the related brain functions. The resulting psychopathological assessment scale was tested for interrater reliability and internal consistency in a group of 168 psychotic patients. The items of the scale were reliable and a principal component analysis (PCA) was best explained by a solution resembling the three candidate systems. Based on the results, the scale was optimized as an instrument to identify patient subgroups characterized by a prevailing dysfunction of one or more of these systems. In conclusion, the scale is apt to distinguish symptom domains related to the activity of defined brain systems. PCA showed a certain degree of independence of the system-specific symptom clusters within the patient group, indicating relative subgroups of psychosis. The scale is understood as a research instrument to investigate psychoses based on a system-oriented approach. Possible immediate advantages in the clinical application of the understanding of psychoses related to system-specific symptom domains are also discussed.

Femur Specific Polyaffine Model to Regularize the Log-Domain Demons Registration

Osteoarticular allograft transplantation is a popular treatment method in wide surgical resections with large defects. For this reason hospitals are building bone data banks. Performing the optimal allograft selection on bone banks is crucial to the surgical outcome and patient recovery. However, current approaches are very time consuming hindering an efficient selection. We present an automatic method based on registration of femur bones to overcome this limitation. We introduce a new regularization term for the log-domain demons algorithm. This term replaces the standard Gaussian smoothing with a femur specific polyaffine model. The polyaffine femur model is constructed with two affine (femoral head and condyles) and one rigid (shaft) transformation. Our main contribution in this paper is to show that the demons algorithm can be improved in specific cases with an appropriate model. We are not trying to find the most optimal polyaffine model of the femur, but the simplest model with a minimal number of parameters. There is no need to optimize for different number of regions, boundaries and choice of weights, since this fine tuning will be done automatically by a final demons relaxation step with Gaussian smoothing. The newly developed synthesis approach provides a clear anatomically motivated modeling contribution through the specific three component transformation model, and clearly shows a performance improvement (in terms of anatomical meaningful correspondences) on 146 CT images of femurs compared to a standard multiresolution demons. In addition, this simple model improves the robustness of the demons while preserving its accuracy. The ground truth are manual measurements performed by medical experts.

Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells

T-cells specific for foreign (e.g., viral) antigens can give rise to strong protective immune responses, whereas self/tumor antigen-specific T-cells are thought to be less powerful. However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients. Here we analyzed the functionality of these T-cells directly ex vivo, by multiparameter flow cytometry. The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways. Interestingly, high frequencies of functionally competent T-cells were induced irrespective of patient's age or gender. Finally, CD8 T-cell function correlated with disease-free survival. However, this result is preliminary since the study was a Phase I clinical trial. We conclude that human tumor-specific CD8 T-cells can reach functional competence in vivo, encouraging further development and Phase III trials assessing the clinical efficacy of robust vaccination strategies.

Patient with syncope and LQTS carrying a mutation in the PAS domain of the hERG1 channel

We report the case of a woman with syncope and persistently prolonged QTc interval. Screening of congenital long QT syndrome (LQTS) genes revealed that she was a heterozygous carrier of a novel KCNH2 mutation, c.G238C. Electrophysiological and biochemical characterizations unveiled the pathogenicity of this new mutation, displaying a 2-fold reduction in protein expression and current density due to a maturation/trafficking-deficient mechanism. The patient's phenotype can be fully explained by this observation. This study illustrates the importance of performing genetic analyses and mutation characterization when there is a suspicion of congenital LQTS. Identifying mutations in the PAS domain or other domains of the hERG1 channel and understanding their effect may provide more focused and mutation-specific risk assessment in this population.

Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma

BACKGROUND: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC). METHODS: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival. RESULTS: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220). CONCLUSIONS: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Cancer 2011;. © 2011 American Cancer Society.

Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: results from a prospective population pharmacokinetic study

This study was initiated to assess the quantitative impact of patient anthropometrics and dihydropyrimidine dehydrogenase (DPYD) mutations on the pharmacokinetics (PK) of 5-fluorouracil (5FU) and to explore limited sampling strategies of 5FU.