Inflammation and Biochemical Features of Bariatric Candidates: Does Gender Matter?

Background Accumulated fat is an accepted trigger of inflammation and metabolic syndrome but specific biochemical associations in males and females are still debated. In a prospective study, multiple variables were analyzed to search for gender-related correlations. Methods Bariatric candidates (n=94) were consecutively investigated. Age was 34.9 +/- 10.4 years (68.1% females) and body mass index (BMI) was 40.8 +/- 4.6 kg/m(2). Methods included anthropometrics, inflammatory indices (C-reactive protein (CRP), white blood cell count (WBC), ferritin) and general biochemical profile. Results Ferritin, but not CRP or WBC, was substantially more elevated in males. Serum albumin, uric acid, creatinine, and liver enzymes AST and ALT were also higher in men. Even after BMI was adjusted, all differences remained significant, and several, notably ferritin, withstood waist circumference control. Ferritin and CRP correlated with anthropometrics, glucose-related measurements, and liver enzymes, whereas WBC was only associated with triglycerides in females. Conclusions (1) Males displayed more severe inflammation according to ferritin profile, and also more signs of liver derangement; (2) all differences continued after BMI discrepancies were adjusted for, and ferritin was significant also after control of waist girth; (3) in both genders inflammatory markers often correlated with different anthropometrics, liver enzymes, and markers of glucose homeostasis; and (4) inflammatory and biochemical gender-related dissimilarities might have prognostic implications for cardiovascular risk and other comorbidities, and deserve additional studies.

Endoscopic features in a model of multivisceral xenotransplantation

Introduction: Xenotransplantation and multivisceral transplantation are advanced therapeutic methods that still require a scientific basis. There are no experimental models of multivisceral transplantation available, particularly not the monitoring by endoscopy. Here, we describe the endoscopic features in a model of multivisceral xenotransplantation. Methods: The distal esophagus, stomach, intestine, colon, liver, pancreas, and the kidneys with a common vascular pedicle were harvested from rabbits and implanted in swine (group I, n = 9) or in rabbits (group II, n = 4). Endoscopy was performed in the stomach, jejunum, and ascending colon at four consecutive time points (immediate after surgery and 10, 90, and 180 min after reperfusion). Lesions were macroscopically graded as mild, moderate, and severe. Biopsies were taken following sacrifice at 180 min after reperfusion. Results: In group I, the stomach, jejunum, and colon manifested a progression of lesions with predominance of mild lesions after 10 min, mild to moderate lesions after 90 min, and moderate to severe lesions after 180 min. In animals from group II, endoscopy showed normal features at all time points after reperfusion. Histopathologic analysis confirmed the diagnosis of hyperacute rejection in group I. Grafts from group II animals presented normal or mild ischemic/reperfusion injury. Conclusion: All animals subjected to multivisceral xenotransplantation showed a progression of endoscopic lesions with time after transplantation, while animals subjected to allotransplantation showed no aberrations in endoscopy. We conclude that endoscopy is a useful tool in the assessment of hyperacute rejection of a xenograft.

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis

CD40 ligand (CD40-L), a member of the tumor necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. Interactions between CD40-L and CD40 induce B cell immunoglobulin production as well as monocyte activation and dendritic cell differentiation. Since these features characterize rheumatoid arthritis (RA), the expression and function of CD40-L in RA was examined. Freshly isolated RA peripheral blood (PB) and synovial fluid (SF)T cells expressed CD40-L mRNA as well as low level cell surface CD40-L. An additional subset of CD4+ RA SF T cells upregulated cell surface CD40-L expression within 15 min of in vitro activation even in the presence of cycloheximide, but soluble CD40-L was not found in SF. CD40-L expressed by RA T cells was functional, since RA PB and SF T cells but not normal PB T cells stimulated CD40-L-dependent B cell immunoglobulin production and dendritic cell IL-12 expression in the absence of prolonged in vitro T cell activation. In view of the diverse proinflammatory effects of CD40-L, this molecule is likely to play a central role in the perpetuation of rheumatoid synovitis. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.

Mucinous colorectal adenocarcinoma: influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis

Background Mucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed. Materials and Methods Immunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed. Results Of the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression. Conclusions Mucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.

The rms1 mutant of pea has elevated indole-3-acetic acid levels and reduced root-sap zeatin riboside content but increased branching controlled by graft-transmissible signal(s)

Rms1 is one of the series of five ramosus loci in pea (Pisum sativum L.) in which recessive mutant alleles confer increased branching at basal and aerial vegetative nodes. Shoots of the nonallelic rms1 and rms2 mutants are phenotypically similar in most respects. However, we found an up to 40-fold difference in root-sap zeatin riboside ([9R]Z) concentration between rms1 and rms2 plants. Compared with wild-type (WT) plants, the concentration of [9R]Z in rms1 root sap was very low and the concentration in rms2 root sap was slightly elevated. To our knowledge, the rms1 mutant is therefore the second ramosus mutant (rms4 being the first) to be characterized with low root-sap [9R]Z content. Like rms2, the apical bud and upper nodes of rms1 plants contain elevated indole-3-acetic acid levels compared with WT shoots. Therefore, the rms1 mutant demonstrates that high shoot auxin levels and low root-sap cytokinin levels are not necessarily correlated with increased apical dominance in pea. A graft-transmissible basis of action has been demonstrated for both mutants from reciprocal grafts between mutant and WT plants. Branching was also largely inhibited in rms1 shoots when grafted to rms2 rootstocks, but was not inhibited in rms2 shoots grafted to rms1 rootstocks. These grafting results are discussed, along with the conclusion that hormone-like signals other than auxin and cytokinin are also involved.

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat.

Metallic Voice: Physiological and Acoustic Features

The metallic voice is usually confused with ring or nasality by singers and nontrained listeners. who are not used to perceptual vocal analysis. They believe a metallic voice results from a rise in fundamental frequency. A diagnostic error in this aspect may lead to lowering pitch, an incorrect procedure that Could Cause vocal overload and fatigue. The purpose of this article is to Study the quality of metallic voice considering the correlation between information of the physiological and acoustic plans, based on a perceptive consensual assumption. Fiberscopic video pharyngolaryngoscopy was performed on 21 professional singers while speaking vowel [e]-in normal and metallic modes to observe muscular movements and structural changes of the velopharynx, pharynx, and larynx. Vocal samples captured simultaneously to the fiberscopic examination were acoustically analyzed. Frequency and amplitude of the first four formants (F(1), F(2), F(3), and F(4)) were extracted by means of linear predictor coefficients (LPC) Spectrum and were statistically analyzed. Vocal tract adjustments such as velar lowering, pharyngeal wall narrowing, laryngeal rise, aryepiglottic, and lateral laryngeal constrictions were frequently found: there were no significant changes in frequency and amplitude of F(1) in the metallic voiced there were significant increases in amplitudes of F(2), F(3), and F(4) and in frequency for F, metallic Voice perceived as louder was correlated to an increase ill amplitude of F(3) and F(4). Physiological adjustments of velopharynx, pharynx, and larynx are combined in characterizing the metallic voice and can be acoustically related to changes in formant pattern.

Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and continuous immune cell infiltration in the synovium. These changes are linked to inflammatory cytokine release, leading to eventual destruction of cartilage and bone. During the last decade new therapeutic modalities have improved the prognosis, with the introduction of novel biological response modifiers including anti-TNF alpha CTLA4Ig and, more recently, anti-IL6. In the present study we looked at the immunological effects of these three forms of therapy. Serum, obtained from patients with RA was analyzed for TNF alpha, IL6, IL10, IFN gamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid dendritic cells (DC) were enumerated before and after three infusions of the respective biological treatments. After treatment with anti-IL6, we found a significant reduction of IL6 and TNF alpha levels and the percentage of both DC subsets decreased. Although the results did not reach statistical significance for anti-TNF alpha treatment, similar trends were observed. Meanwhile, CTLA4Ig therapy led to the reduction IFN gamma levels only. None of the treatments modified significantly VEGF or IL10 levels. These findings may explain why patients with RA improve more rapidly on IL-6 therapy than with the other two modalities.

Etiological and Clinical Features of Childhood Psychotic Symptoms Results From a Birth Cohort

Context: It has been reported that childhood psychotic symptoms are common in the general population and may signal neurodevelopmental processes that lead to schizophrenia. However, it is not clear whether these symptoms are associated with the same extensive risk factors established for adult schizophrenia. Objective: To examine the construct validity of children`s self-reported psychotic symptoms by testing whether these symptoms share the risk factors and clinical features of adult schizophrenia. Design: Prospective, longitudinal cohort study of a nationally representative birth cohort in Great Britain. Participants: A total of 2232 twelve-year-old children followed up since age 5 years ( retention, 96%). Main Outcome Measure: Children`s self-reported hallucinations and delusions. Results: Children`s psychotic symptoms are familial and heritable and are associated with social risk factors (eg, urbanicity); cognitive impairments at age 5; home-rearing risk factors ( eg, maternal expressed emotion); behavioral, emotional, and educational problems at age 5; and comorbid conditions, including self-harm. Conclusions: The results provide a comprehensive picture of the construct validity of children`s self-reported psychotic symptoms. For researchers, the findings indicate that children who have psychotic symptoms can be recruited for neuroscience research to determine the pathogenesis of schizophrenia. For clinicians, the findings indicate that psychotic symptoms in childhood are often a marker of an impaired developmental process and should be actively assessed.

Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile

Objective: Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree. which included 715 at-risk family members. Design: Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members. Results: Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T,-2.87 +/- 0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients. while marked bone mineral loss in the lumbar spine (T,-1.95 +/- 0.39). with most cancellous bone, and femoral neck (mixed composition: T,-1.48 +/- 0.27) were also present. Conclusions: In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore. we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT.

CD1a and Factor XIIIa Immunohistochemistry in Leprosy: A Possible Role of Dendritic Cells in the Pathogenesis of Mycobacterium leprae Infection

Leprosy is a curable chronic granulomatous infectious disease caused by the bacillus Mycobacterium leprae. This organism has a high affinity for skin and peripheral nerve cells. In the evolution of infections, the immune status of patients determines the disease expression. Dendritic cells are antigen-presenting cells that phagocytose particles and microorganisms. In skin, dendritic cells are represented by epidermal Langerhans cells and dermal dendrocytes, which can be identified by expression of CD1a and factor XIIIa (FXIIIa). In the present study, 29 skin samples from patients with tuberculoid (13 biopsies) and lepromatous (16 biopsies) leprosy were analyzed by immunohistochemistry using antibodies to CD1a and FXIIIa. Quantitative analysis of labeling pattern showed a clear predominance of dendritic cells in tuberculoid leprosy. Difference between the number of positive cells of immunohistochemistry for the CD1a and FXIIIa staining observed in this study indicates a role for dendritic cells in the cutaneous response to leprosy. Dendritic cells may be a determinant of the course and clinical expression of the disease.

Body dysmorphic disorder among dermatologic patients: Prevalence and clinical features

Background: An impairing preoccupation with a nonexistent or slight defect in appearance is the core symptom of body dysmorphic disorder (ODD), a psychiatric condition common in dermatology settings. Objective: We sought to determine the prevalence of ODD in dermatologic patients, comparing general and cosmetic settings, and describing some demographic and clinical characteristics. Methods: In all, 300 patients were consecutively assessed. Screening and diagnoses were performed with validated instruments plus a best estimate diagnosis procedure. The final sample comprised 150 patients in the cosmetic group, 150 patients in the general dermatology group, and 50 control subjects. Standard statistical analyses were performed (chi(2), nonparametric tests, logistic regression). Results: The current prevalence was higher in the cosmetic group (14.0%) compared with general (6.7%) and control (2.0%) groups. No patient had a previous diagnosis. Frequently the reason for seeking dermatologic treatment was not the main ODD preoccupation. Patients with ODD from the cosmetic group were in general unsatisfied with the results of dermatologic treatments. Limitations: Cross-sectional study conducted in a university hospital is a limitation. It is uncertain if the findings can be generalized. Retrospective data regarding previous treatments are not free from bias. Conclusions: BUD is relatively common in a dermatologic setting, especially among patients seeking cosmetic treatments. These patients have some different features compared with general dermatology patients. Dermatologists should be aware of the clinical characteristics of ODD to identify and refer these patients to mental health professionals. (J Am Acad Dermatol 2010;63:235-43.)