Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas

Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally aggressive tumor characterized by irregular vessels embedded. in a fibrous stroma. Excessive vascularity results in bleeding complications, and the inhibition of angiogenesis is a promising strategy for managing extensive JNA tumors. To better characterize the endothelial components of JNA, we aimed to evaluate markers of vascular differentiation and proliferation, such as friend leukemia integration-1 (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT-1, a diagnostic marker that discriminates between hemangiomas and vascular malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and secreted acid protein rich in cysteine (SPARC). Antigens were assessed immunohistochemically in vessels and stromal cells of JNA archival cases (n=22). JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls. JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed positive staining. The presence of markers of endothelial differentiation and proliferation highlighted the hyper-proliferative state of JNA vessels. The absence of podoplanin and VEGFR3 underscores their blood endothelial cell characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3 and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a compensatory signaling for controlling angiogenesis. Some of these markers may eventually serve as therapeutic targets. Our results may aid in the understanding of JNA pathophysiology.

PREDICTIVE FACTORS OF GAIT IN NEUROPATHIC AND NON-NEUROPHATIC DIABETIC PATIENTS

Objective: The purpose of this study was to analyze the range of movement of the ankle and the vertical ground reaction force involved in gait among diabetic patients with and without peripheral neuropathy. Sample and Method: 36 individuals were divided into three groups: Control group - CG: 10 individuals without diabetes, Diabetic group - DG: 10 individuals with diabetes without peripheral neuropathy and Neuropathy, and Diabetic neuropathic group - DNG: 16 individuals with diabetes and peripheral diabetic neuropathy. Gait - AMTI (R) OR6/6m and range of tibiotarsal joint movement - System Vicom 640 (R) was carried out in all the participants. Results: The first and second vertical ground reaction force peaks were statistically higher in the neuropathy group, and the range of ankle motion was lower in the Diabetes and Neuropathy groups. Conclusion: The range of movement of the tibiotarsal joint is lower in diabetics, regardless of the presence or absence of peripheral neuropathy, and diabetics with peripheral neuropathy show an increase in the first and second vertical ground reaction force peaks during walking.

Obsessive-compulsive symptoms and disorder in patients with schizophrenia treated with clozapine or haloperidol

We conducted a cross-sectional study to compare the prevalence and severity of obsessive-compulsive symptoms (OCSs) and obsessive-compulsive disorder (OCD) in patients with schizophrenia treated with clozapine or haloperidol. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorders-patient edition was used to diagnose schizophrenia and OCD. Sixty subjects, 40 of them using clozapine and 20 using haloperidol, completed the Yale-Brown Obsessive-Compulsive Scale, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression. The prevalence of OCD in patients taking clozapine was 20%, whereas the prevalence of patients taking haloperidol was 10%, although this difference was not statistically significant (P = .540). However, patients using clozapine showed higher severity of OCSs than patients using haloperidol (P = .027) did. When schizophrenia patients were divided according to the presence or absence of OCD or OCSs, patients with schizophrenia and OCD or OCSs showed higher severity of schizophrenia symptoms when compared to those with schizophrenia without OCD and OCSs (P = .002). A PANSS total score higher than 70 and the use of antidepressants were predictors of the presence of OCSs or OCD. Schizophrenia patients taking clozapine had higher severity scores both in obsessive-compulsive and schizophrenia rating scales. These results may support an association between the exacerbation of obsessive-compulsive phenomena and the use of clozapine. (C) 2009 Elsevier Inc. All rights reserved.

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients

Human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and -2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co-infected subjects may be at increased risk for tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)-like. To study the prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) among coinfected HIV-1/HTLV-1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV-1-infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases ""Emilio Ribas,"" in Sao Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. Results: A total of 38 HIV-1/HTLV-1 co-infected subjects were identified in this cohort: Twenty-six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co-infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow-up. No modifications on HIV-1 viral load was seen. In contrast, the co-infected with TSP/HAM-like group showed higher HTLV-1 proviral load (505 +/- 380 vs. 97 +/- 149 copies/10(4) PBMC, P= 0.012) than asymptomatic co-infected subjects, respectively. The incidence of myelopathy among HIV-1/HTLV-1 co-infected subjects is probably higher than among patients infected only with HTLV-1, and related to a higher HTLV-1 proviral load. Thus, HTLV-1/2 screening should be done for all HIV-1-infected patients in areas where HTLV-1 infection is endemic.

The presence of a vocal ligament in fetuses: a histochemical and ultrastructural study

Although it is currently believed that the vocal ligament of humans undergoes considerable development postnatally, there is no consensus as to the age at which it first emerges. In the newborn infant, the lamina propria has been described as containing a sparse collection of relatively unorganized fibres. In this study we obtained larynges from autopsy of human fetuses aged 7-9 months and used light and electron microscopy to study the collagenous and elastic system fibres in the lamina propria of the vocal fold. Collagen fibres were viewed using the Picrosirius polarization method and elastic system fibres were stained using Weigert`s resorcin-fuchsin after oxidation with oxone. The histochemical and electron microscopic observations were consistent, showing collagen populations with an asymmetric distribution across different compartments of the lamina propria. In the central region, the collagen appeared as thin, weakly birefringent, greenish fibres when viewed using the Picrosirius polarization method, whereas the superficial and deep regions contained thick collagen fibres that displayed a strong red or yellow birefringence. These findings suggest that the thin fibres in the central region consist mainly of type III collagen, whereas type I collagen predominates in the superficial and deep regions, as has been reported in studies of adult vocal folds. Similarly, elastic system fibres showed a differential distribution throughout the lamina propria. Their distribution pattern was complementary to that of collagen fibres, with a much greater density of elastic fibres apparent in the central region than in the superficial and deep regions. This distribution of collagen and elastic fibres in the fetal vocal fold mirrors that classically described for the adult vocal ligament, suggesting that a vocal ligament has already begun to develop by the time of birth. The apparently high level of organization of connective tissue components in the newborn is in contrast to current hypotheses that argue that the mechanical stimuli of phonation are essential to the determination of the layered structure of the lamina propria and suggests that genetic factors may play a more significant role in the development of the vocal ligament than previously believed.

Anaplastic Thyroid Carcinoma Morphologic Findings and PAX-8 Expression in Cytology Specimens

Objective To evaluate the morphologic findings most encountered in anaplastic thyroid carcinomas (ATCs) and evaluate for the expression of PAX-8. Study Design The cytology specimens from 21 cases of ATC were evaluated for the following several cytologic criteria, cell morphology, pleomorphism, presence or absence of multinucleated cells, neutrophilic infiltrate and well-differentiated component. Immunohistochemical studies for PAX-8 were performed on cell blocks in selected cases. Results The most common morphology present was epithelioid, followed by spindle, multinucleated giant cell and rhabdoid, with 75% demonstrating more than 1 cell morphology. Marked pleomorphism (81%), neutrophilic infiltrate (90%) and necrosis (63%) were frequent. No nuclear grooves, colloid or well-differentiated component was idenrifled in any case. Immunocytochemical stains for PAX-8 were negative in 5 cases in which a cell block was available. Conclusion ATC is a tumor with diverse morphologic characteristics, and more than 1 cell morphology is usually present A neutrophilic infiltrate is a common finding and represents a clue to the correct diagnosis. (Acta Cytol 2010;54:668-672)

Dental Evaluation of Kabuki Syndrome Patients

Kabuki syndrome is a genetic disorder of unknown etiology characterized by mental retardation, growth deficiency, and peculiar face (i.e., long palpebral fissures, eversion of the lateral third of the lower eyelids, prominent ears, and broad and depressed nasal tip). Oral manifestations commonly observed in Kabuki syndrome may comprise cleft lip/palate, bifid tongue and uvula, malocclusion, and dental abnormalities. We evaluated the dental findings of eight patients with Kabuki syndrome. One presented cleft palate; three presented caries; and seven had missing teeth, with the upper lateral incisors and inferior central incisors being the most commonly absent. All missing teeth were permanent, and there was no alteration of dental chronology or morphology. Because most patients had mixed dentition, the presence or absence of primary teeth was assessed through the parents` reports. One patient presented an absent upper canine, which had not been reported previously in the literature. Dental findings may be helpful for clinical diagnosis, or they may be an additional finding to substantiate the diagnosis of Kabuki syndrome in children with mild phenotype.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer.

The Elevated Interferon Gamma Production is an Important Immunological Marker in HAM/TSP Pathogenesis

Human T-lymphotropic virus type 1 (HTLV-1) is the agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may Occur in > 5% of patients during their lifetime. HTLV-1-infection causes disturbances in the immune system, and the viral load may also play an important role in the pathogenesis of HAM/TSP. Some cytokines are involved in the pathogenesis of this disorder. We have determined IL-2, IL-4, IL-10, IL-12 p70, IFN-gamma and TNF-alpha production among HTLV-1-infected subjects from our HTLV-out Clinic in Institute of Infectious `Emilio Ribas` in Sao Paulo city, Brazil. PBMC obtained from healthy controls (n = 32), asymptomatic HTLV-1 carriers (n = 68) and HAM/TSP patients (n = 44) were grown in the absence and in the presence of phytohaemagglutinin (PHA), and the supernatants` fluids were measured for cytokines production. IL-2 levels were increased in the a-symptomatic HTLV-1 carriers, and IFN-gamma was increased in both groups of patients (asymptomatic HTLV-1 carriers and more significantly among HAM/TSP patients). IL-4, IL-10, TNF-alpha and IL-12 p70 levels were not significantly increased on both groups of patients, as compared with controls. The major finding Of this Study is that IFN-gamma was an important cytokine for the HAM/TSP pathogenesis. Therefore, immune modulation of IFN-gamma may be critical to treat of HAM/TSP patients.

Absence of bifurcation of the portal vein

Absence of the horizontal segment of the left portal vein (PV) or absence of bifurcation of the portal vein (ABPV) is extremely rare anomaly. The aim of this study was to study the extra-hepatic PV demonstrating the importance of its careful assessment for the purpose of split-liver transplantation. Human cadaver livers (n = 60) were obtained from routine autopsies. The cutting plane of the liver consisted of a longitudinal section made immediately on the left of the supra-hepatic inferior vena cava through the gallbladder bed preserving the arterial, portal and biliary branches in order to obtain two viable grafts (right lobe-segments V, VI, VII, and VIII and left lobe-segments II, III, and IV) as defined by the main portal scissure. The PV was dissected out and recorded for application of the liver splitting. The PV trunk has been divided into right and left branch in 50 (83.3%) cases. A trifurcation of the PV was found in 9 (15.2%) cases, 3 (5%) was a right anterior segmental PV arising from the left PV and 6 (10%) a right posterior segmental PV arising from the main PV. ABPV occurred in 1 (1.6%) case. Absence of bifurcation of the portal vein is a rare anatomic variation, the surgeon must be cautious and aware of the existence of this exceptional PV anomaly either pre or intra-operatively for the purpose of hepatectomies or even split-liver transplantation.

Pulmonary involvement in pleural tuberculosis: How often does it mean disease activity?

Objective: To evaluate in chest X-rays and high-resolution computed tomographies of patients with pleural tuberculosis, the incidence of parenchymal and mediastinal lung lesions suggestive of active disease. Methods: Prospective study (2008-2009) evaluating the radiographic and tomographic abnormalities of 88 HIV-negative patients with pleural tuberculosis (unilateral effusion). The images were reviewed by 3 independent specialists, and the observed changes were classified according to previously established criteria: presence or absence of signs suggestive of disease activity, and nonspecific findings. Results: Abnormal changes were observed in chest X-rays of 22 (25%) patients and in the computed tomography of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by radiography in 9 (10%) patients and by tomography in 38 (43%). Only 4 (4.5%) patients had tomography images suggestive of residual disease. Conclusion: The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis. This finding is mainly observed in high-resolution computed tomography and has important epidemiological implications, since patients with pleural tuberculosis are significant sources of infection and disease dissemination. (C) 2011 Elsevier Ltd. All rights reserved.

Epstein-Barr virus detection in invasive and pre-invasive lesions of the uterine cervix

In the present study, our aim was to investigate whether EBV DNA could be found in association with invasive and pre-invasive cervical cancer lesions. We hypothesize that EBV is not merely a commensal agent when present in malignant cervical lesions. DNA was extracted from cervical scrapings followed by nested PCR-based amplification. The patients were 66 women with high grade cervical intraepithelial neoplasia and 14 women with invasive cervical cancer. The control group consisted of 89 women with a normal Pap smear and colposcopy as well as a negative HPV DNA test. Analysis of our results, in conjunction with the work of other authors, leads us to propose that EBV is not merely a commensal agent when present in malignant cervical lesions. The presence of DNA from EBV is significantly associated with cervical cancer.

Presence of residual basal cell carcinoma in re-excised specimens is more probable when deep and lateral margins were positive

In order to quantify presence of residual BCC in patients with histologic positive margins after the first excison and to correlate the presence of residual tumor in re-excised lesions with the location of the positive margin on the first excision, a retrospective evaluation of 2053 surgically treated BCC was performed. Only 38.3% of the re-excised lesions showed residual tumor. In the group of re-excised lesions where residual BCC was found, 13% had lateral positive margin in the first excision, 39% had deep positive margin and 48% had both lateral and deep positive margins. In the group of re-excised lesions where no residual BCC was found, 49% of the primary excised lesions had lateral positive margin, 32% had deep positive margin and 19% had both deep and lateral positive margins. The association between residual tumor and positive margins was statistically significant (p = 0.01). Our findings confirm that presence of residual tumour is more likely when both lateral and deep margins are compromised.

Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0-5 years in Brazil

Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected. (C) 2010 Elsevier B.V. All rights reserved.

Immunolocalization and pathological alterations following Strongyloides venezuelensis infection in the lungs and the intestine of MHC class I or II deficient mice

The present study, investigated the mechanisms involved in the immune responses of Major Histocompatibility Complex class I or class II knockout mice, following Strongyloides venezuelensis infection. Wild-type C57BL/6 (WT), MHC II(-/-) and MHC I(-/-) mice were individually inoculated with 3000 larvae (U) of S. venezuelensis and sacrificed on days 1, 3, 5, 8, 13 and 21 post-infection (p.i.). Samples of blood, lungs and small intestines were collected. The tissue samples were stained with hematoxylineosin for the pathological analysis. The presence of the parasite was demonstrated by immunoperoxidase analysis. MHC II(-/-) mice presented a significantly higher number of adult worms recovered from the small intestine on day 5 p.i. and presented elevated numbers of eggs in the feces. The infection by S. venezuelensis was completely eliminated 13 days after infection in WT as well as in MHC I(-/-) mice. In MHC II(-/-) mice, eggs and adult worms were still found on day 21 p.i., however, there was a significant reduction in their numbers. In the lung, the parasite was observed in MHC I(-/-) on day 1 p.i. and in MHC II(-/-) mice on days 1 and 5 p.i. In the small intestine of WT mice, a larger number of parasites were observed on day 8 p.i. and their absence was observed after day 13 p.i. Through immunohistochemistry analysis, the parasite was detected in the duodenum of WT on days 5 and 8 p.i., and in knockout mice on days 5, 8 and 13 p.i.; as well as in posterior portions of the small intestine in MHC I(-/-) and MHC II(-/-) on day 13 p.i., a finding which was not observed in WT mice. We concluded that immunohistochemistry analysis contributed to a more adequate understanding of the parasite localization in immunodeficient hosts and that the findings aid in the interpretation of immunopathogenesis in Strongyloides infection. (C) 2008 Elsevier B.V. All rights reserved.