HFE gene mutations in patients with primary iron overload: Is there a significant improvement in molecular diagnosis yield with HFE sequencing?

Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation >50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n = 11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and beta 2-microglobulin ((beta 2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. (C) 2010 Elsevier Inc. All rights reserved.

Prerequisite Programs at Schools: Diagnosis and Economic Evaluation

In this study, 20 Brazilian public schools have been assessed regarding good manufacturing practices and standard sanitation operating procedures implementation. We used a checklist comprised of 10 parts ( facilities and installations, water supply, equipments and tools, pest control, waste management, personal hygiene, sanitation, storage, documentation, and training), making a total of 69 questions. The implementing modification cost to the found nonconformities was also determined so that it could work with technical data as a based decision-making prioritization. The average nonconformity percentage at schools concerning to prerequisite program was 36%, from which 66% of them own inadequate installations, 65% waste management, 44% regarding documentation, and 35% water supply and sanitation. The initial estimated cost for changing has been U.S.$24,438 and monthly investments of 1.55% on the currently needed invested values. This would result in U.S.$0.015 increase on each served meal cost over the investment replacement within a year. Thus, we have concluded that such modifications are economically feasible and will be considered on technical requirements when prerequisite program implementation priorities are established.

Lead in saliva from lead-exposed and unexposed children

Introduction: Whole blood is used for diagnosis of lead exposure. A non-invasive method to obtain samples for the biomonitoring of lead contamination has become a necessity. This study 1) compares the lead content in whole saliva samples (Pb-saliva) of children from a city with no reported lead contamination (Ribeirao Preto, Sao Paulo State, Brazil) and children of a region notoriously contaminated with lead (Bauru, Sao Paulo State, Brazil), and 2) correlates Pb-saliva with the lead content in the enamel microbiopsy samples (Pb-enamel) in the case of these two populations. Methods: From a population of our previous study that had included 247 children (4- to 6-year-old) from Ribeirao Preto, and 26 children from Bauru, Pb-saliva was analyzed in 125 children from Ribeirdo Preto and 19 children from Bauru by inductively coupled plasma mass spectrometry (ICPMS). To correlate Pb-saliva with Pb-enamel, we used Pb-enamel data obtained in our previous study. The Mann-Whitney test was employed to compare the Pb-saliva data of the two cities. Pb-saliva and Pb-enamel values were then Log(10) transformed to normalize data, and Pb-saliva and Pb-enamel were correlated using Pearson`s correlation coefficient. Results: Median Pb-saliva from the Ribeirao Preto population (1.64 mu g/L) and the Bauru population (5.85 mu g/L) were statistically different (p<0.0001). Pearson`s correlation coefficient for Log(10) Pb-saliva versus Log(10) Pb-enamel was 0.15 (p=0.08) for Ribeirao Preto and 0.38 (p=0.11) for Bauru. Conclusions: A clear relationship between Pb-saliva and environmental contamination by lead is shown. Further studies on Pb-saliva should be undertaken to elucidate the usefulness of saliva as a biomarker of lead exposure, particularly in children. (C) 2008 Elsevier B.V. All rights reserved.

Diagnosis of Organizational Soft Problems in a Peruvian Financial Institution by Systemic Thinking

Managing financial institutions in an underdeveloped economic context has become a real challenge nowadays. In order to reach the organization`s planned goals, they have to deal with structural, behavioral and informational problems. From the systemic point of view, this situation gets even worse when the company does not present organizational boundaries and a cohesive identification for their stakeholders. Thus, European countries have some special financial lines in order to help the development of micro credit in Latin communities in an attempt to help the local economy. However, institutions like Caixa dos Andes in Peru present management problems when dealing with this complexity. Based on this, how can the systemic eye help in the diagnosis of soft problems of a Peruvian financial company? This study aims to diagnose soft problems of a Peruvian financial company based on soft variables like identity, communication and autonomy and also intends to identify possible ways to redesign its basic framework. The (VSM--Viable System Model) method from Beer (1967), applied in this diagnostic study, was used in a practical way as a management tool for organizations` analysis and planning. By describing the VSM`s five systems, the creation of a systemic vision or a total vision is possible, showing the organization`s complexity from the inside. Some company`s soft problems like double control, inefficient use of physical and human resources, low information flows, slowness, etc. The VSM presented an organizational diagnosis indicating effective solutions that do integrate its five systems.

Systemic Model for Diagnosis of the Micro, Small and Medium Enterprises from Two Cities from the Countryside of the State of So Paulo in Brazil

This article presents a proposal of a systemic model composed for the micro and small companies (MSE) of the region of Ribeiro Preto and the agents which influenced their environment. The proposed model was based on Stafford Beer`s (Diagnosing the system for organizations. Chichester, Wiley, 1985) systemic methodologies VSM (Viable System Model) and on Werner Ulrich`s (1983) CSH (Critical Systems Heuristics). The VSM is a model for the diagnosis of the structure of an organization and of its flows of information through the application of the cybernetics concepts (Narvarte, In El Modelo del Sistema Viable-MSV: experiencias de su aplicacin en Chile. Proyecto Cerebro Colectivo del IAS, Santiago, 2001). On the other hand, CSH focus on the context of the social group applied to the systemic vision as a counterpoint to the organizational management view considered by the VSM. MSE of Ribeiro Preto and Sertozinho had been analyzed as organizations inserted in systems that relate and integrate with other systems concerning the public administration, entities of representation and promotion agencies. The research questions: which are the bonds of interaction among the subsystems in this process and who are the agents involved? The systemic approach not only diagnosed a social group, formed by MSE of Ribeiro Preto and Sertozinho, public authorities and support entities, but could also delineate answers that aimed the clarification of obscure questions generating financial assistance to the formularization of efficient actions for the development of this system.

Redescription of Riethia truncatocaudata (Edwards, 1931) (Diptera: Chironomidae), with description of female, pupa and larva and generic diagnosis for Riethia

The discovery of the immature life history stages of Riethia truncatocaudata (Edwards, 1931) from South America allows diagnosis of Riethia Kieffer, 1917 in all stages, incorporating reared species from the complete austral range. Pseudochironomus truncatocaudata Edwards, 1931 is a senior synonym (syn. n.) of Pseudochironomus melanoides Edwards, 1931. We redescribe the male to complement the short original descriptions of R. truncatocaudata and R. melanoides. The species is congeneric with Australian Riethia stictoptera Kieffer, the type species of the genus Riethia. Extensive material available from the western Pacific (Australia, New Zealand and New Caledonia) confirms that the diagnosis extends to a gondwanan clade, likely sister group to the largely northern genus Pseudochironomus Kieffer.

Study of acetylcholinesterase activity in rectal suction biopsy for diagnosis of intestinal dysganglionoses: 17-year experience of a single center

Although the utility of the acetylcholinesterase (AChE) histochemistry on rectal suction biopsy in diagnosing Hirschsprung`s disease (HD) has been documented, few reports address a great number of biopsies and patients. Our aim is to present a 17-year experience on the method of rectal suction biopsy and AChE histochemical staining for diagnosis of intestinal dysganglionoses. Between August 1989 and July 2006, 297 children suspected of having HD were submitted to rectal suction biopsies that were evaluated by the same two surgeons. There were 18 complications (6.0%), namely one self-limited rectal bleeding and 17 (5.7%) inadequate procedures that were repeated. A total of 157 patients (52.8%) showed no increased AChE activity and the remaining patients (140-47.2.0%) presented patterns of increased AChE activity confirming the diagnosis of HD or neuronal intestinal dysplasia. Among the 140 cases suspected as having HD, in 131 children the diagnosis of HD was confirmed and they were operated on. The histological studies showed that 111 children presented the classic form of HD or a long spastic segment. Sixteen children presented total colonic aganglionosis and four children proved to have intestinal neuronal dysplasia, according to histological and radiological criteria. Nine (6.6%) newborns were identified as false-positives and no false-negative results were verified. The rectal suction biopsy combined with AChE staining is advantageous for the differentiation between normal bowel and intestinal dysganglionoses. The rectal suction method is simple and can easily be performed by experienced surgeons. The histological evaluation is very objective and can be performed by a non-pathologist.

Improving Alzheimer`s Disease Diagnosis with Machine Learning Techniques

There is not a specific test to diagnose Alzheimer`s disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity.

Fibromyalgia in primary antiphospholipid (Hughes) syndrome

Fibromyalgia (FM) is a syndrome that can be associated with several rheumatic diseases. However, no study has evaluated its frequency in patients with primary antiphospholipid syndrome (PAPS). The objective of this study was to analyze the frequency of FM in PAPS patients compared with healthy controls, to determine the possible associations between FM and PAPS features, and also to evaluate quality of life and depression in these patients. This case-control study included 30 PAPS patients (by the Sapporo criteria) and 40 healthy subjects. Demographic and clinical data, drug use, and antiphospholipid antibodies were analyzed. FM was diagnosed based on international criteria (ACR). Questionnaires on quality of life, including the Short Form 36 Health Survey (SF-36), Beck Depression Inventory (BDI), Fibromyalgia Impact Questionnaire (FIQ), and Visual Analog Scale (VAS), were also applied. PAPS patients and controls were similar in mean age as well as in distributions of gender and Caucasian race. Mean disease duration was 5.4 +/- 4.2 years. A diagnosis of fibromyalgia was made in five (16.7%) PAPS patients and no controls (p = 0.012). PAPS patients had more diffuse pain (53% vs. 0%, respectively, p<0.0001), >= 11 tender points (23% vs. 5%, respectively, p = 0.032), and a greater total number (175 vs. 57, respectively, p<0.0001) as well as median number of tender points per patient than controls (5 [0-18] vs. 0 [0-11], respectively, p<0.0001). PAPS patients had lower values in all dimensions of the SF-36, as well as higher FIQ scores, higher BDI scores, more depression diagnoses according to BDI results, and increased VAS in comparison with controls. Analysis of PAPS patients with FM compared with those subjects without FM revealed no significant differences regarding demographic features or thrombotic or clinical events; however, PAPS patients who also had FM had lower values in SF-36 dimensions as well as higher FIQ (82.6 +/- 9.6 vs. 33.6 +/- 29.8, respectively, p<0.0001) and VAS scores (6.6 +/- 2.97 vs. 3.25 +/- 3.11, respectively, p = 0.03). BDI scores, in contrast, were similar in both groups. In conclusion, one-fifth of PAPS patients had fibromyalgia and a low quality of life when compared with healthy subjects. Lupus (2011) 20, 1182-1186.

Alcohol use disorders in patients with obsessive-compulsive disorder: The importance of appropriate dual-diagnosis

Objective: To evaluate the prevalence and clinical associated factors of alcohol use disorders (AUD) comorbidity in a large clinical sample of patients with obsessive-compulsive disorder (OCD). Methods: A cross-sectional study including 630 DSM-IV OCD patients from seven Brazilian university services, comparing patients with and without AUD comorbidity. The instruments of assessment used were a demographic and clinical questionnaire including evaluation of suicidal thoughts and acts and psychiatric treatment, the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I), the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Beck Depression and Anxiety Inventories and the Clinical Global Impression Scale. Current or past alcohol and other psychoactive substances use, abuse and dependence were assessed using the SCID-I (section E) and corroborated by medical and familial history questionnaires. Results: Forty-seven patients (7.5%) presented AUD comorbidity. Compared to OCD patients without this comorbidity they were more likely to be men, to have received previous psychiatric treatment, to present: lifetime suicidal thoughts and attempts and to have higher scores in the hoarding dimension. They also presented higher comorbidity with generalized anxiety and somatization disorders, and compulsive sexual behavior. Substance use was related to the appearance of the first O.C. symptoms and symptom amelioration. Conclusions: Although uncommon among OCD treatment seeking samples, AUD comorbidity has specific clinical features, such as increased risk for suicidality, which deserve special attention from mental health professionals. Future studies focused on the development of specific interventions for these patients are warranted. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The Use of Smell Identification Tests in the Diagnosis of Parkinson`s Disease in Brazil

Smell identification tests may be of routine clinical value in the differential diagnosis of PD but are subject to cultural variation and have not been systematically evaluated in the Brazilian population. We have applied culturally adapted translations of the University of Pennsylvania 40-item smell identification test (UPSIT-40) and the 16-item identification test from Sniffin` Sticks (SS-16) to nondemented Brazilian PD patients and controls. Pearson`s correlation coefficient between the test scores was 0.76 (95% CI 0.70-0.81, n = 204, P < 0.001). To calculate reliability measures for each test we used the diagnosis (either PD or control) as outcome variable for separate logistic regression analyses using the score in the UPSIT-40 or the SS-16 as a covariate. The SS-16 specificity was 89.0% with a sensitivity of 81.1% (106 PD and 118 controls). The UPSIT-40 specificity was 83.5% and its sensitivity 82.1% (95 PD and 109 controls). Regression curves were used to associate an individual`s smell test score with the probability of belonging to the PD, as opposed to the control group. Our data provide support for the use of the UPSIT-40 and SS-16 to help distinguish early PD from controls. (c) 2008 Movement Disorder Society

Primary antiphospholipid syndrome with and without Sneddon`s syndrome

The main objective of this study was to compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (PAPS) with and without Sneddon`s syndrome (SS). A transverse study with 54 (85.2% female) PAPS patients (Sapporo criteria) was performed. Demographic, drug use, and antiphospholipid antibodies data were evaluated, as well as clinical and laboratory findings of SS. Patients were subdivided into one of two groups: PAPS with SS and PAPS without SS. Both groups were similar with respect to age (p = 0.05), gender (p = 0.34), race (p = 0.31), weight (p = 0.93), height (p = 0.27), and body mass index (p = 0.75); however, the SS group exhibited higher disease duration (96.0 +/- A 54.9 vs. 55.2 +/- A 52.0 months, p = 0.01). By definition, all PAPS with SS patients suffer from stroke, an arterial event; the frequency of stroke events (28.5 vs. 7.5%, p = 0.04), as well as of limb ischemia (100 vs. 30.0%, p < 0.0001) was higher in this group than in the PAPS without SS group. On the other hand, patients in the PAPS without SS group had more venous events, such as deep venous thrombosis, than those in the PAPS with SS group (80.0 vs. 50.0%, p = 0.03). In conclusion, an understanding of the relationship between APS and SS is important in order to identify a subgroup for which more rigorous accompaniment and therapy may be necessary.

Transsphenoidal meningoencephalocele associated with cleft lip and palate: challenges for diagnosis and surgical treatment

The aim of this study was to highlight the challenges for early diagnosis and the difficulties observed in surgical treatment of patients with transsphenoidal meningoencephalocele associated with cleft lip and/or palate. We evaluated six male patients treated over the course of 4 years. Five patients presented encephalic herniation with nonfunctional brain tissue; one of these presented herniation of the pituitary gland and cerebral ventricles. All the patients received surgical treatment for the cleft lip and/or palate. Only one patient underwent repair of the meningoencephalocele, via nasal endoscopy. There were no postprocedural clinical or surgical complications. The tendency is to avoid neurosurgery, opting for periodic follow-up with magnetic resonance imaging. In the presence of cleft palate, palatoplasty is essential to protect the meningoencephalocele.

The Role of Prostate Specific Membrane Antigen and Pepsinogen C Tissue Expression as an Adjunctive Method to Prostate Cancer Diagnosis

Purpose: The diagnosis of prostate cancer in men with persistently increased prostate specific antigen after a negative prostate biopsy has become a great challenge for urologists and pathologists. We analyzed the diagnostic value of 6 genes in the tissue of patients with prostate cancer. Materials and Methods: The study was comprised of 50 patients with localized disease who underwent radical prostatectomy. Gene selection was based on a previous microarray analysis. Among 4,147 genes with different expressions between 2 pools of patients 6 genes (PSMA, TMEFF2, GREB1, TH1L, IgH3 and PGC) were selected. These genes were tested for diagnostic value using the quantitative reverse transcription polymerase chain reaction method. Initially malignant tissue samples from 33 patients were analyzed and in the second part of the study we analyzed benign tissue samples from the other 17 patients with prostate cancer. The control group was comprised of tissue samples of patients with benign prostatic hyperplasia. Results: Analysis of malignant prostatic tissue demonstrated that prostate specific membrane antigen was over expressed (mean 9 times) and pepsinogen C was under expressed (mean 1.3 X 10(-4) times) in all cases compared to benign prostatic hyperplasia. The other 4 tested genes showed a variable expression pattern not allowing for differentiation between benign and malignant cases. When we tested these results in the benign prostate tissues from patients with cancer, pepsinogen C maintained the expression pattern. In terms of prostate specific membrane antigen, despite over expression in most cases (mean 12 times), 2 cases (12%) presented with under expression. Conclusions: Pepsinogen C tissue expression may constitute a powerful adjunctive method to prostate biopsy in the diagnosis of prostate cancer cases.