Prostatic paracoccidioidomycosis: differential diagnosis of prostate cancer

Symptomatic prostatic paracoccidioidomycosis (PCM) is a very rare condition; however, it may express as a typical benign prostatic hyperplasia or a simulating prostatic adenocarcinoma. This case report presents PCM mimicking prostatic adenocarcinoma. The purpose of this paper is to call the general physician's attention to this important differential diagnosis.

Lesion aspirate culture for the diagnosis and isolation of Leishmania spp. from patients with cutaneous leishmaniasis

The detection of Leishmania spp. in skin lesion aspirates, using a puncture technique, was evaluated in 76 patients with cutaneous leishmaniasis (CL) who were referred to a Leishmaniasis Reference Centre in Brazil. CL was defined based on skin lesions suggestive of the disease and on a positive result of the Montenegro skin test or Giemsa-stained imprints of biopsy fragments. The aspirates were cultured using a vacuum tube device containing culture medium and evaluated for the presence of Leishmania spp. The biphasic medium culture was examined once a week for three weeks. Promastigotes were observed in 53/76 (69.7%) cultures. Stained smears from 60 of the 76 patients were evaluated using PCR-RFLP to detect the conserved minicircle region of Leishmania spp. and to classify the parasite. Of these patients, 45 (75%) showed positive results in aspirate culture and 15 presented negative results. The PCR was positive in 80% (53/60) samples. The PCR-RFLP profile was determined in 49 samples, of which 45 (92%) showed a pattern compatible with Leishmania (Viannia) braziliensis. The aspirate culture is a sensitive and feasible method for diagnosing CL and may be routinely adopted by health services for L. (V.) braziliensis isolation and identification.

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.

Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosis

The aim of this study was to determine the incidence of congenital toxoplasmosis (CT) and to assess the performances of prenatal and neonatal diagnoses. From 1994-2005, in Toulouse University Hospital, France, amniocentesis was performed on 352 pregnant women who were infected during pregnancy. All women were treated with spiramycin and pyrimethamine-sulfadoxine when prenatal diagnosis was positive. Among the 275 foetuses with follow-up, 66 (24%) were infected. The transmission rates of Toxoplasma gondii were 7%, 24% and 59% in the first, second and third trimesters, respectively. The sensitivity and specificity of PCR on amniotic fluid (AF) were 91% and 99.5%, respectively. One case was diagnosed by mouse inoculation with AF and six cases were diagnosed by neonatal or postnatal screening. The sensitivity and specificity of PCR on placentas were 52% and 99%, respectively. The sensitivity of tests for the detection of specific IgA and IgM in cord blood was 53% and 64%, respectively, and specificity values were 91% and 92%. In conclusion, PCR performed on AF had the highest levels of sensitivity and specificity for the diagnosis of CT. This permits an early diagnosis of most cases and should be recommended.

A simple approach improving the performance of urine reagent strips for rapid diagnosis of urinary schistosomiasis in Nigerian schoolchildren

In Nigeria, schistosomiasis, caused predominantly by the species Schistosoma haematobium, is highly endemic in resource-poor communities. We performed a school-based survey in two rural communities in Osun State (Southwestern Nigeria) and assessed macrohaematuria, microhaematuria and proteinuria as indirect indicators for the presence of disease. Urine samples were inspected macroscopically for haematuria and screened for microhaematuria and proteinuria using urine reagent strips. The microscopic examination of schistosome eggs was used as the gold standard for diagnosis. In total, 447 schoolchildren were included in this study and had a 51% prevalence of urinary schistosomiasis. The sensitivity of microhaematuria (68%) and proteinuria (53%) for infection with S. haematobium was relatively low. In patients with a heavy infection (>500 eggs/10 mL), the sensitivity of microhaematuria was high (95%). When the presence of macrohaematuria and the concomitant presence of microhaematuria and proteinuria were combined, it revealed a sensitivity of 63%, a specificity of 93% and a positive predictive value of 91%. Macrohaematuria also showed high specificity (96%) and a positive predictive value of 92%, while sensitivity was < 50%. These data show that combining urine reagent strip tests (presence of proteinuria and microhaematuria) and information on macrohaematuria increased the accuracy of the rapid diagnosis of urinary schistosomiasis in an endemic rural West African setting. This simple approach can be used to increase the quality of monitoring of schistosomiasis in schoolchildren.

Le myélome à chaînes légères ou les pièges du diagnostic du myélome [Light chain myeloma or the pitfalls of myeloma diagnosis]

The diagnosis of multiple myeloma is often suggested by disturbances found in routine laboratory tests such as sedimentation rate, electrophoresis of serum proteins and search for proteinuria. In light chain myeloma these tests are nonspecific and therefore misleading. We present 8 cases of light chain myeloma and discuss the diagnosis of multiple myeloma with its associated pitfalls.

Comparison of tests for the detection of circulating filarial antigen (Og4C3-ELISA and AD12-ICT) and ultrasound in diagnosis of lymphatic filariasis in individuals with microfilariae

Significant advances were made in the diagnosis of filariasis in the 1990s with the emergence of three new alternative tools: ultrasound and tests to detect circulating antigen using two monoclonal antibodies, Og4C3 and AD12-ICT-card. This study aimed to identify which of these methods is the most sensitive for diagnosis of infection. A total of 256 individuals, all male and carrying microfilariae (1-15,679 MF/mL), diagnosed by nocturnal venous blood samples, were tested by all three techniques. The tests for circulating filarial antigen concurred 100% and correctly identified 246/256 (96.69%) of the positive individuals, while ultrasound detected only 186/256 (73.44%). Of the circulating antigen tests, ICT-card was the most convenient method for identification of Wuchereria bancrofti carriers. It was easy to perform, practical and quick.

Use of a saline gradient for the diagnosis of schistosomiasis

The development of novel methods for parasitological diagnosis that are both highly sensitive and low in cost has been strongly recommended by the World Health Organization. In this study, a new technique for diagnosis of schistosomiasis mansoni is proposed based on the differential sedimentation of eggs when subjected to a slow continuous flux of 3% saline solution through a porous plaque. This influx suspends low-density faecal material, effectively cleaning the sample. The remaining sediment covering the porous plaque surface is then transferred to a glass slide and examined under a bright field microscope. Twelve Kato-Katz slides were used for comparison in the present study. Our results suggest that the saline gradient method detects a signifi-cantly higher number of eggs than the 12 Kato-Katz slides (p < 0.0001). We also found microscopic inspection to be quicker and easier with our newly described method. After cleaning the sample, the obtained sediment can also be conserved in a 10% formaldehyde solution and examined for at least 45 days later without statistically significant egg count differences.

Consensus statement of the European guidelines on clinical management of HIV-1 tropism testing

Introduction: Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. To date, in most European countries HIV tropism is determined using a phenotypic test. Recently, new data have emerged supporting the use of a genotypic HIV V3-loop sequence analysis as the basis for tropism determination. The European guidelines group on clinical management of HIV-1 tropism testing was established to make recommendations to clinicians and virologists. Methods: We searched online databases for articles from Jan 2006 until March 2010 with the terms: tropism or CCR5-antagonist or CCR5 antagonist or maraviroc or vicriviroc. Additional articles and/or conference abstracts were identified by hand searching. This strategy identified 712 potential articles and 1240 abstracts. All were reviewed and finally 57 papers and 42 abstracts were included and used by the panel to reach a consensus statement. Results: The panel recommends HIV-tropism testing for the following indications: i) drug-naïve patients in whom toxicity or limited therapeutic options are foreseen; ii) patients experiencing therapy failure whenever a treatment change is considered. Both the phenotypic Enhanced Trofile assay (ESTA) and genotypic population sequencing of the V3-loop are recommended for use in clinical practice. Although the panel does not recommend one methodology over another it is anticipated that genotypic testing will be used more frequently because of its greater accessibility, lower cost and shorter turnaround time. The panel also provides guidance on technical aspects and interpretation issues. If using genotypic methods, triplicate PCR amplification and sequencing testing is advised using the G2P interpretation tool (clonal model) with an FPR of 10%. If the viral load is below the level of reliable amplification, proviral DNA can be used, and the panel recommends performing triplicate testing and use of an FPR of 10%. If genotypic DNA testing is not performed in triplicate the FPR should be increased to 20%. Conclusions: The European guidelines on clinical management of HIV-1 tropism testing provide an overview of current literature, evidence-based recommendations for the clinical use of tropism testing and expert guidance on unresolved issues and current developments. Current data support both the use of genotypic population sequencing and ESTA for co-receptor tropism determination. For practical reasons genotypic population sequencing is the preferred method in Europe.

Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis

Background: Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status of Estrogen Receptor1 (ESR1) and Stratifin (14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients. Methods: We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. Results: Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the "continuous decline" and "rise-and-fall" groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0.074) indicates that this test is a good approach to post-treatment prognosis. Conclusions: The relationship of 14-3-3-σ with breast cancer metastasis and progression found in this study suggests a possible application of 14-3-3-σ as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.

Serological diagnosis of Chagas disease: evaluation and characterisation of a low cost antigen with high sensitivity and specificity

In spite of evident progress in the serology of Chagas disease, the requirement for new diagnostic antigens persists. We have evaluated different antigens obtained from Trypanosoma cruzi grown in medium rich in nutrients or under nutrient stress, autoclaved or sonicated and fractionated by differential centrifugation. The resulting antigens were evaluated for diagnosis of Chagas disease using ELISA. Immunofluorescence of the parasites demonstrated that nutrient stress induced changes in the distribution and density of antigens recognised by a pool of sera from experimentally infected mice. When evaluated using ELISA, it was evident that most fractions had good sensitivity but poor specificity. Surprisingly, the best specificity and sensitivity was observed with parasites cultured under nutrient stress and autoclaved. Furthermore this antigen had low cross reactivity with sera from other parasitic diseases, Leishmaniasis in particular. Western blot analysis demonstrated that autoclaving seems to non-specifically eliminate cross-reactive antigens. In conclusion, autoclaving epimastigotes of T. cruzi, after nutrient stress, allowed us to obtain an antigen that could be used in the serological diagnosis of Chagas disease.

Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil

The positivities of two methods for the diagnosis of localised cutaneous leishmaniasis (CL) were estimated in 280 patients enrolled in a clinical trial. The trial was conducted in an endemic area of Leishmania (Viannia) braziliensis and trial participants were patients with skin ulcers and positive leishmanin skin tests. Patients underwent aspirative skin punctures of the ulcerated lesions and lymph nodes for in vitro cultures, which were processed under field conditions at the local health centre. Skin lesion biopsies were tested at a reference laboratory using kinetoplastid DNA (kDNA)-PCR to detect DNA. The median time required to obtain a positive culture from the skin samples was seven days and the contamination rate of the samples was 1.8%. The positivities of the cultures from skin lesions, kDNA-PCR and the combination of the two methods were 78.2% (95% CI: 73-82.6%), 89.3% (95% CI: 85.1-92.4%) and 97.1% (95% CI: 94.5-98.5%). We conclude that parasite culture is a feasible method for the detection of Leishmania in field conditions and that the combination of culture and PCR has a potential role for the diagnosis of CL in candidates for clinical trials.

Extranodal NK/T-Cell Lymphoma without Nasal Cavity Involvement Associated with Epstein-Barr Virus:AMultimodality-Based Diagnosis of Two Cases

We report two cases of extranodal NK/T-cell lymphoma, nasal type, in immunocompetent patients without nasal cavity involvement. In the two cases, the initial presumptive diagnosis was tuberculosis and there was a rapid dissemination of the tumor with short survival after the hospital admittance. An autopsy was performed showing infiltration in several organs including lymph nodes and mesenteric and retroperitoneal fat. Histological sections showed an angiocentric and angiodestructive growth pattern and the immunophenotype was CD45+, CD3+ (cytoplasmic), as well as Granzyme B+ and EBV+. However, CD56 expression was only positive in a case in which the molecular study showed T-cell gene rearrangement with monoclonal appearance and associated with hemophagocytic syndrome. These cases represent rare examples of NK/T-cell lymphoma disseminated outside the nasal cavity highly aggressive that lead to the rapid death of the patients.

Fistulizing Crohn's disease: Diagnosis and management.

Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.

Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique 4 questions) questionnaire for differential diagnosis of pain syndromes associated to a neuropathic or somatic component

BACKGROUND This study assesses the validity and reliability of the Spanish version of DN4 questionnaire as a tool for differential diagnosis of pain syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic pain, NNP). METHODS A study was conducted consisting of two phases: cultural adaptation into the Spanish language by means of conceptual equivalence, including forward and backward translations in duplicate and cognitive debriefing, and testing of psychometric properties in patients with NP (peripheral, central and mixed) and NNP. The analysis of psychometric properties included reliability (internal consistency, inter-rater agreement and test-retest reliability) and validity (ROC curve analysis, agreement with the reference diagnosis and determination of sensitivity, specificity, and positive and negative predictive values in different subsamples according to type of NP). RESULTS A sample of 164 subjects (99 women, 60.4%; age: 60.4 +/- 16.0 years), 94 (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and 70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71-0.89), and test-retest intra-class correlation coefficient: 0.95 (0.92-0.97)] and valid for a cut-off value > or = 4 points, which was the best value to discriminate between NP and NNP subjects. DISCUSSION This study, representing the first validation of the DN4 questionnaire into another language different than the original, not only supported its high discriminatory value for identification of neuropathic pain, but also provided supplemental psychometric validation (i.e. test-retest reliability, influence of educational level and pain intensity) and showed its validity in mixed pain syndromes.