Prevalence of oral hairy leukoplakia and epithelial infection by Epstein-Barr virus in pregnant women and diabetes mellitus patients: cytopathologic and molecular study

Oral hairy leukoplakia (OHL) is generally reported in patients with severe immunosuppression, except for a few cases in individuals with moderate degree of immunodeficiency. It is a white lesion that appears mainly in the lateral border of the tongue, caused by Epstein-Barr virus (EBV). The nuclear changes caused by EBV (Cowdry A inclusion, ground glass and nuclear beading), observed in cytopathology, are specific and enough for the definitive diagnosis of OHL, independent of the identification of the virus. Here we investigated the prevalence of OHL and the presence of EBV-DNA in the lateral borders of the tongue from 90 pregnant women, 90 diabetes mellitus (DM) patients, 30 healthy individuals (negative group) and 30 HIV+ with OHL (positive group). Smears were analyzed by cytopathology and polymerase chain reaction (PCR). A case of subclinical OHL and candidiasis was identificated in a DM patient by cytopathologic analysis. PCR results demonstrated EBV-DNA in 65% of the pregnant women, in 35% of DM patients, and in 20% of the healthy individuals. We concluded that DM patients can develop OHL with a low prevalence. Furthermore, the prevalence of the EBV in lateral border of the tongue is larger in pregnant women than in healthy individuals.

Polymerase chain reaction genotyping of Epstein-Barr virus in scraping samples of the tongue lateral border in HIV-1 seropositive patients

The Epstein-Barr virus (EBV) is the etiological agent of oral hairy leukoplakia (OHL), an oral lesion with important diagnostic and prognostic value in acquired immunodeficiency disease syndrome. The two EBV genotypes, EBV-1 and EBV-2, can be distinguished by divergent gene sequences encoding the EBNA-2, 3A, 3B, and 3C proteins. The purpose of this study was to identify the EBV genotype prevalent in 53 samples of scrapings from the lateral border of the tongue of HIV-1 seropositive patients, with and without OHL, and to correlate the genotypes with presence of clinical or subclinical OHL with the clinic data collected. EBV-1 and EBV-2 were identified through PCR and Nested-PCR based on sequence differences of the EBNA-2 gene. EBV-1 was identified in the 31 samples (15 without OHL, 7 with clinical OHL and 9 with subclinical OHL), EBV-2 in 12 samples (10 without OHL, 1 with clinical and 1 subclinical OHL), and a mixed infection in 10 samples (2 without OHL, 3 with clinical and 5 with subclinical OHL). The presence of EBV-1 was higher in women, but a significant statistical result relating one the EBV genotypes to the development of OHL was not found. We conclude that the oral epithelium in HIV-1 seropositive patients can be infected by EBV-1, EBV-2 or by a mixed viral population.

Acute retinal necrosis in primary herpes simplex virus type I infection.

Here we report the case of an immunocompetent 8-year-old child who developed acute retinal necrosis concomitant with a primary herpes simplex virus type I infection. Ocular inflammation changed along with the development of a specific antibody titer in the serum. This evidence suggests that the immune response of the host can significantly modulate the clinical aspect of the ocular infection.

Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension].

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

Pathophysiology and classification of the vibration white finger.

Skin, arteries and nerves of the upper extremities can be affected by vibration exposure. Recent advances in skin and vascular biology as well as new investigative methods, have shown that neurovascular symptoms may be due to different vascular and neurological disorders which should be differentiated if proper management is to be evaluated. Three types of vascular disorder can be observed in the vibration white finger: digital organic microangiopathy, a digital vasospastic phenomenon and arterial thrombosis in the upper extremities. An imbalance between endothelin-1 and calcitonin-gene-related peptide is probably responsible for the vasospastic phenomenon. Moreover, paresthesiae can be due to either a diffuse vibration neuropathy or a carpal tunnel syndrome. A precise diagnosis is then necessary to adapt the treatment to individual cases. A classification describing the type and severity of the vascular lesions is presented. Asymptomatic lesions are included for adequate epidemiological studies and risk assessment of vibrating tools. Monitoring of vibration exposed workers should include not only a questionnaire about symptoms, but also a clinical evaluation including diagnostic tests for the screening of early asymptomatic neurovascular injuries.

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.

Indocyanine Green Angiography Findings in Acute Retinal Necrosis Syndrome.

BACKGROUND: Acute retinal necrosis syndrome is clinically defined by the presence of peripheral necrotizing retinitis associated with severe occlusive vasculitis caused primarily by herpes simplex virus and varicella zoster virus. Previously considered as an exclusively retinal pathology, choroidal involvement, as demonstrated by indocyanine green angiography, has not been extensively studied. HISTORY AND SIGNS: Indocyanine green angiography was performed in 4 patients with ARN. Observed angiographic patterns included: 1. a characteristic triangular area of hypo-perfusion, 2. hypofluorescent lobular patches and areas of fuzzy choroidal vascular hyperfluorescence, and 3. isolated hypofluorescent lobular patches of the contralateral eye. THERAPY AND OUTCOME: Marked choroidal hypo-perfusion on indocyanine green angiography was associated with extensive retinal ischemia. Treatment included a combination of antiviral agents and corticosteroids complemented by prophylactic acetylsalicylate. CONCLUSION: Indocyanine green angiography may provide important information regarding choroidal vascular involvement in ARN. It may also permit the timely identification of sub-clinical contralateral eye involvement.

Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.

Molecular characterisation of dengue virus type 1 reveals lineage replacement during circulation in Brazilian territory

Dengue fever is the most important arbovirus infection found in tropical regions around the world. Dispersal of the vector and an increase in migratory flow between countries have led to large epidemics and severe clinical outcomes, such as dengue haemorrhagic fever and dengue shock syndrome. This study analysed the genetic variability of the dengue virus serotype 1 (DENV-1) in Brazil with regard to the full-length structural genes C/prM/M/E among 34 strains isolated during epidemics that occurred in the country between 1994-2011. Virus phylogeny and time of divergence were also evaluated with only the E gene of the strains isolated from 1994-2008. An analysis of amino acid differences between these strains and the French Guiana strain (FGA/89) revealed the presence of important nonsynonymous substitutions in the amino acid sequences, including residues E297 (Met→Thr) and E338 (Ser→Leu). A phylogenetic analysis of E proteins comparing the studied isolates and other strains selected from the GenBank database showed that the Brazilian DENV-1 strains since 1982 belonged to genotype V. This analysis also showed that different introductions of strains from the 1990s represented lineage replacement, with the identification of three lineages that cluster all isolates from the Americas. An analysis of the divergence time of DENV-1 indicated that the lineage circulating in Brazil emerged from an ancestral lineage that originated approximately 44.35 years ago.

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4+ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4+ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8+ and human leukocyte antigen-DR expression on CD3+ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.

Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

First report of autochthonous transmission of Zika virus in Brazil

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.

Zika virus damages the human placental barrier and presents marked fetal neurotropism

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model

The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evidences was also quantified by TaqMan low-density arrays. Our results showed enrichment in deregulated genes involved in cell death, cell morphology and cancer as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expression profile along with the phenotype led us to conclude that anx/anx mice resemble the anorexia-cachexia syndrome typically observed in cancer, infection with human immunodeficiency virus or chronic diseases, rather than starvation, and that anx/anx mice could be considered a good model for the treatment and investigation of this condition.

Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study.

BACKGROUND: Recent data suggest that varicella zoster virus (VZV)-associated complications of the central nervous system (CNS) are more common and diverse than previously thought. The main purpose of this article is to describe the clinical characteristics and the outcome of patients suffering from meningitis and encephalitis caused by VZV reactivation. METHODS: A retrospective case study of adult patients (≥16 years old) diagnosed with a VZV reactivation in the CNS was performed. The cases were identified by a qualitative PCR DNA assay of the cerebrospinal fluid (CSF) at the Regional Hospital of Lugano between January 1, 2003 and July 31, 2010. RESULTS: Eleven out of 519 CSF samples (2.1%), submitted from patients with a clinical diagnosis of viral meningitis or encephalitis, were positive for VZV. A vesiculo-pustular skin eruption was observed in only five patients (45%). In six cases (55%), a systemic inflammatory syndrome was absent. The clinical outcome was favorable in eight patients (73%). Only one out of 11 patients (9%) died. The four patients with encephalitis had a less favorable prognosis: one patient recovered without residual neurological sequelae; two had a chronic neuropsychological handicap, speech difficulties, facial nerve palsy, and focal seizures; one patient died. We estimated an annual incidence rate of VZV infection of the CNS of 1.02/100 000 inhabitants for southern Switzerland. CONCLUSIONS: Screening of CSF for VZV by PCR is recommended for all patients with encephalitis and for those with viral meningitis of unclear origin in order to better target antiviral treatment.