Mast cell-associated alveolar inflammation in patients with atopic uncontrolled asthma

Background: A significant proportion of patients with asthma have persistent symptoms despite treatment with inhaled glucocorticosteroids. Objective: We hypothesized that in these patients, the alveolar parenchyma is subjected to mast cell-associated alterations. Methods: Bronchial and transbronchial biopsies from healthy controls (n = 8), patients with allergic rhinitis (n = 8), and patients with atopic uncontrolled asthma (symptoms despite treatment with inhaled glucocorticosteroids; mean dose, 743 mu g/d; n = 14) were processed for immunohistochemical identification of mast cell subtypes and mast cell expression of Fc epsilon RI and surface-bound IgE. Results: Whereas no difference in density of total bronchial mast cells was observed between patients with asthma and healthy controls, the total alveolar mast cell density was increased in the patients with asthma (P < .01). Division into mast cell subtypes revealed that in bronchi of patients with asthma, tryptase positive mast cells (MC(T)) numbers decreased compared with controls (P <= .05), whereas tryptase and chymase positive mast cells (MC(TC)) increased (P <= .05). In the alveolar parenchyma from patients with asthma, an increased density was found for both MC(T) (P <= .05) and MC(TC) (P <= .05). The increased alveolar mast cell densities were paralleled by an increased mast cell expression of FceRI (P < .001) compared with the controls. The patients with asthma also had increased numbers (P < .001) and proportions (P < .001) of alveolar mast cells with surface-bound IgE. Similar increases in densities, FceRI expression, and surface-bound IgE were not seen in separate explorations of alveolar mast cells in patients with allergic rhinitis. Conclusion: Our data suggest that patients with atopic uncontrolled asthma have an increased parenchymal infiltration of MCT and MCTC populations with increased expression of FceRI and surface-bound IgE compared with atopic and nonatopic controls. (J Allergy Clin Immunol 2011;127:905-12.)

PLUNC protein expression in major salivary glands of HIV-infected patients

Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non-specific sialadenitis, and 30 HIV-negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV-negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV-negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non-HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.

In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus

The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response. (C) 2011 Elsevier B.V. All rights reserved.

Prevalence and distribution of the GBV-C/HGV among HIV-1-infected patients under anti-retroviral therapy

Infection with GB virus C (GBV-C) or hepatitis G virus (HGV) is highly prevalent among HIV/AIDS patients. GBV-C/HGV viremia has not been associated with liver disease and seems to slow HIV disease progression. To study the GBV-C/HGV genotypes prevalence among HIV/AIDS patients and its association with HIV viral load (VL) and CD4+ lymphocyte counts. From February 2003 to February 2004, we analyzed 210 HIV-1-infected subjects who were on anti-retroviral therapy (ART). For 63 of them a PCR-nested to the non-coding 5` (5`NCR) region of the GBV-C/HGV was done, and for 49 a DNA direct sequencing was done. A phylogenetic analysis was performed by PHYLIP program. 63(30%) of the HIV-1-infected patients were co-infected with GBV-C/HGV. The phylogenetic analysis revealed the following genotypes (and respective relative frequencies): 1(10%), 2a (41%), 2b (43%), and 3 (6%). Co-infected patients presented lower HIV-1 VL and higher T CD4+ lymphocyte cells counts as compared with patients negative for GBV-C/HGV sequences (log = 4.52 vs. 4.71, p = 0.036), and T CD4+ lymphocyte counts (cells/mm(3) = 322.6 vs. 273.5, p = 0.081, respectively). T CD4+ cells counts equal to, or higher than, 200/mm(3) were significantly more common among co-infected patients than among HIV-infected-only patients (p = 0.042). The lowest T CD4+ cells counts were associated with genotype 1 and the highest with genotype 2b (p = 0.05). The GBV-C/HGV infection prevalence was 30% among HIV-1-infected subjects, and was associated with lower VL and higher CD4+ lymphocyte counts. GBV-C/HGV genotype 2b may be associated with better immunological response. Published by Elsevier B.V.

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n = 43) or split vaccine (n = 47) Two blood samples were collected, one before and one 4-6 weeks after vaccination Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test Post-vaccine reactions were recorded over 7 days Seroconversion rates for HI NI, H3N2 and B were 65 1%. 60 4% and 83 7% for virosome vaccine, and 68 0%, 61 7% and 68 0% for split vaccine Seroprotection rates for HI NI, H3N2 e B were 100%. 97 6% and 69.7% for virosome. and 97 8%, 97 8% and 76 6% for split vaccine No severe adverse reactions were recorded Virosome and split vaccines in patients with sickle cell anemia were equally Immunogenic. with high seroconversion and seroprotection rates Both vaccines were well tolerated (C) 2009 Elsevier Ltd All rights reserved

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil

Background Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. Objective and methods The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. Results The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). Conclusion The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Hodgkin`s Lymphoma Presenting as Dominant Gastric Lesion in Immunocompetent Patients: Report of 5 Cases With EBV Analysis

Primary Hodgkin`s lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histological overlap between HLs and some non-HLs or undifferentiated carcinoma, make the surgical resection diagnosis extremely difficult. An accurate diagnosis is important as treatment and outcome differ significantly for these neoplasms. In small endoscopic gastric biopsies and even in postoperative specimens, the precise histological diagnosis of HL is particularly challenging. Here, the authors report 5 cases of 2 women and 3 men aged 22 to 68, with gastric involvement by classic HLs-3 primary gastric HLs and 2 as part of widespread disease. All 5 patients presented with digestive symptoms. At endoscopy, the lesions presented as ulcerated and elevated lesions, with or without mucosal thickening. Four patients were misdiagnosed in the preoperative biopsy or in the gastrectomy specimen. Association with Epstein-Barr virus (EBV) was detected in 4 cases, with a predominance of subtype A EBV. These cases illustrate the significant difficulties, both clinical and pathological, in achieving the diagnosis of HL involving the stomach in immunocompetent patients.

Effect of temporal lobe structure volume on memory in elderly depressed patients

Objective: To compare the volume of the hippocampus and parahippocampal gyrus in elderly individuals with and without depressive disorders, and to determine whether the volumes of these regions correlate with scores on memory tests. Method: Clinical and demographic differences, as well as differences in regional gray matter volumes, were assessed in 48 elderly patients with depressive disorders and 31 control subjects. Brain (structural MRI) scans were processed using statistical parametric mapping and voxel-based morphometry. Cognitive tests were administered to subjects in both groups. Results: There were no between-group gray matter volume differences in the hippocampus or parahippocampal gyrus. In the elderly depressed group only, the volume of the left parahippocampal gyrus correlated with scores on the delayed naming portion of the visual verbal learning test. There were also significant direct correlations in depressed subjects between the volumes of the left hippocampus, right and left parahippocampal gyrus and immediate recall scores on verbal episodic memory tests and visual learning tests. In the control group, there were direct correlations only between overall cognitive performance (as assessed with the MMSE) and the volume of right hippocampus, and between the total score on the visual verbal learning test and the volume of the right and left parahippocampal gyrus. Conclusions: These findings highlight different patterns of relationship between cognitive performance and volumes of medial temporal structures in depressed individuals and healthy elderly subjects. The direct correlation between delayed visual verbal memory recall scores with left parahippocampal volumes specifically in elderly depressed individuals provides support to the view that depression in elderly populations may be a risk factor for dementia. (C) 2009 Elsevier Inc. All rights reserved.

The need for effective radiosentitizing agents: experience in patients with complete pathological response

Chemoradiation therapy is now considered the preferred initial treatment strategy for distal rectal cancer because of the observation of better local disease control and significant tumor downstaging. Downstaging has become an important clinical outcome as patients with complete pathological response are associated with improved survival. Even though radiation alone may result in low local recurrence rates, the use of additional radiosensitizing agents may provide an increase in local disease control in addition to improved tumor regression rates. Several compounds have been investigated in the setting of neoadjuvant multimodality treatment of rectal cancer with variable rates of treatment-related toxicity and complete pathological response. The balance between complete pathological response and toxicity should aid in the management decision for the use of radiosensitizing agents in the neoadjuvant setting for the treatment of rectal cancer. Anti-Cancer Drugs 22: 308-310 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Can the CAMCOG be a good cognitive test for patients with Alzheimer`s disease with low levels of education?

Background: The Cambridge Cognitive Examination (CAMCOG) is a useful test in screening for Alzheimer`s disease (AD). However, the interpretation of CAMCOG cut-off scores is problematic and reference values are needed for different educational strata. Given the importance of earlier diagnoses of mild dementia, new cut-off values are required which take into account patients with low levels of education. This study aims to evaluate whether the CAMCOG can be used as an accurate screening test among AD patients and normal controls with different educational levels. Methods: Cross-sectional assessment was undertaken of 113 AD and 208 elderly controls with heterogeneous educational levels (group 1: 1-4 years; group 2: 5-8 years; and group 3: >= 9 years) from a geriatric clinic. submitted to a thorough diagnostic evaluation for AD including the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Controls had no cognitive or mood complaints. Sensitivity (SE) and specificity (SP) for the CAMCOG in each educational group was assessed with receiver-operator-characteristic (ROC) curves. Results: CAMCOG mean values were lower when education was reduced in both diagnostic groups (controls - group 1: 87; group 2: 91; group 3: 96; AD - group 1: 63; group 2: 62; group 3: 77). Cutoff scores for the three education groups were 79, 80 and 90, respectively. SE and SP varied among the groups (group 1: 88.1% and 83.5%; group 2: 84.6% and 96%; group 3: 70.8% and 90%). Conclusion: The CAMCOG can be used as a cognitive test for patients with low educational level with good accuracy. Patients with higher education showed lower scores than previously reported.

Pain Relief and Functional Recovery in Patients with Complex Regional Pain Syndrome after Motor Cortex Stimulation

In addition to pain and neurovegetative symptoms, patients with severe forms of complex regional pain syndrome (CRPS) develop a broad range of symptoms, including sensory disturbances, motor impairment and dystonic posturing. While most patients respond to medical therapy, some are considered refractory and become surgical candidates. To date, the most commonly used surgical procedure for CRPS has been spinal cord stimulation. This therapy often leads to important analgesic effects, but no sensory or motor improvements. We report on 2 patients with pain related to CRPS and severe functional deficits treated with motor cortex stimulation (MCS) who not only had significant analgesic effects, but also improvements in sensory and motor symptoms. In the long term (27 and 36 months after surgery), visual analog scale pain scores were improved by 60-70% as compared to baseline. There was also a significant increase in the range of motion in the joints of the affected limbs and an improvement in allodynia, hyperpathia and hypoesthesia. Positron emission tomography scan in both subjects revealed that MCS influenced regions involved in the circuitry of pain. Copyright (C) 2011 S. Karger AG, Basel

Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high-potency nitrogen-containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Paget`s disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.

Assessment of psychosocial adjustment in patients with temporal lobe epilepsy using a standard measure

Despite the growing evidence of poor psychosocial adjustment, at present there is no formal method of assessment of social adjustment in patients with temporal lobe epilepsy (TLE). First, we assessed social adjustment in patients with TLE using a self-report questionnaire and compared the results with those from quality-of-life (QOL) scales. Second, we verified the influence of cognitive performance and clinical variables of epilepsy on social adjustment and QOL We evaluated 35 people with TLE and 38 healthy controls. Patients had worse social adjustment, and it was correlated with worse perception of cognitive function. Attention and verbal memory dysfunctions were negatively correlated with social adjustment. However, there was no significant correlation between cognitive performance and QOL Regarding clinical variables, persons with left TLE showed worse social adjustment and patients with frequent seizures showed worse QOL These findings indicate the relevance of evaluating social adjustment and emphasize the importance of cognitive rehabilitation to improved social adjustment. (c) 2010 Elsevier Inc. All rights reserved.

Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer`s disease, Huntington`s disease and Parkinson`s disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.