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Biomedical subjects

M L Villa

Publications and source records attributed to M L Villa.

At least 19 recordsLinked to original sources

The Frontal Assessment Battery (FAB): normative values in an Italian population sample.

The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six-subtest battery for the bedside screening of a global executive dysfunction; although recently devised, it is already extensively used thanks to its ease of administration and claimed sensitivity. The aim of the present study was to derive Italian normative values from a sample of 364 control subjects (215 women and 149 men) of different ages (mean: 57.4+/-17.9 years; range: 20-94 years) and educational level (mean: 10.4+/-4.3 years; range: 1-17 years); the Mini Mental State Examination (MMSE) was concurrently administered. Multiple linear regression analysis revealed significant effects for age and education whereas gender was not significant; thus, from the derived linear equation, a correction grid for FAB raw scores was built. Based on nonparametric techniques, inferential cut-off scores were subsequently determined and equivalent scores (ES) computed. Test-restest and interrater reliabilities were both satisfactory. Interestingly, MMSE was significantly correlated with FAB raw scores, whereas adjusted scores were not. The present data may improve the accuracy in the use of the FAB both for clinical and research purposes.

Adult↗

Ineffectiveness of an Italian NART-equivalent for the estimation of verbal learning ability in normal elderly.

Comparison between current and premorbid memory ability may be of help when trying to make a timely diagnosis of cognitive decline in questionable dementia. In the present study, we evaluated the possibility of estimating episodic verbal memory scores at the Rey Auditory Verbal Learning Test (RAVLT) from an irregular words reading task held to resist to deterioration, that is the Italian analogue of the NART, the TIB (Test d'Intelligenza Breve--brief intelligence test). A regression analysis was performed in a large sample of healthy elderly, using RAVLT scores as dependent variable and TIB score, MMSE score, age and education as predictors. We failed to find a relationship between the two tests that was strong enough for a reliable estimation of memory ability.

Aged↗

Altered maturation of peripheral blood dendritic cells in patients with breast cancer.

Tumours have at least two mechanisms that can alter dendritic cell (DC) maturation and function. The first affects the ability of haematopoietic progenitors to differentiate into functional DCs; the second affects their differentiation from CD14+ monocytes, promoting an early but dysfunctional maturation. The aim of this study was to evaluate the in vivo relevance of these pathways in breast cancer patients. For this purpose, 53 patients with invasive breast cancer were compared to 68 healthy controls. To avoid isolation or culture procedures for enrichment of DCs, analyses were directly performed by flow cytometry on whole-blood samples. The expression of surface antigens and intracellular accumulation of regulatory cytokines upon LPS stimulation were evaluated. The number of DCs, and in particular of the myeloid subpopulation, was markedly reduced in cancer patients (P<0.001). Patient DCs were characterized by a more mature phenotype compared with controls (P=0.016), and had impaired production of IL-12 (P<0.001). These alterations were reverted by surgical resection of the tumour. To investigate the possible role of some tumour-related immunoactive soluble factors, we measured the plasmatic levels of vascular endothelial growth factor, IL-10 and spermine. A significant inverse correlation between spermine concentration and the percentage of DCs expressing IL-12 was found. Evidence was also obtained that in vitro exposure of monocyte-derived DCs to spermine promoted their activation and maturation, and impaired their function. Taken together, our results suggest that both the above-described mechanisms could concomitantly act in breast cancer to affect DC differentiation, and that spermine could be a mediator of dysfunctional maturation of DCs.

Adult↗

Cognitive [correction of cognitve] estimation: comparison of two tests in nondemented parkinsonian patients.

The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task (CET) are two recently devised tests for the assessment of cognitive estimation. In the present study, we compared their performance in 30 non-demented idiopathic parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery (FAB) as an index of executive impairment, with the aim of verifying the putative frontal circuitry of cognitive estimation processes. Six patients (20%) showed a pathological performance on either or both tests. After division of the PD sample into tertiles based on the FAB score, no significant difference was detected by either estimation test. Furthermore, the two questionnaires were unrelated to each other. Thus, deficits of cognitive estimation ability appear to be mild in PD without dementia and do not correlate with executive impairment. Unexpectedly, the CET and the STEP seem to have no unique underlying construct.

Aged↗

Assessing clinically relevant cognitive decline: preliminary data on a new method.

Physiological age-related cognitive decline, practice effect and regression to the mean may interfere with the interpretation of psychometric changes between subsequent neuropsychological evaluations. The standardized regression-based (SRB) change score allows investigators to define clinically relevant cognitive change on an individual basis controlling for these confounding factors. We performed a preliminary study to test its applicability and usefulness in the neuropsychological diagnosis of dementia. We derived a regression equation for the tests of a widely used Italian battery for global cognitive assessment, the Mental Deterioration Battery, in a sample of 20 normal elderly and we tested the potential clinical application of the SRB methodology in two cases of questionable dementia.

Aged↗

[Cytofluorimetric evaluation of peripheral blood dendritic cells in patients with Mediterranean Kaposi's sarcoma].

AIM: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized by angiomatous nodules and plaques that mainly affect the skin. The disease is consistently associated with human herpesvirus-8 (HHV8) and with a state of preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in the activation and function of both innate and adaptative immune responses. At least 2 distinct subsets have been characterized in peripheral blood based on phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral and antitumor induced responses, we hypothesized that DCs could be involved in the onset and evolution of KS. METHODS: Thirty-five patients with mediterranean KS assigned to different clinical stages were compared with 51 healthy control subjects. Peripheral blood DCs were quantified and functionally characterised by flow cytometry directly on whole blood samples. The production of the regulatory cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after incubation with or without lipopolysaccharide (LPS). RESULTS: Myeloid DCs identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+ cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from KS patients were more mature, as assessed by expression of the maturation marker CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as compared with controls. CONCLUSION: The numerical and functional alterations of peripheral blood DCs observed in KS patients suggest an involvement of these cells in the onset and evolution of the disease.

Aged↗

Screening cognitive decline in dementia: preliminary data on the Italian version of the IQCODE.

The IQCODE is a retrospective questionnaire for caregivers about changes which occurred in a patient's cognitive and functional efficiency in the previous 10 years of life. Previous studies demonstrated the validity of the IQCODE for the screening of dementia similar to that of traditional cognitive screening tests, with the additional advantage of allowing the detection of cognitive change, rather than just cognitive impairment. The present paper deals with the preliminary results of the validation of the Italian version of the questionnaire in a sample of 45 mild to severely demented patients and 13 patients with mild cognitive impairment (MCI), compared to 20 cognitively intact elderly subjects. The IQCODE demonstrated satisfactory discriminative power for dementia as well as for MCI and a good correlation with the MMSE.

Aged↗

T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

Adult↗

Mucosal and systemic immune activation is present in human immunodeficiency virus-exposed seronegative women.

Immune parameters were analyzed in peripheral blood mononuclear cells (PBMC) and cervical mucosa biopsy specimens of human immunodeficiency virus (HIV)-seronegative women sexually exposed to HIV (exposed seronegative [ESN]), HIV-infected women, and healthy women without HIV exposure. HIV was not detected in PBMC or cervical mucosa biopsy specimens of ESN women. However, interleukin (IL)-6, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha and -beta mRNA were elevated in PBMC and cervical mucosa biopsy specimens of ESN and HIV-infected women; CCR5 and CXCR4 mRNA were augmented in cervical mucosa biopsy specimens, but not in PBMC, of ESN and HIV-infected women; HIV-specific IFN-gamma-secreting cells were detected in vaginal washes of ESN and HIV-infected women; and phenotypic alterations were present in PBMC of ESN women. These results suggest that active HIV infection is not required for T cell activation; immune alterations occur in women in whom HIV infection cannot be detected virologically or clinically.

Cytokines↗

Tuberculosis in the urban poor settlements in the Philippines.

SETTING: Urban poor settlements in the Philippines. OBJECTIVE: To determine the magnitude of the tuberculosis problem in urban poor settlements in comparison with urban areas studied in the Nationwide Tuberculosis Prevalence Survey. STUDY DESIGN AND METHOD: A multistage cluster survey of BCG scar, tuberculin test, chest radiography and sputum examination for bacillary disease, in urban poor areas. RESULTS: The prevalences of culture-positive and smear-positive tuberculosis were 17.5 +/- 2.3 (95% CI 13.3-22.4) and 7.9 +/- 2.3 per thousand (95% CI 2.611.5), respectively. Extrapolated to the total population, the rates in the urban poor settlements were 12.4 +/- 1.7 (95% CI 9.6-16.2) and 5.6 +/- 1.6 per thousand population (95% CI 1.3-8.3), respectively. The prevalence of active pulmonary tuberculosis in subjects aged 10 years or more was 66 +/- 5.6/1000 (95% CI 55-77). The BCG vaccination rate was 72%. The overall prevalence of tuberculosis infection was 66%, and 39% in those aged 5-9 years, corresponding to an annual risk of infection (ARI) of 6.5%. CONCLUSION: The problem of tuberculosis was substantial in the urban poor settlements, and was appreciably worse than that in the general urban population.

Adolescent↗

BCG coverage and the annual risk of tuberculosis infection over a 14-year period in the Philippines assessed from the Nationwide Prevalence Surveys.

SETTING: A prevalence survey of tuberculosis (TB) infection was undertaken in the Philippines, a developing country in the Western Pacific region. OBJECTIVE: To determine the bacille Calmette Guerin (BCG) vaccination rate, the prevalence of TB infection and the annual risk of TB infection (ARTI). METHODS: A nationwide stratified multi-stage cluster survey of 21,960 individuals. BCG scar verification and tuberculin test were performed on those aged > or =2 months. The ARTI was calculated using the prevalence rates of TB infection in children aged 5-9 years. RESULTS: BCG scars were noted in 66% of the study population. The prevalence of TB infection was 63.4% among unvaccinated individuals. The prevalence rate was higher in males in both urban and rural areas. With both sexes combined, urban and rural communities had similar prevalence rates. In children aged 5-9 years, the prevalence rate was 16.1% (males 17.4%, females 14.9%), corresponding to an ARTI of 2.3% (males 2.5%, females 2.1%). CONCLUSION: BCG coverage increased substantially between 1981-1983 and 1997. The ARTI, however, was virtually unchanged, indicating that morbidity due to TB continued to be high.

Adolescent↗

Bacillary disease and health seeking behavior among Filipinos with symptoms of tuberculosis: implications for control.

SETTING: Urban and rural communities and urban poor settlements in the Philippines. OBJECTIVE: To determine bacillary disease and action taking among individuals with symptoms of tuberculosis (TB), and to analyze their implications for TB control. STUDY DESIGN AND METHOD: Subjects aged 20 years and older were interviewed in the 1997 nationwide stratified multi-cluster survey. Sputum acid-fast smears and cultures were done in subjects with abnormal screening chest radiographs. RESULTS: Individuals with TB symptoms comprised 18.1% of the population studied. The prevalence of bacillary disease was 39/1000 in symptomatic subjects compared to 13/1000 in asymptomatic subjects. Symptom screening had a 14.3% positive predictive value and a 91.4% negative predictive value for bacillary disease. Significantly more symptomatic than asymptomatic subjects attended chest radiographic screening during the survey. However, in response to their symptoms, the majority (43.0%) took no action or self medicated (31.6%), while 11.8% consulted a private practitioner, 7.5% a public health center, 4.4% a hospital, and 1.7% a traditional healer. CONCLUSION: Sputum smear examination after symptom screening was acceptable for case finding. The health seeking behavior of subjects with TB symptoms was inappropriate. A health education program and public-private collaboration in directly observed therapy, short course (DOTS) are essential for TB control in the Philippines.

Adult↗

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis.

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.

Acute Disease↗

Altered signaling lymphocytic activation molecule (SLAM) expression in HIV infection and redirection of HIV-specific responses via SLAM triggering.

Signaling lymphocytic activation molecule (SLAM) is a transmembrane lymphocytic receptor which gets rapidly upregulated following cell activation. SLAM engagement augments T cell expansion and interferon-gamma (IFN-gamma) production independently of CD28. SLAM signaling is regulated by the SLAM-associated protein. We evaluated the expression and function of SLAM on CD4(+) and CD8(+) lymphocytes in HIV-infected individuals with either recently acquired infection (Group A) or asymptomatic HIV infection (Group B) and in healthy controls (HC). Soluble antigen (HIV env peptides and tetanus toxoid)- and mitogen-stimulated proliferation and IFN-gamma and IL-10 production upon SLAM costimulation were also measured. Results showed that: (1) SLAM-expressing CD4(+) and CD8(+) lymphocytes diminish in group A patients compared to both group B patients and HC; (2) SLAM expression on CD4(+) lymphocytes is preferentially associated with the lack of CD7 on cell surface (CD4(+)CD7(-) produce IL-10 but not IFN-gamma); (3) SLAM engagement increases HIV env peptide-stimulated, but neither tetanus toxoid- nor PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) in patients but not in HC; and (4) SLAM engagement augments IFN-gamma and reduces IL-10 production by env peptide-stimulated PBMC of HIV-infected individuals. These results demonstrate that early HIV infection results in an altered SLAM expression which correlates with a time-limited impairment of cell-mediated immunity. Furthermore, they show that triggering via SLAM potentiates HIV-specific proliferative responses with simultaneous downregulation of IL-10 and redirection of the response to TH0/TH1.

Adult↗

A role for mucosal immunity in resistance to HIV infection.

In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House. Avon Books, New York, 1997), two characters discuss love and its impossibilities. One brashly claims to be "immune to love", explaining the concept to his perplexed interlocutor, "...people become immune to love like they become immune to any disease. Either they had it bad early in life, like chicken pox and that's that; or they keep getting exposed to it in little doses and build up an immunity; or somehow they just don't catch it, something in'em is born resistant. I'm the last type. I'm immune to love and poison ivy". (p. 275) (E. McCracken, The Giant's House. Avon Books, New York, 1997). Substitute the words 'HIV infection' for 'love' and this intriguing metaphor summarizes the state of the art working hypotheses for the phenomenon of resistance to HIV infection in HIV-exposed individuals who, against all odds, do not seroconvert. These hypotheses will be discussed hereafter and particular emphasis will be placed upon a possible role for mucosal immunity in this phenomenon.

Chemokines↗

Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons.

The presence and activity of human immunodeficiency virus (HIV)-specific antibodies were analyzed in the sera of 15 sexually exposed seronegative persons who had systemic HIV-specific cell-mediated immunity and IgA-mediated mucosal immunity and in their HIV-infected partners. The HIV-positive subjects had HIV-specific serum IgG and IgA; the seronegative persons had HIV-specific serum IgA in the absence of IgG. Testing of the seronegative persons 1 year after the interruption of at-risk sex showed that no IgG seroconversion had occurred and that HIV-specific IgA serum concentrations had declined. Serum from the HIV-exposed seronegative persons was analyzed for the ability to neutralize primary HIV-1 isolates. Neutralizing activity was detected in 5 of 15 sera and in 2 cases was retained by serum-purified IgA. Thus, the immunologic picture for resistance to HIV infection should include HIV-specific cell-mediated immunity as well as HIV-specific IgA-mediated mucosal and systemic immunity.

Female↗

The 1997 Nationwide Tuberculosis Prevalence Survey in the Philippines.

SETTING: The Philippines is a developing country where tuberculosis (TB) remains a significant public health problem. OBJECTIVE: To determine the prevalence of TB as a basis for setting the targets of the National Tuberculosis Control Program. STUDY POPULATION AND METHODS: A multi-stage cluster survey of a random sample of 21960 subjects from 36 clusters nationwide was undertaken from 2 April to 31 July 1997. BCG scar verification and tuberculin testing was performed for subjects aged 2 months and over, and chest radiography screening was done on subjects 10 years and older. Sputum samples were collected from individuals who were initially assessed to have abnormal chest radiographs to determine the prevalence of bacillary tuberculosis. Acid-fast smear by modified Kinyoun's technique and culture on Löwenstein Jensen were done to demonstrate Mycobacterium tuberculosis. RESULTS: The prevalence of active pulmonary TB was 42/1000 population. The prevalence of culture-positive and smear-positive cases was 8.1 and 3.1/1000, respectively. The prevalence was similar in urban and rural areas. CONCLUSION: Morbidity from TB remains high. Allowing for methodological differences from the survey in 1981-1983, the prevalence of active pulmonary TB was unchanged. There was only a minimal decrease, of 37% for smear-positive cases and 25% for culture-positive cases, in the 14-year interval.

Adolescent↗