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Biomedical subjects

L Villa

Publications and source records attributed to L Villa.

At least 19 recordsLinked to original sources

Discriminative and predictive power of an informant report in mild cognitive impairment.

BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) requires caregivers to rate decline in patients' cognitive and functional performance and has never been used for mild cognitive impairment (MCI). METHODS: We contrasted the discriminative and predictive power of the IQCODE with that of the Mini Mental State Examination (MMSE) and a verbal episodic memory measure, the Rey's Auditory Verbal Learning Test (RAVLT), in 45 patients with MCI (mean (SD) age at baseline: 71.6 (4.7) years) and 30 outpatients with dementia (70.5 (6.3) years) attending the Neuropsychology Service, St Gerardo Hospital, and compared them with 55 cognitively intact elderly people (70.7 (7.1) years). Patients with MCI were followed up for at least 2 years or until conversion to dementia. RESULTS: In total, 24 patients with MCI (53.3%) had converted to dementia at follow up (mean (SD) duration of follow up 17.0 (7.3) months for converters and 35.0 (7.1) months for non-converters). At baseline, the ability to differentiate patients with MCI from healthy controls was similar for the IQCODE (area under the curve (AUC) 0.86) and the MMSE (AUC 0.84; z = 0.53, not significant). As predictors of conversion to dementia, a trend favouring the IQCODE (AUC 0.86) with respect to immediate (AUC 0.74) and delayed (AUC 0.75) recall on the RAVLT was apparent (z = 1.36, p = 0.087 versus immediate recall, z = 1.51, p = 0.064 versus delayed recall). The independent predictive ability of IQCODE and memory scores was evaluated through logistic regression, and the questionnaire alone yielded the best correct classification of 81%. CONCLUSIONS: The IQCODE is an informant based measure of cognitive decline that may provide a relevant contribution to the diagnostic and prognostic investigation of patients with MCI.

Adult↗

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

Child↗

Comparison of multidrug resistance gene regions between two geographically unrelated Salmonella serotypes.

OBJECTIVES: The aim of this study was to identify chromosomally integrated genes conferring multidrug resistance to a Salmonella enterica (S.) serotype Typhimurium isolate, phage type DT193, isolated in Ireland and to compare them with resistance genes conferring plasmid-mediated multidrug resistance to a S. Enteritidis isolate from Italy. METHODS: A complete DNA sequence of the regions containing the resistance genes was obtained from the chromosome of the S. Typhimurium DT193 isolate and from the IncI plasmid of the S. Enteritidis isolate. The plasmid was also characterized by conjugation and incompatibility grouping. RESULTS: Two 10 kb multidrug resistance non-Salmonella Genomic Island 1 type clusters were independently identified in the S. Enteritidis plasmid and in the chromosome of the S. Typhimurium isolate. Detailed characterization identified an IP-type 2 integron containing a dfrA1-aadA1 gene cassette and other common resistance determinants derived from the RSF1010 plasmid. CONCLUSIONS: These multidrug resistance regions originate following chromosomal integration of key resistance markers encountered on plasmids circulating in other Salmonella serotypes. This mechanism of marker acquisition may have future implications for the evolution of similar structures in previously susceptible serotypes, leading to an increased public health risk.

Chromosome Mapping↗

CMY-13, a novel inducible cephalosporinase encoded by an Escherichia coli plasmid.

An IncN plasmid (p541) from Escherichia coli carried a Citrobacter freundii-derived sequence of 4,252 bp which included an ampC-ampR region and was bound by two directly repeated IS26 elements. ampC encoded a novel cephalosporinase (CMY-13) with activity similar to that of CMY-2. AmpR was likely functional as indicated in induction experiments.

Cephalosporinase↗

Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis.

CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance.

Arthritis, Rheumatoid↗

Cytokine gene therapy of gliomas: effective induction of therapeutic immunity to intracranial tumors by peripheral immunization with interleukin-4 transduced glioma cells.

To provide a means for comparing strategies for cytokine gene therapy against intracranial (i.c.) tumors, we generated rat gliosarcoma 9L cells transfected with interleukin-4 (9L-IL4), interleukin-12 (9L-IL12), granulocyte-macrophage colony-stimulating factor (9L-GMCSF) or interferon-alpha (9L-IFNalpha). To simulate direct and highly efficient cytokine gene delivery, cytokine transfected 9L tumors were implanted i.c. into syngeneic rats. i.c. injection led to tumor-outgrowth in the brain and killed most animals, whereas these cell lines were rejected following intradermal (i.d.) injection. Cytokine-expressing i.c. 9L tumors, however, had a greater degree of infiltration by immune cells compared with control, mock-transfected 9L-neo, but to a lesser degree than i.d. cytokine-expressing tumors. Tumor angiogenesis was suppressed in cytokine-transfected tumors. In a prophylaxis model, i.d. vaccination with 9L-IL4 resulted in long-term survival of 90% of rats challenged i.c. with parental 9L; whereas 40% of 9L-GM-CSF, 40% of 9L-IFNalpha and 0% of 9L-IL12-immunized rats were protected. In a therapy model (day 3 i.c. 9L tumors), only i.d. immunization with 9L-IL4 had long-term therapeutic benefits as 43% of rats survived >100 days. These data indicate that peripheral immunization with 9L-IL4 had the most potent therapeutic benefit among various cytokines and approaches tested against established, i.c. 9L tumors.

Animals↗

Synthesis, free solution capillary electrophoresis separation and toxicity of seven potential impurities of dobutamine.

The seven O-methylated analogs of dobutamine [(+/-)-4-[2-[[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl]pyrocatechol, CAS 34368-04-2), a trihydroxy secondary amine, can be considered potential impurities of the latter, the ultimate step of the synthesis of dobutamine being the deprotection of the three phenolic groups. In order to enable the detection and the identification of such a contamination, the di- and the monomethylated derivatives of dobutamine were prepared and their mixture with dobutamine and its trimethoxy precursor completely resolved by Free Solution Capillary Electrophoresis (FSCE). Indeed, the above impurities proved to occur in dobutamine in consequence of improper demethylation conditions and to be significantly more toxic than the latter.

Adrenergic beta-Agonists↗

Tirane, Albania: survey on drinking water quality and facilities.

To develop a realistic model of the situation, a study was carried out in four different socioeconomic and hygienic areas of Tirane, namely in the modern and historical centre as well as in the intermediate and peripheral areas. In each area interviewers from the city's Public Health Directorate, contacted randomly, door-to-door, the residents, submitting a questionnaire and collecting water samples at the same time. Our data show relevant differences regarding distribution and quality of drinking water between the centre and peripheral areas. One third of water samples revealed the presence of microorganisms, whereas one fifth had no residual chlorine. Altogether more than 200,000 people in the peripheral areas of Tirane live under low level hygienic conditions. The recent outbreaks of cholera, poliomyelitis and the hyperendemic hepatitis A disease are the dramatic results of the low quality drinking water.

Albania↗

2-Hydroxymethyl-1,4-dioxane: synthesis, resolution and determination of the absolute configurations of the enantiomers.

2-Hydroxymethyl-1,4-dioxane 3 was resolved via salt formation between its hydrogen phthalate and (R)- or (S)-1-phenylethylamine, selective crystallization of the resultant diastereomeric mixtures and subsequent recovery of its enantiomers by saponification. The progress of the resolution was followed by chiral HPLC and the absolute stereochemistry of the two enantiomers determined by comparison of their specific rotations with that of (R)-3 synthesized from enantiomerically pure (R)-1-O-benzylglycerol. The results of the synthesis of 3 and of its resolution are discussed and compared with those previously obtained for 1,2-isopropylidene glycerol evaluating the consequences of replacement of ispropylidene with an ethylene bridge.

Journal Article↗

Comparison between hybrid capture II and polymerase chain reaction results among women at low risk for cervical cancer.

PURPOSE: Hybrid Capture (HC) is a new and powerful tool to detect DNA/RNA of several infectious agents. Regarding HPV DNA detection HC II has shown no false positive results due to contamination and its inter-laboratory reproducibility reaches 98%. It is also simpler and costs less than other methods such as Polymerase Chain Reaction (PCR) and it has shown a high correlation to clinical findings. Our objective is to compare HC II and PCR results among women at low risk for cervical cancer.METHODS: This is a cross-sectional study which enrolled 977 asymptomatic women aged 15 and 70 years. Squamous columnar junction samples were obtained and analyzed for HPV DNA either by HC II and PCR. Epidemiological factors and cyto-pathologic results were related to HPV DNA status. The Pearson Chi-square test and multiple logistic regression were performed to relate epidemiological and cytopathological variables and HPV DNA status.RESULTS: About 15.4% and 15.9% of women were HPV DNA positive by HC II and PCR respectively. Both were highly associated with cytology (P < 0.0001). The correlation to histopathology was also good with a higher significance for HC II. Factors related to HPV DNA detection by PCR were: oral contraceptive use (OR = 1.26; 95% CI = 1.2-1.62); history of genital HPV infection (2.11; 1.13-4.59); 3 or more sexual partners (1.35; 1.10-1.83); education (<primary (1.43; 1.01-1.99); secondary (1.42; 1.03-1.99). For the HC II the related variables were: being single (1.26; 1.01-1.62); aged sixteen years or less at first sexual intercourse (1.37; 1.03-1.89).CONCLUSIONS: The results suggest that HC II is highly comparable to PCR regarding HPV DNA detection. HC II is also significantly associated with cytology and histopathology results indicating that it may be used as adjunctive or stand-alone test for screening programs.

Journal Article↗

Seroepidemiology of Hantavirus in the Philippines.

OBJECTIVE: This study was undertaken to determine the seroepidemiology of Hantavirus infection in the Philippines. METHODS: This is a cross-sectional study done in asymptomatic volunteers from various communities in the Philippines selected by a stratified multistage sampling design. Antibody to Hantavirus was detected by particle agglutination (PA) test using Hantadia high-density particle agglutination (HDPA) reagent kit. RESULTS: The prevalence of positive Hantavirus antibody among 461 subjects was the same in both males (6.1%) and females (6.1%) in rural (7.6%), urban (5.6%), and urban poor (5.1%) populations. CONCLUSIONS: The prevalence of Hantavirus infection in the Filipino population is comparable to that seen in other developing countries. The HDPA can be conveniently used as a rapid tool to detect the Hantavirus antibody for seroepidemiologic and diagnostic purposes.

Adult↗

Fetal hydrops due to a tachyarrhythmia progressing to organic pulmonary stenosis.

We discovered supraventricular tachycardia with advanced hydrops in the setting of normal cardiac anatomy at 26 weeks of gestation which resolved successfully following administration of digoxin and flecainide to the mother. A female baby was born after a premature rupture of the membranes at 30.6 weeks. The neonate was in sinus rhythm, showed a progressive regression of right ventricular insufficiency, but developed signs of acquired pulmonary valvar and subvalvar stenosis at 2 months of age.

Adult↗

Multiple-antibiotic resistance mediated by structurally related IncL/M plasmids carrying an extended-spectrum beta-lactamase gene and a class 1 integron.

A conjugative IncL/M plasmid (pSEM) conferring resistance to gentamicin, amikacin, kanamycin, sulfonamides, and expanded-spectrum cephalosporins was found in pathogenic strains of Salmonella enterica serotype Typhimurium. Resistance to aminoglycosides was encoded by a sul1-type class 1 integron (In-t3). An extended-spectrum beta-lactamase gene, bla(SHV-5), was identified 3. 5 kb downstream of the integrase (intI1) gene of In-t3. Nucleotide sequence analysis of the 5.3-kb bla(SHV-5)-In-t3 region of pSEM highlighted striking similarities with IncL/M plasmids isolated from nosocomial gram-negative pathogens, conferring resistance to expanded-spectrum cephalosporins and aminoglycosides.

Aminoglycosides↗

Hormonal modulation of GM-CSF receptor alpha-chain in in vitro models of endometrial cancer.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates the proliferation and differentiation of bone marrow progenitors. Moreover, the presence and activity of GM-CSF and its receptor (GM-CSF-r) has been documented on tissues and cell lines of a non-hemopoietic origin. In this paper we studied the expression and putative role of GM-CSF and GM-CSF-r in endometrial cancer. The modulation of GM-CSF-r alpha-chain upon progesterone treatment suggests a role for GM-CSF and its receptor in the pathogenesis and development of endometrial cancer.

Dose-Response Relationship, Drug↗

Retinoids in breast cancer prevention and treatment. A review of the literature.

During the last three decades, research focused on cancer treatment has led to the development of many cytotoxic agents. Despite the fact that these efforts have significantly improved the prognosis of certain malignancies such as some lymphomas, leukemias and testicular carcinomas, other tumors such as ovarian, lung and metastatic breast cancer are still associated with a poor prognosis. An innovative approach has recently emerged, thanks to a better understanding of tumor cell biology and many efforts are aimed at finding compounds capable of restoring a more differentiated phenotype to tumor cells, thereby reducing the tumor's aggressiveness and ultimately reverting it to its normal counterpart [1, 2]. Retinoids are the prototype of this new therapeutical approach called "differentiation therapy".

Animals↗

Evolution and long term outcome in cases with fetal diagnosis of congenital heart disease: Italian multicentre study. Fetal Cardiology Study Group of the Italian Society of Pediatric Cardiology.

OBJECTIVES: To analyse the evolution and outcome in utero and after birth of infants with a fetal diagnosis of congenital heart disease. DESIGN: Inclusion criteria were the fetal diagnosis of congenital heart disease, confirmed postnatally or postmortem, and a complete follow up in utero and after birth. SETTING: 20 centres operating prenatal echocardiographic screening. PATIENTS: 847 cases were included in the study. Gestational age at diagnosis ranged from 15-39 weeks; in 370 cases (43.7%) the diagnosis was made before 24 weeks' gestation. RESULTS: 245/847 cases (28.9%) were terminated during pregnancy, 227 following early diagnosis; 128/245 cases (52. 2%) had associated anomalies and 117/245 (47.8%) had serious congenital heart disease. Of the remaining 602 cases that continued the pregnancy, 72 (11.9%) died in utero, 259 (43%) died postnatally (83 after surgery or invasive procedures), and 271 infants (45%) survived and presently range in age from 18 months to 13 years old. The mortality rate was higher in cases with associated extracardiac or chromosomal anomalies (68% and 74% of cases continuing pregnancy, respectively), and in cases with heart failure and complex cardiac defects. CONCLUSIONS: The data confirm a relevant fetal and postnatal loss in cases with complex congenital heart disease, and major clinical use of prenatal diagnosis in the management of ductus dependent anomalies. Negative prognostic factors for the outcome were associated anomalies and heart failure.

Abortion, Therapeutic↗

Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig-McGill Study Group.

This article reports on a large longitudinal study, begun in 1993, of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a population of low-income women in São Paulo, Brazil, a city with one of the highest risks worldwide for cervical cancer. Known as the Ludwig-McGill cohort study, the epidemiological investigation focuses on persistent infection with oncogenic HPV types as the precursor event leading to cervical neoplasia. The objectives of this study are to: 1) study the epidemiology of persistent cervical HPV infection in asymptomatic women, 2) investigate whether persistent HPV infection increases risk of low-grade and high-grade cervical lesions, 3) search for determinants of persistent HPV infection, 4) search for molecular variants of HPV that may be associated with an increased risk of lesions, 5) investigate whether viral burden is correlated with persistent infections and with lesion risk, 6) study the antibody response to HPV as a predictor of persistence and lesion progression, and 7) examine the role of HLA typing and codon 72 p53 gene polymorphism in mediating HPV persistence and lesion severity. The study accrued 2,528 female subjects through March 1997. Subjects were followed up every 4 months in the first year, with twice-yearly return visits to take place in subsequent years. Participants undergo a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and have a blood sample drawn for HPV antibody testing. A cervicography is performed once in the first year and every two years thereafter. In this article we describe the design and methods of the study, provide baseline cohort characteristics, and present a preliminary assessment of the prognostic value of baseline HPV status.

Adult↗