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1.
HIV Med ; 21(10): 642-649, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32876382

RESUMO

OBJECTIVES: Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as compared to the general population (non-PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach. METHODS: A population-based, nationwide, retrospective cohort study was conducted among Italian people, aged 15-74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex- and age-standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non-PWA mortality rates. RESULTS: Among 7912 PWA (34 184 person-years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2-43.8) for all liver diseases, 131.1 (95% CI 118.3-145.0) for viral hepatitis, 29.9 (95% CI 27.0-33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1-15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15-49 years and those infected by injecting drug use. CONCLUSIONS: The high excess liver-related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users.


Assuntos
Síndrome da Imunodeficiência Adquirida/mortalidade , Hepatopatias/mortalidade , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
2.
Sci Rep ; 10(1): 250, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937857

RESUMO

The influence of microgeometries on the Secondary Electron Yield (SEY) of surfaces is investigated. Laser written structures of different aspect ratio (height to width) on a copper surface tuned the SEY of the surface and reduced its value to less than unity. The aspect ratio of microstructures was methodically controlled by varying the laser parameters. The results obtained corroborate a recent theoretical model of SEY reduction as a function of the aspect ratio of microstructures. Nanostructures - which are formed inside the microstructures during the interaction with the laser beam - provided further reduction in SEY comparable to that obtained in the simulation of structures which were coated with an absorptive layer suppressing secondary electron emission.

3.
Int J Clin Pharm ; 40(4): 795-802, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29785683

RESUMO

Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Terapia de Alvo Molecular/efeitos adversos , Farmacêuticos , Farmacovigilância , Papel Profissional , Inibidores de Proteínas Quinases/efeitos adversos , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Itália/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Segurança do Paciente , Satisfação do Paciente , Projetos Piloto , Estudos Prospectivos , Medição de Risco , Fatores de Risco
4.
Public Health ; 142: 39-45, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28057195

RESUMO

OBJECTIVES: Despite the wide accessibility to free human immunodeficiency virus (HIV) testing and combined antiretroviral therapy (cART), late HIV diagnosis remains common with severe consequences at individual and population level. This study aimed to describe trends of late HIV testing and to identify their determinants in the late cART era in Italy. STUDY DESIGN: We conducted a population-based, nationwide analysis of the Italian National AIDS Registry data (AIDS - acquired immune deficiency syndrome) for the years 1999-2013. METHODS: Late testers (LTs) were defined as people with AIDS (PWA) whose first HIV-positive test preceded AIDS diagnosis by 3 months or less. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were estimated to examine factors associated with being LTs. Joinpoint analysis was used to estimate annual percent changes (APCs) of LTs' proportion over time. RESULTS: Among 20,753 adult PWA, 50.8% were LTs. Italian PWA showed a lower proportion of LTs than non-Italian PWA (46.5% vs 68.2%). Among Italian PWA, the odds of being LTs was higher in men than in women (OR = 2.62, 95% CI: 2.38-2.90); in the age groups below 35 years and over 49 years at diagnosis (OR = 1.24, 95% CI: 1.12-1.37 and OR = 1.51, 95% CI: 1.38-1.67, respectively) vs PWA aged 35-49 years; and in those infected through sexual contact as compared with injecting drug use (OR = 13.34, 95% CI: 12.06-14.76 for heterosexual contact and OR = 8.13, 95% CI: 7.30-9.06 for male-to-male sexual contact). The proportion of LTs increased over time among Italians, especially in the latest period (APC2006-2013 = 5.3, 95% CI: 3.8-6.9). The LTs' proportion resulted higher, though stable, among PWA aged ≥50 years. Conversely, an increasing trend was observed among PWA aged 18-34 years (APC = 5.3, 95% CI: 4.5-6.1). The LTs' proportion was persistently higher among PWA who acquired HIV infection through sexual contact, even if a marked increase among injecting drug users was observed after 2005 (APC = 11.4, 95% CI: 5.7-17.5). CONCLUSIONS: The increasing trend of LTs' proportion in the late cART era highlights the need of new strategies tailored to groups who may not consider themselves to be at a high risk of infection. Active promotion of early testing and continuous education of infection, especially among young people, need to be implemented.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Diagnóstico Tardio/estatística & dados numéricos , Infecções por HIV/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Adulto Jovem
5.
Q J Nucl Med Mol Imaging ; 52(1): 84-88, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17538521

RESUMO

AIM: Adrenal incidentalomas (AI) are defined as asymptomatic adrenal masses occasionally discovered during high-resolution imaging procedures, as computed tomography or magnetic resonance. Pheochromocytoma, a chromaffin tumour, must be excluded before any invasive diagnostic or therapeutic procedure, in order to avoid dangerous acute catecholamines-release into blood stream. Chromogranin-A (CgA) is a member of the granin family contained in secretory vesicles of chromaffin system. This study investigated the performance of serum CgA in detecting or excluding pheochromocytoma among patients with AI. METHODS: We enrolled 348 patients by AI > 20 mm without clinical or biochemical signs for corticosteroids overproduction. Serum CgA was assayed by a specific immunoradiometric method and a [123I] metaiodobenzylguanidine (MIBG) scan was performed in the 39 CgA-positive patients. RESULTS: Eighteen out of these patients showed a positive scan and were submitted to laparoscopic adrenalectomy. Pheochromocytoma was histologically confirmed in all cases . The patients with positive serum CgA, were reassessed 1 year later by clinical examination and serum CgA assay. None of patients developed clinical symptoms of chromaffin-tissue hyperactivity , nor showed a serum CgA increase. Serum levels of CgA were significantly higher inpatients with pheochromocytoma than inpatients without (P<0.0001). CONCLUSION: We concluded that serum CgA assay is effective as a single marker to detect or exclude sporadic pheochromocytoma among patients with AI > 20mm. Particularly, a negative serum CgA assay may be used to rule out [123I] MIBG imaging and /or other diagnostic procedures.


Assuntos
3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/sangue , Cromogranina A/sangue , Feocromocitoma/diagnóstico , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico por imagem
6.
Cancer Genet Cytogenet ; 165(2): 106-13, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16527604

RESUMO

Deletion of chromosome arm 6q is a frequent karyotypic alteration found in a variety of cancers and lymphoproliferative disorders, including leukemia and lymphomas. We characterized 6q deletions in 35 malignant lymphomas, using conventional and molecular cytogenetic approaches, to define the deletion pattern of 6q in different histological types. Conventional cytogenetics revealed a 6q deletion in 46% of lymphomas, including two cases that showed 6q deletion as the sole chromosome anomaly. Interphase FISH analysis demonstrated allelic loss of 6q regions in 33 out of 35 cases (94.2%); the deletions were discontinuous, involving nonadjacent molecular regions. Although 6q deletion is a common event in all types of lymphomas, specific deletion patterns seem to characterize different histological types, suggesting that different tumor suppressor genes play different roles in different types of lymphomas. Two specific 6q regions deleted in diffuse large B cell lymphomas but not in follicular lymphomas may be implicated in the clinical transformation.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 6 , Doença de Hodgkin/genética , Linfoma não Hodgkin/genética , Cromossomos Artificiais de Levedura , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem
7.
Ann Oncol ; 16(7): 1169-76, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15851403

RESUMO

BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of all B-cell lymphomas and has poor response to conventional therapy. It is characterized by the presence of a chromosomal translocation t(11:14) (q13;q32) which results in deregulated cyclin D1 expression. Since defects in cell cycle regulation and apoptosis are primary events in MCL, small-molecule inhibitors of cdks-cyclins may play an important role in the therapy of this disorder. CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T. MATERIALS AND METHODS: The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. The effect of CYC202 on the cell cycle and on apoptosis-, cell-cycle- and transcription-regulation-related proteins was assessed. RESULTS: The IC50 was 25 microM for REC, Granta-519 and JeKo-1 cells and 50 microM for NCEB-1 cells. CYC202 caused an accumulation of cells in the G2-M phase of the cell cycle and apoptosis. CYC202 caused down-regulation of cyclin D1 and Mcl-1 protein levels, possibly because of the inhibition of transcription elongation. CONCLUSIONS: Our data suggest that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype.


Assuntos
Antineoplásicos/uso terapêutico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Linfoma de Célula do Manto/tratamento farmacológico , Purinas/uso terapêutico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Marcação In Situ das Extremidades Cortadas , Purinas/farmacologia , Roscovitina , Fatores de Transcrição/metabolismo
8.
J Biomed Mater Res ; 54(1): 20-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11077399

RESUMO

Hydrogen desorption from argon plasma-treated titanium implants with a high surface roughness was studied. Implants with a high surface roughness have shown an increase in mechanical stability in bone tissue and a different behavior of osteoblasts in vitro. High surface roughness was produced by grit blasting and acid etching, resulting in an increase of the sub-surface hydrogen concentration and the formation of a titanium hydride. After an argon plasma treatment the surface oxide, which always covers titanum surfaces exposed to an oxygen-containing environment, and some of the hydrogen were sputtered away, decreasing the hydrogen concentration in the sub-surface region. Nuclear reaction analysis was used to determine the hydrogen concentration as a function of depth. The total amount of sub-surface (down to a depth of < or = 2 microm) hydrogen remaining after plasma treatment decreased with increasing plasma intensity to below the levels observed in non-acid-etched samples (approximately 1-2%). Thermal desorption spectroscopy was used for desorption studies and investigation of H(2) desorption activation energies. With a surface oxide present, the onset of hydrogen desorption is at ca 400 degrees C, which is the oxide decomposition temperature in vacuum, with an activation energy of ca 2 eV/molecule of H(2). After plasma treatment, that is, without surface oxide present, the onset of desorption was observed at ca 300 degrees C and with an activation energy of ca 0.8 eV/molecule of H(2), indicating a bulk diffusion-limited desorption.


Assuntos
Materiais Biocompatíveis , Hidrogênio/química , Próteses e Implantes , Titânio , Ácidos , Fenômenos Químicos , Físico-Química , Microscopia Eletrônica de Varredura , Espalhamento de Radiação , Propriedades de Superfície , Termodinâmica , Titânio/química , Difração de Raios X
10.
J Neurooncol ; 48(2): 131-4, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11083076

RESUMO

The authors report a case of pineocytoma in a 44-year-old woman suffering from headache, vomiting and Parinaud syndrome. At histopathological examination the neoplasm showed a ill-defined lobulate pattern with some small pineocytomatous rosettes. The electron-microscopy revealed cells of moderate size and oval nuclei with smooth nuclear envelopes; well-developed organelles were found in the, abundant cytoplasm. The chromosome analysis revealed this kariotype: 58-59, XXX, -4, -5, -13, - 14, -15, + 19. This is the first report of a pineocytoma with ultrastructural and cytogenetic study; it confirms the literature findings of the electron-microscopy, whereas there is partial accordance with the previous cytogenetic studies.


Assuntos
Aneuploidia , Neoplasias Encefálicas/ultraestrutura , Aberrações Cromossômicas , Glândula Pineal/ultraestrutura , Pinealoma/ultraestrutura , Adulto , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Derivações do Líquido Cefalorraquidiano , Deleção Cromossômica , Feminino , Humanos , Cariotipagem , Proteínas de Neoplasias/análise , Fosfopiruvato Hidratase/análise , Glândula Pineal/cirurgia , Pinealoma/química , Pinealoma/patologia , Pinealoma/cirurgia , Sinaptofisina/análise , Trissomia
11.
Mol Cell Endocrinol ; 161(1-2): 53-7, 2000 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-10773392

RESUMO

Secondary amenorrhoea with elevated gonadotrophins occurring under the age of 40 (premature ovarian failure (POF)), and at the age between 41 and 44 years (early menopause (EM)), respectively, affects 1-2% and 5% of women in the general population. Objective of this study was to evaluate the prevalence of familial cases of POF and EM and to assess the clinical and genetic characteristics of these patients. One hundred and sixty women with idiopathic secondary amenorrhoea before the age of 45 and serum follicle-stimulating hormone (FSH) levels greater than or equal to 40 IU/l were included in the study. Tests performed on patients included complete medical history, pedigree's analysis, clinical pelvic examination, gonadotrophins and thyroid assessment, chromosomal analysis. The 160 patients included in the study showed idiopathic POF (n=130) or EM (n=30). Following pedigree assessment, we were able to identify an incidence of familial cases of 28.5% in the POF group (n=37) and of 50% in the EM group (n=15). POF and EM condition were often present in the same family. There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits. There was a statistically significant difference between sporadic and familial cases in age at POF onset: 32.0+/-7.3 years (12-40) compared to 35. 0+/-5.8 (18-40), respectively (P<0.05). The POF and EM families identified showed two or more affected females and transmission through either maternal or paternal relatives; in four families both maternal and paternal transmission was observed. This study suggests that idiopathic POF and EM conditions, differing only in age of menopause onset, may represent a variable expression of the same genetic disease. The different age of menopause onset in these patients may be explained by genetic heterogeneity and/or by different environmental factors. Our results indicate a high rate of familial transmission of the condition. Pedigree's analysis suggests an autosomal or an X-linked dominant sex-limited pattern of inheritance for POF and EM.


Assuntos
Menopausa Precoce/genética , Insuficiência Ovariana Primária/genética , Adolescente , Adulto , Amenorreia , Aberrações Cromossômicas , Transtornos Cromossômicos , Análise Citogenética , Saúde da Família , Feminino , Genótipo , Humanos , Itália/epidemiologia , Linhagem , Gravidez , Prevalência , Insuficiência Ovariana Primária/epidemiologia , Insuficiência Ovariana Primária/etiologia
12.
Tumori ; 86(6): 439-44, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11218182

RESUMO

AIMS AND BACKGROUND: Epidemiological investigations on the frequency of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are few and have shown a variable worldwide incidence ranging from 1% to 7% of all colorectal cancers (CRCs). In Italy, relevant differences have been observed: 2.8-3% of all CRCs in northern regions and less than 1% in southern regions. The aim of the present study was to investigate the HNPCC incidence in a selected area of northern Italy belonging to the Lombardy Cancer Registry. METHODS AND STUDY DESIGN: We analyzed 197 consecutive patients with newly diagnosed CRCs, histologically verified, and resident in two areas of the Lombardy Cancer Registry. For each case, genetic counseling with at least three generations pedigree reconstruction, HNPCC classification according to Amsterdam criteria, molecular analysis for microsatellite instability and immunohistochemistry for hMLH1 and hMSH2 were performed. RESULTS: A very low frequency (0.5%) of HNPCC fulfilling the Amsterdam criteria was found in comparison to the other Italian areas. Such an incidence seems to be due to actual population differences and reflects a genetic heterogeneity. CONCLUSIONS: The data underline the importance of a precise knowledge of actual HNPCC incidence in different populations in order to optimize effectiveness and efficiency of screening programs for the disease.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais Hereditárias sem Polipose/genética , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Sistema de Registros
13.
Hum Reprod ; 14(11): 2731-4, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10548611

RESUMO

Genetic factors may influence the timing of menopause. Premature ovarian failure (POF) has recently been identified as a genetic entity, but no genetic data are available on early menopause (EM). We investigated 36 patients with EM (age of menopause between 40 and 45 years of age) using cytogenetic and pedigree analysis. In 30 patients of this study the EM was idiopathic and 15 subjects (50%) had a familial condition of EM or POF. Pedigree analysis revealed a dominant pattern of inheritance of EM through maternal or paternal relatives. Our data reveal that POF and EM patients show the same genetic features and we postulate that these conditions may be a variable expression of the same genetic disease.


Assuntos
Menopausa Precoce/genética , Adulto , Feminino , Hormônio Foliculoestimulante/sangue , Deleção de Genes , Humanos , Pessoa de Meia-Idade , Linhagem , Cromossomo X
14.
Ann Oncol ; 10(7): 783-8, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10470424

RESUMO

BACKGROUND: Microsatellite instability (MSI), caused by a reduced efficacy of the DNA mismatch repair (MMR) machinery, represents a type of genomic instability frequently detected in HNPCC spectrum cancers and in a subset of sporadic carcinomas. The involvement of MSI in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has never been conclusively investigated. In this study, we tested the presence of MSI in tumor samples of patients harboring both MALT lymphomas and other types of malignancies. MATERIALS AND METHODS: We examined 10 microsatellite loci (D3S11, D3S1261, D3S1265, D6S262, D6S193, BAT-26, BAT-25, D17S250, APC, D2S123) out of a total of 34 primary tumors from 14 patients with MALT lymphomas and one or more additional neoplasms. The patients' MSI results were also tested for an association with a positive family history of cancer. RESULTS: MSI, defined by the presence of microsatellite alterations in more than 40% of the examined loci, was scored negative in all tumors studied, and pedigree analysis failed to identify any condition of familial cancer among the patients examined. CONCLUSIONS: The present study suggests that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of MALT lymphomas and associated neoplasms.


Assuntos
Linfoma de Zona Marginal Tipo Células B/genética , Repetições de Microssatélites , Neoplasias Primárias Múltiplas/genética , Neoplasias Gástricas/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo do DNA/genética , DNA de Neoplasias/genética , Humanos , Linhagem
15.
Gynecol Oncol ; 73(2): 247-52, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10329042

RESUMO

Fifty-one endometrial cancers were analyzed with regard to whether or how microsatellite instability (MI) was associated with the development of different types of endometrial malignant neoplasms. We investigated 6 loci previously reported as informative for colorectal cancer and a group of 8 loci located on 6q. Replication error (RER+) phenotype was detected in 10 of 51 (19.6%) endometrial cancers (ECs), all but one of which showed endometrioid differentiation. On the contrary, the RER+ phenotype was not detected in serous carcinomas and malignant mixed Müllerian tumors. MI was present in both early and advanced stage ECs. No correlation was found between age, grade, stage, familial pattern, mitotic index, and the RER+ phenotype of ECs. Only 1 of 8 endometrial carcinomas showing MI was associated with mutant p53 expression, while the majority of RER+ tumors were positive for estrogen and progesterone receptors. Our findings suggest that MI plays an early role in endometrial tumorigenesis and is significantly correlated with adenocarcinomas showing endometrioid features (EAs). The frequent involvement of the telomeric region of chromosome 6 in the MI of EA is an indication that this region may be crucial in the process of EA tumorigenesis.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Repetições de Microssatélites/genética , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/análise , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade
16.
Ann Oncol ; 9(8): 901-6, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9789614

RESUMO

BACKGROUND: Microsatellite instability (MI) is a biological characteristic of most tumors involved in hereditary non-polyposis colorectal cancer (HNPCC). This disease appears to be caused by germline mutations in mismatch repair (MMR) genes, which are responsible for repairing single base-pair mismatches. At least five human genes participate in MMR. MI also occurs in 10%-15% of sporadic colorectal cancers. Because MI detection has been suggested as an alternative diagnostic tool for identification of HNPCC families, in this study we analyzed the MI pattern in 100 consecutive colorectal carcinomas in order to correlate them with the clinicopathologic features and family histories of the patients. PATIENTS AND METHODS: A series of 100 colorectal cancers was evaluated for MI with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics. RESULTS: MI was detected in 36 of 100 cancers, 27 of which showed low instability and nine a high instability. The low- and high-instability cases showed similar clinicopathological characteristics, and significantly positive associations were observed between MI and mucinous histological type (P = 0.0001) and MI and peritumoral lymphocytic infiltration (P = 0.01). A single HNPCC family was identified in the high-grade MI group, while two families belonged to the MI-negative group. CONCLUSIONS: Our data suggest that MI screening is probably not an efficient strategy for identifying HNPCC cases. MI does, however, appear capable of defining a category of colorectal cancers with favourable prognostic features and should be investigated at least in all cases of mucinous adenocarcinomas.


Assuntos
Pareamento Incorreto de Bases , Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Repetições de Microssatélites/genética , Adulto , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fenótipo
17.
Hum Reprod ; 13(7): 1796-800, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9740426

RESUMO

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.


Assuntos
Insuficiência Ovariana Primária/genética , Adolescente , Adulto , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Menopausa/genética , Linhagem
18.
Clin Oral Implants Res ; 8(3): 208-16, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9586465

RESUMO

We present an investigation of the physico-chemical surface properties of commercially pure titanium coverslips which were submitted to various treatments designed to optimize their topography in view of application in oral implantology. The surface microroughness, chemical composition and water wettability were analyzed on titanium coverslips prepared by mechanical polishing, acid attack in HCl/H2SO4, after mechanical polishing or sandblasting, and titanium plasma-spray. The chemical composition has been measured by Auger electron spectroscopy. The treatments have no major influence on the surface chemical composition and all the samples display a composition approaching that of TiO2 with minor amounts of carbon, sulfur, silicon and calcium as impurities. The roughness has been measured by scanning force microscopy on an area of 20 microns x 20 microns on each sample. Polished titanium is smooth (peak-to-valley roughness 81 nm), whereas the acid-attacked surfaces exhibit a micro-roughness in the microns range (2100 nm for polished and acid attacked; 3600 nm for sandblasted and acid attacked) which is quite reproducible over large areas of the sample. The acid attacked samples present a subsurface layer which contains hydrogen below the native passivating oxide layer. Water wettability measurement shows that all surfaces are hydrophobic with a slightly higher contact angle for the acid attacked surfaces. The different treatments analyzed in this study essentially influence the surface roughness by preserving the chemical composition and the wettability properties of titanium native oxide surface layer.


Assuntos
Titânio/química , Polimento Dentário , Ácido Clorídrico/farmacologia , Hidrogênio/análise , Teste de Materiais , Microscopia Eletrônica , Óxidos/análise , Oxigênio/análise , Ácidos Sulfúricos/farmacologia , Propriedades de Superfície/efeitos dos fármacos , Molhabilidade
19.
Clin Oral Implants Res ; 8(3): 217-25, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9586466

RESUMO

The influence of titanium surface properties on in vitro adsorption isotherms of fibronectin, promotion of Staphylococcus aureus adhesion, and binding of a monoclonal antibody to the cell-binding domain of fibronectin was examined. Treatments producing different surface roughness were applied to a single side of commercially pure titanium coverslips, which was either mechanically polished (P), or polished and then acid attacked with H2SO4/HCl (PA), or sandblasted and then acid attacked (SLA), whereas the untreated side was blocked by an albumin coating layer. Incubation of the coverslips with concentrations of soluble 3H-labelled fibronectin increasing from 1 to 16 micrograms/ml led to the saturation of all surfaces with immobilized protein from 4 to 16 micrograms/ml. Promotion of S. aureus adhesion by fibronectin adsorbed on all surfaces and binding of the monoclonal antibody to its cell-binding domain was to some extent proportional to the amount of immobilized protein but also showed some minor differences between surfaces. More important material-related differences were observed when fibronectin adsorption isotherms were expressed as a function of the effective, roughness-corrected surface area, yielding amounts of immobilized fibronectin on the rough PA and SLA titanium surfaces which were 50% lower than those adsorbed on either smooth P or polymethylmethacrylate coverslips used as controls. In conclusion, surface treatments increasing the surface roughness of titanium do not increase, but may partly decrease in vitro adsorption of fibronectin. Despite adsorbing different amounts of fibronectin, both rough and smooth titanium surfaces promote normal expression of 2 major functional domains of this protein.


Assuntos
Titânio/química , Adsorção , Sequência de Aminoácidos , Aderência Bacteriana , Moléculas de Adesão Celular/metabolismo , Fibronectinas/química , Fibronectinas/metabolismo , Teste de Materiais , Microscopia Eletrônica de Varredura , Staphylococcus aureus/fisiologia , Propriedades de Superfície
20.
Br J Cancer ; 75(12): 1831-5, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9192990

RESUMO

Cytogenetic investigation was performed on direct preparations of 15 endometrial cancers showing different histotypes. Clonal abnormalities were found in 11 out of 13 analysable cases. The modal chromosome number was near diploid in all cases. The abnormal karyotypes contained relatively simple numerical or structural aberrations in the majority of tumours. In contrast, two neoplasms with serous papillary and mixed mullerian morphological features shared multiple complex changes as well as cytogenetic evidence of intratumoral heterogeneity. The most frequent chromosome abnormality in our series of endometrial neoplasms was 6q deletion, which was detected in serous papillary, endometrioid and mixed mullerian tumours. The loss of the 6q region, which is also frequently involved in ovarian carcinoma, suggests a relationship between endometrial and ovarian cancers based on a common histogenesis.


Assuntos
Adenocarcinoma/genética , Carcinoma Endometrioide/genética , Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Cistadenocarcinoma Papilar/genética , Neoplasias do Endométrio/genética , Neoplasias Ovarianas/genética , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Diploide , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Pessoa de Meia-Idade
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