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1.
Med Oral Patol Oral Cir Bucal ; 24(5): e621-e629, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433396

RESUMO

BACKGROUND: This study aimed to analyze the efficacy of an anti-calculus mouth rinse and its possible adverse effects on the mucosa and teeth. MATERIAL AND METHODS: This randomized double-blind placebo-controlled clinical trial included 40 patients with treated and managed periodontal disease, all with a history of rapid calculus formation. Patients used a pyrophosphate-based test mouth rinse (B) or a placebo (A). A range of parameters were measured for: saliva (saliva flow, pH and chemical composition); calculus (Volpe-Manhold [V-M] index, weight, and volume); adverse effects on mucosa and teeth; and the patients' subjective perceptive of mouth rinse efficacy. RESULTS: the test mouth rinse B produced reductions in urea, uric acid, and phosphorous, calcium, saliva flow, and increases in pH. V-M index and calculus weight decreased after using the test mouth rinse. Calculus volume decreased with both mouth rinses. No changes to the mucosa or teeth were observed. Patients perceived that the test mouth rinse was more effective. CONCLUSIONS: The test/B and placebo mouth rinses both modified certain parameters in saliva composition, particularly reductions in urea, uric acid, and phosphorous. Calcium tended to increase after using the test-B mouth rinse. The results did not demonstrate the anticalculus efficacy of the pyrophosphate-based mouth rinse or positive effects on saliva flow or composition. This field requires further research, as no product has been developed that prevents calculus formation completely.


Assuntos
Dentifrícios , Antissépticos Bucais , Cálculos Dentários , Difosfatos , Método Duplo-Cego , Humanos
2.
J Clin Pharm Ther ; 43(5): 714-716, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29722038

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Abiraterone acetate (AA) is an androgen receptor axis inhibitor, indicated together with prednisone, for metastatic castration-resistant prostate cancer. Withdrawal syndrome for classical antiandrogen treatments is well known, but not so known for AA. Abiraterone withdrawal syndrome (AWS) could be related to simultaneous prednisone discontinuation or to an androgenic effect of AA metabolites. CASE DESCRIPTION: A case is described of a patient with long-term AWS without prednisone discontinuation. The clinical and prostate-specific antigen (PSA) response allowed an 8-month delay in docetaxel treatment. WHAT IS NEW AND CONCLUSION: Prednisone did not play a role in AWS in this case. The long-term response allowed a delay in future treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Síndrome de Abstinência a Substâncias/etiologia , Acetato de Abiraterona/administração & dosagem , Acetato de Abiraterona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Humanos , Masculino , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Resultado do Tratamento
3.
Ann Oncol ; 28(7): 1508-1516, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28472366

RESUMO

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).


Assuntos
Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Benzamidas , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Análise Mutacional de DNA , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Análise Multivariada , Mutação , Nitrilas , Razão de Chances , Seleção de Pacientes , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Medicina de Precisão , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/mortalidade , Receptores Androgênicos/genética , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
4.
J Anat ; 225(5): 492-501, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25181319

RESUMO

Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration following laryngeal nerve injury, with subsequent application to humans.


Assuntos
Astrócitos/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Bulbo/metabolismo , Traumatismos do Nervo Laríngeo Recorrente/patologia , Animais , Apoptose , Proliferação de Células , Denervação , Masculino , Regeneração Nervosa , Ratos Sprague-Dawley , Traumatismos do Nervo Laríngeo Recorrente/metabolismo
5.
Ann Oncol ; 24(9): 2409-14, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23788753

RESUMO

BACKGROUND: Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib. RESULTS: High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023). CONCLUSIONS: We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Hipóxia Celular/efeitos dos fármacos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Indóis/efeitos adversos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Pirróis/efeitos adversos , RNA Mensageiro/biossíntese , Sunitinibe , Sobrevida , Resultado do Tratamento , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
J Nanosci Nanotechnol ; 12(12): 9148-55, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23447970

RESUMO

The growth of Anatase nanostructured films using dc reactive magnetron sputtering and post-annealing treatment is reported. TiO2 has been deposited on Porous Anodic Alumina Films used as templates which were previously grown in phosphoric acid solution and etched to modify their pore diameters. This synthesis via results in the formation of vertically aligned and spatially ordered TiO2 nanostructures replicating the underlying template. Previously, the growth optimization of TiO2 thin films deposited by dc magnetron sputtering on flat silicon substrates was done. The crystalline structure and Ti in-depth concentration profile were determined by grazing incidence X-ray diffraction and Rutherford backscattering spectrometry, respectively. The surface morphology of the samples was explored by mean of a Field Emission Gun scanning electron microscope. Optical properties of the nanostructured samples were studied by using the reflectance spectra received in the UV-visible range. In these spectra different band gap values and complex light absorption features were observed.

7.
Biomed Chromatogr ; 26(6): 769-74, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22002332

RESUMO

Pizotifen malate is an antihistamine and serotonin inhibitor used in the preventive treatment of migraine and eating disorders. A simple, rapid, accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection was validated for the quantitative analysis of pizotifen malate in samples from in vitro transdermal diffusion studies. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantification and robustness. Drug stability in the solution was also determined under different conditions. Separation was carried out using a 250 × 4.0 mm Kromasil(®) C(18) column at room temperature. The detector response, fitted at 254 nm, was found to be linear in a concentration range between 0.24 and 24.0 µg/mL. The limit of detection was 0.02 µg/mL and the limit of quantification was 0.07 µg/mL. Finally, in vitro transdermal diffusion of pizotifen malate was characterized using the validated HPLC method.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Pizotilina/análise , Pele/metabolismo , Administração Cutânea , Animais , Difusão , Cultura em Câmaras de Difusão , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Pizotilina/administração & dosagem , Pizotilina/química , Reprodutibilidade dos Testes , Absorção Cutânea , Suínos
8.
Environ Pollut ; 314: 120105, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36089148

RESUMO

Particulate matter from wood burning emissions (Cwood) was quantified at five locations in the United Kingdom (UK), comprising three rural and two urban sites between 2009 and 2021. The aethalometer method was used. Mean winter Cwood concentrations ranged from 0.26 µg m-3 (in rural Scotland) to 1.30 µg m-3 (London), which represented on average 4% (in rural environments) and 5% (urban) of PM10 concentrations; and 8% of PM2.5. Concentrations were greatest in the evenings in winter months, with larger evening concentrations in the weekends at the urban sites. Random-forest (RF) machine learning regression models were used to reconstruct Cwood concentrations using both meteorological and temporal explanatory variables at each site. The partial dependency plots indicated that temperature and wind speed were the meteorological variables explaining the greatest variability in Cwood, with larger concentrations during cold and calm conditions. Peaks of Cwood concentrations took place during and after events that are celebrated with bonfires. These were Guy Fawkes events in the urban areas and on New Year's Day at the rural sites; the later probably related to long-range transport. Time series were built using the RF. Having removed weather influences, long-term trends of Cwood were estimated using the Theil Sen method. Trends for 2015-2021 were downward at three of the locations (London, Glasgow and rural Scotland), with rates ranging from -5.5% year-1 to -2.5% year-1. The replacement of old fireplaces with lower emission wood stoves might explain the decrease in Cwood especially at the urban sites The two rural sites in England observed positive trends for the same period but this was not statistically significant.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , Madeira/química , Fatores Sociais , Monitoramento Ambiental , Tempo (Meteorologia) , Estações do Ano
9.
NanoImpact ; 28: 100437, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36332901

RESUMO

Plastic pollution represents an emerging environmental issue in terrestrial Antarctica, especially in the Antarctic Peninsula and Maritime Antarctica, which have been recently recognized as hot spots for plastic litter. In these regions, freshwater (FW) environments such as lakes host isolated ecosystems and species that can be severely affected by increasing environmental and anthropogenic stressors, which include plastics that are still overlooked. In this study, we investigated for the first time the impact of nanoplastics on adults of the fairy shrimp Branchinecta gaini (Order Anostraca) populating Antarctic FW ecosystems, using surface charged polystyrene nanoparticles (PS NPs) as a proxy. Short-term acute toxicity (48 h) was investigated by exposing adults to carboxyl (-COOH, 60 nm) and amino-modified (-NH2, 50 nm) PS NPs at 1 and 5 µg mL-1. Biodisposition of PS NPs and lethal and sub-lethal effects (i.e., swimming, moulting, histology, gene expression) were assessed. Behaviour of PS NPs in Antarctic FW media was monitored through 48 h of exposure showing that both PS NPs kept their nanoscale size in the Antarctic FW media. Survival of fairy shrimp adults over short-term exposure was not affected, on the other hand an increase in moulting rate and alterations in the gut epithelium were observed upon exposure to both PS NPs. Significant alterations at the behavioural (ventilation rate) and molecular (up-regulation of Hsp70mit, Hsp83, Sod, P450) levels were related to PS NP surface charge and associated with PS-NH2 exposure only. Nanoplastics could represent a threat for Antarctic FW biodiversity and the Antarctic fairy shrimp could be a valuable model for assessing their impact on such remote and pristine aquatic ecosystems.


Assuntos
Anostraca , Poliestirenos , Animais , Poliestirenos/toxicidade , Ecossistema , Regiões Antárticas
10.
Ann Oncol ; 22(1): 139-144, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20603439

RESUMO

BACKGROUND: neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients. PATIENTS AND METHODS: we assessed BRCA1 messenger RNA expression levels in paraffin-embedded pre-treatment tumor samples obtained by transurethral resection from 57 patients with locally advanced bladder cancer subsequently treated with neoadjuvant cisplatin-based chemotherapy. BRCA1 levels were divided into terciles and correlated with pathological response and survival. RESULTS: a significant pathological response (pT0-1) was attained in 66% (24 of 39) of patients with low/intermediate BRCA1 levels compared with 22% (4 of 18) of patients with high BRCA1 levels (P = 0.01). Median survival was 168 months in patients with low/intermediate levels and 34 months in patients with high BRCA1 levels (P = 0.002). In the multivariate analysis for survival, only BRCA1 expression levels and lymphovascular invasion emerged as independent prognostic factors. CONCLUSIONS: our data suggest that BRCA1 expression may predict the efficacy of cisplatin-based neoadjuvant chemotherapy and may help to customize therapy in bladder cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/biossíntese , RNA Mensageiro/biossíntese , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Inclusão em Parafina , RNA Mensageiro/genética , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/cirurgia , Vimblastina/administração & dosagem
11.
J Med Genet ; 47(4): 262-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19797195

RESUMO

BACKGROUND: Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive disorder characterised by the five cardinal features retinitis pigmentosa, postaxial polydactyly, mental retardation, obesity and hypogenitalism. In addition, renal cysts and other anomalies of the kidney and urinary tract can be present. To date, mutations in 12 BBS genes as well as in MKS1 and CEP290 have been identified as causing BBS. The vast genetic heterogeneity of BBS renders molecular genetic diagnosis difficult in terms of the time and cost required to screen all 204 coding exons. METHOD: Here, the use of genome-wide homozygosity mapping as a tool to identify homozygous segments at known BBS loci, in BBS individuals from inbred and outbred background, is reported. RESULTS: In a worldwide cohort of 45 families, causative homozygous mutations in 20 families were identified via direct exon sequencing. Eleven of these mutations were novel, thereby increasing the number of known BBS mutations by 5% (11/218). CONCLUSIONS: Thus, in the presence of extreme genetic locus heterogeneity, homozygosity mapping provides a valuable approach to the molecular genetic diagnosis of BBS and will facilitate the discovery of novel pathogenic mutations.


Assuntos
Síndrome de Bardet-Biedl/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico/métodos , Estudos de Coortes , Consanguinidade , Estudos de Associação Genética , Genoma Humano , Homozigoto , Humanos , Dados de Sequência Molecular , Fenótipo , Proteínas/genética
12.
Environ Int ; 136: 105411, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31889555

RESUMO

Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m2/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health.


Assuntos
Microplásticos , Poluentes Químicos da Água , Atmosfera , Monitoramento Ambiental , Humanos , Londres
13.
J Healthc Qual Res ; 35(2): 95-101, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32241728

RESUMO

BACKGROUND AND OBJECTIVES: The elderly patient is particularly vulnerable to potentially inappropriate prescription (PIP) due to physiological reasons, comorbidity, polypharmacy or the different pharmacokinetics/pharmacodynamics of drugs. The aim of this study was to determine the prevalence of PIP according to the STOPP-START criteria in patients over 65 years admitted into a geriatric hospital, as well as to appraise its acceptance by geriatricians. MATERIAL AND METHODS: Retrospective observational study. Patients older than 65 years consecutively admitted to medium/long-stay units were included. The study information was obtained by reviewing the clinical record of the patients. The PIP according to the STOPP-START criteria were assessed by the geriatrician, who decided whether or not to modify the medication and recorded the reasons. RESULTS: 247 patients were included, mean age was 82.6 years (SD 7.3), 72.1% of patients were female and a median of 7 drugs (25-75 percentile: 4-9). 78.9% (95%CI: 73.3-83.9) of patients had at least one PIP STOPP-START at admission, 44.9% (95%CI: 38.6-51.4) PIP-STOPP and 59.5% (95%CI: 53.1-65.7) PIP-START. At hospital discharge, the prevalence of PIP-STOPP-START was 46.2% (95%CI: 39.8-52.6), 19.0% (95%CI: 14.3-24.5) of PIP-STOPP and 34.4% (95%CI: 28.5-40.7) PIP-START. CONCLUSIONS: The comprehensive geriatric assessment and the use of the STOPP-START criteria can significantly reduce the prevalence of PIP among patients admitted to a geriatric hospital. Nevertheless, issues such as frailty, multimorbidity and functional goals would be taken into account in the appropriateness of the prescription.


Assuntos
Prescrições de Medicamentos/normas , Hospitalização , Prescrição Inadequada/estatística & dados numéricos , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Feminino , Avaliação Geriátrica , Geriatras/psicologia , Hospitais Especializados , Humanos , Masculino , Estudos Retrospectivos
14.
Br J Cancer ; 101(8): 1248-52, 2009 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-19755998

RESUMO

BACKGROUND: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. METHODS: Patients with T1c-T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml(-1) and/or Gleason score >or=7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m(-2) on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). RESULTS: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was >or=7 (4+3) in 44 (77%) patients and PSA >20 ng ml(-1) in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. CONCLUSION: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Idoso , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias da Próstata/patologia , Taxoides/administração & dosagem
15.
J Inherit Metab Dis ; 32 Suppl 1: S339-43, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19924563

RESUMO

Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the PDHA1 gene which encodes the E(1)α subunit, with few cases of mutations in the genes for E(3), E3BP (E(3) binding protein), E(2) and E(1)-phosphatase being reported. Only seven patients with deficiency of the E(1)ß subunit have been described, with mutations in the PDHB gene in six of them. Clinically they presented with a non-specific encephalomyopathy. We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E(1) activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. Sequencing of PDHB revealed a homozygous point mutation (c.302T>C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). All three mutations appear to destabilize the E(1) enzyme with a decrease of both E(1)α and E(1)ß subunits in immunoblot analysis. To our knowledge, these patients with novel PDHB mutations are the first reported with Leigh syndrome.


Assuntos
Doença de Leigh/enzimologia , Mutação Puntual , Piruvato Desidrogenase (Lipoamida)/deficiência , Piruvato Desidrogenase (Lipoamida)/genética , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Triagem de Portadores Genéticos , Homozigoto , Humanos , Lactente , Recém-Nascido , Doença de Leigh/diagnóstico , Doença de Leigh/genética , Masculino , Dados de Sequência Molecular
17.
J Phys Condens Matter ; 31(29): 295703, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30978705

RESUMO

Chemically-driven isothermal close space vapour transport was used to prepare pure MoO2 thin films which were eventually converted to MoO3 by annealing in air. According to temperature-dependent Raman measurements, the MoO2/MoO3 phase transformation was found to occur in the 225 °C-350 °C range while no other phases were detected during the transition. A clear change in composition as well as noticeable modifications of the band gap and the absorption coefficient confirmed the conversion from MoO2 to MoO3. An extensive characterization of these two pure phases was carried out. In particular, a procedure was developed to determine the dispersion relation of the refractive index of MoO2 from the shift of the interference fringes of the used SiO2/Si substrate. The obtained data of the refractive index was corrected taking into account the porosity of the samples calculated from elastic backscattering spectrometry. The Debye temperature and the residual resistivity were extracted from the electrical resistivity temperature dependence using the Bloch-Grüneisen equation. MoO3 converted samples presented a very high resistivity and a typical semiconducting behavior. They also showed intense and broad luminescence spectra composed by several contributions whose temperature behavior was examined. Furthermore, surface photovoltage spectra were taken and their relation with the photoluminescence is discussed.

18.
J Pharm Sci ; 97(6): 2102-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17854062

RESUMO

We have successfully obtained sumatriptan transdermal systems with different polymer compositions: methyl cellulose (MC), polyvinyl pyrrolidone (PVP) and a polyvinyl pyrrolidone (PVP)-polyvinyl alcohol (PVA) mixture. The systems contained 1,2-propylenglycol (MC) or sorbitol as a plasticizer (PVP and PVP-PVA), methacrylate copolymer as an adhesive agent, and an occlusive liner. Azone (5%, w/w) was incorporated into all the systems as a percutaneous enhancer. Transdermal systems are thin, transparent and non-adhesive when in a dry state. The permeation of sumatriptan succinate across pig ear skin was studied using the systems prepared. The formulation with MC polymer produced a statistically significant increment with respect to the PVP and PVP-PVA formulations (p < 0.05). Azone incorporation into the systems produced an increment in the sumatriptan flux values of all three transdermal systems with respect to those of the controls (p < 0.05). In addition, the application of iontophoresis to the wet methyl cellulose-Azone formulation produced a much higher increase of sumatriptan transdermal flux.


Assuntos
Portadores de Fármacos , Transtornos de Enxaqueca/tratamento farmacológico , Polímeros/química , Agonistas do Receptor de Serotonina/administração & dosagem , Sumatriptana/administração & dosagem , Vasoconstritores/administração & dosagem , Administração Cutânea , Animais , Azepinas/química , Química Farmacêutica , Cultura em Câmaras de Difusão , Composição de Medicamentos , Iontoforese , Cinética , Metilcelulose/química , Permeabilidade , Plastificantes/química , Ácidos Polimetacrílicos/química , Álcool de Polivinil/química , Povidona/química , Propilenoglicol/química , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/metabolismo , Pele/metabolismo , Absorção Cutânea , Sorbitol/química , Sumatriptana/química , Sumatriptana/metabolismo , Suínos , Tecnologia Farmacêutica/métodos , Adesivos Teciduais/química , Vasoconstritores/química , Vasoconstritores/metabolismo
19.
Oper Dent ; 43(5): 482-487, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513640

RESUMO

OBJECTIVES: To evaluate the clinical behavior of one-piece complete-coverage crowns and fixed partial dentures (FPDs) on teeth with vertical preparation without finish line biologically oriented preparation technique (BOPT). METHODS AND MATERIALS: This prospective study included 52 patients requiring treatment with restorations in the esthetic region: 74 crowns and 27 FPDs. The sample included a total of 149 teeth that were prepared vertically without finish line. The sample was divided into two groups: one-piece crowns and FPDs, all with zirconia cores, feldspathic ceramic veneer, and a 0.5-mm prosthetic finish line of zirconia. All procedures were carried out at the University of Valencia from 2013 to 2014. The following parameters were evaluated over a two-year follow-up: oral hygiene, periodontal state, gingival thickening, gingival margin stability, the presence of complications, and restoration survival rate. Patient satisfaction with treatment was assessed by means of a visual analogue scale (VAS). RESULTS: Two years after treatment, 80.5% of treated teeth remained free of gingival inflammation and bleeding. Mean gingival thickening was 0.41 ± 0.28 mm for one-piece crowns and 0.38 ± 0.36 mm for FPDs. Gingival margin stability was 100%, but 2% of the sample presented biological complications. The VAS patient satisfaction scores were eight out of a maximum score of 10. CONCLUSIONS: Two years after treatment, vertical preparation without finish line produces gingival thickening, margin stability, and optimal esthetics. Neither crowns nor FPDs presented any mechanical complications.


Assuntos
Coroas , Restauração Dentária Permanente/métodos , Doenças da Gengiva/etiologia , Zircônio/uso terapêutico , Adolescente , Adulto , Idoso , Cerâmica/efeitos adversos , Cerâmica/uso terapêutico , Coroas/efeitos adversos , Restauração Dentária Permanente/efeitos adversos , Estética Dentária , Feminino , Seguimentos , Gengiva/efeitos dos fármacos , Doenças da Gengiva/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Adulto Jovem , Zircônio/efeitos adversos
20.
J Neurol Neurosurg Psychiatry ; 78(12): 1392-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17615167

RESUMO

OBJECTIVE: To determine clinical variables related to recurrent lacunar infarction following a previous lacunar stroke. METHODS: A total of 122 out of 733 consecutive patients with lacunar infarction collected from a hospital based registry between 1986 and 2004 were readmitted because of a recurrent lacunar infarction. In a subset of 59 patients, cognition was assessed using the Mini-Mental State Examination (MMSE). Predictors of lacunar infarction recurrence were assessed by logistic regression analysis. RESULTS: First lacunar infarction recurrence occurred in 101 patients (83%) and multiple recurrences in 21. The mean time between first ever lacunar infarction and recurrent lacunes was 58.3 months (range 2-240). In the subset of 59 patients in whom cognition was studied, cognitive impairment, defined as an MMSE score <24, was detected in 16% (8/49) of patients with first lacunar infarction recurrence and in 40% (4/10) of those with multiple lacunar infarction recurrences. In the multivariate analysis, hypertension (odds ratio 2.01, 95% CI 1.23 to 3.30) and diabetes (odds ratio 1.62, 95% CI 1.07 to 2.46) were significant predictors of lacunar stroke recurrence, whereas hyperlipidaemia was inversely associated (odds ratio 0.52, 95% CI 0.30 to 0.90). CONCLUSIONS: Hypertension and diabetes were significant factors related to recurrent lacunar infarction. Hyperlipidaemia appeared to have a protective role. Cognitive impairment was a frequent finding in patients with multiple lacunar infarction recurrences.


Assuntos
Infarto Encefálico/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Área Programática de Saúde , Circulação Cerebrovascular/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Avaliação da Deficiência , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Testes Neuropsicológicos , Recidiva , Sistema de Registros , Índice de Gravidade de Doença , Espanha/epidemiologia
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