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1.
J Endocrinol Invest ; 45(7): 1349-1358, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35226335

RESUMO

PURPOSE: Patients with hereditary hypophosphatemic rickets are short and disproportionate and very little information is available on segmental growth, but the body disproportion at adulthood leads us to think that the growth velocity of legs is slower. METHODS: A total of 96 children were included and molecular testing was carried out in 42. Children who reached adult height were classified into two groups according to their compliance to conventional treatment (phosphate supplement and calcitriol). Individual growth records of height and sitting height/height were plotted using Argentine reference data in 96 children and growth curves were estimated by fitting Preece-Baines Model 1 in 19 of the children. RESULTS: Molecular testing revealed sequence deleterious alterations or large deletions in 36/42 patients. During childhood, 76% of children grew below - 1.88 standard deviation score (SDS) and 97% had body disproportion. During adolescence, the mean peak height velocity for the good and poor compliance to treatment groups was 7.8 (0.6) and 5.4 (0.4) cm/year in boys and 7.0 (0.7) and 5.2 (0.8) cm/year in girls, respectively. At adulthood, the median sitting height/height ratio was 2.32 and 6.21 SDS for the good and poor compliance to treatment groups, respectively. The mean pubertal growth spurt of the trunk was -0.8 (1.4) SDS, with a short pubertal growth spurt of - 1.8 (0.4) SDS for limbs in the good compliance group. Median adult height in 13/29 males and 30/67 females was -4.56 and -3.16 SDS, respectively. CONCLUSION: For all patients the growth spurt was slower, secondary to a short growth spurt of limbs, reaching a short adult height with body disproportion that was more prominent in the poor compliance group.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Adolescente , Adulto , Estatura , Calcitriol , Criança , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Humanos , Masculino , Fosfatos , Puberdade , Estudos Retrospectivos
2.
Ann Hum Biol ; 48(1): 8-14, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33533281

RESUMO

Background: Children with achondroplasia (ACH) appear to lack a pubertal growth spurt in height.Aim To explore the growth spurt in height and its segments sitting height and leg length, in a large sample of ACH cases using growth curve modelling.Subjects and methods: Height and sitting height were measured longitudinally in ACH children, and the data were analysed using the SITAR (SuperImposition by Translation and Rotation) growth model, which estimates a mean growth curve and random effects for individuals defining differences in size, pubertal timing and intensity.Results: Out of 402 ACH children, 85 boys and 75 girls aged 7-20 years had respectively 529 and 454 measurements of height and sitting height, with leg length calculated by difference. SITAR analysis identified peaks in mean height velocity at 13.3 and 11.3 years in boys and girls, with peak velocities of 4.3 and 4.4 cm/year. Mean peak velocity for sitting height was 3.0 cm/year, but leg length showed no peak. The SITAR models explained 92% to 99% of the cross-sectional variance.Conclusion: ACH children do experience a growth spurt in puberty, but only half that of control children. The spurt is due entirely to sitting height, with no leg length spurt.


Assuntos
Acondroplasia/fisiopatologia , Estatura/fisiologia , Crescimento , Perna (Membro)/fisiologia , Puberdade , Postura Sentada , Adolescente , Argentina , Criança , Feminino , Humanos , Masculino
4.
BJOG ; 124(3): 495-502, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27506510

RESUMO

OBJECTIVE: To evaluate whether colposcopic measurement of the lesion size at diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in women treated for squamous intraepithelial lesions/cervical intraepithelial neoplasia (SIL/CIN). DESIGN: Prospective observational study. SETTING: Tertiary university hospital. POPULATION: A cohort of 116 women who underwent LLETZ because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or because of a high-grade SIL/CIN diagnosed in the referral visit and squamocolumnar junction completely visible (types 1 or 2, according to the International Federation of Cervical Pathology and Colposcopy, IFCPC). METHODS: After LLETZ the women were classified by histology into the study group (absence of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group (SIL/CIN in the LLETZ specimen, 88/116, 75.9%). MAIN OUTCOME MEASURES: The size of the lesion determined in the diagnostic colposcopy and the HPV genotype were evaluated in all women. RESULTS: The lesion size was significantly smaller in the study group (25.7 ± 37.8 versus 84.5 ± 81.7 mm2 ; P < 0.001). A lesion size of ≤12 mm2 and HPV types other than 16 or 18 were associated with an absence of SIL/CIN in the LLETZ specimen (P < 0.001 and P = 0.016, respectively). On multivariate analysis only a lesion size of ≤12 mm2 predicted the absence of SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P < 0.001). A lesion size of ≤12 mm2 had a specificity of 90.9% (95% CI 83.0-95.3%) and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the absence of SIL/CIN in the surgical specimen. CONCLUSIONS: Small lesion size in diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen. Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary treatment. TWEETABLE ABSTRACT: Small lesion size in colposcopic evaluation might predict the absence of SIL/CIN in an LLETZ specimen.


Assuntos
Colposcopia/métodos , Testes de DNA para Papilomavírus Humano/métodos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colo do Útero/patologia , Colo do Útero/cirurgia , Feminino , Seguimentos , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Estudos Prospectivos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia
5.
BJOG ; 124(9): 1356-1363, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28391609

RESUMO

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.


Assuntos
DNA Viral/urina , Autoavaliação Diagnóstica , Teste de Papanicolaou , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Adolescente , Adulto , Biomarcadores/urina , Colposcopia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/urina , Estudos Prospectivos , Sensibilidade e Especificidade , Triagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/urina , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/urina , Displasia do Colo do Útero/virologia
6.
J Nat Prod ; 79(2): 261-6, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26797293

RESUMO

Several preparations were obtained from the aerial parts of predomesticated Lavandula luisieri, including the essential oil and ethanolic, hexane, and ethyl acetate extractives. Additionally, pilot plant vapor pressure extraction was carried out at a pressure range of 0.5-1.0 bar to give a vapor pressure oil and an aqueous residue. A chemical study of the hexane extract led to the isolation of six necrodane derivatives (1, 2, and 4-7), with four of these (1, 2, 5, and 7) being new, as well as camphor, a cadinane sesquiterpene (9), tormentic acid, and ursolic acid. The EtOAc and EtOH extracts contained a mixture of phenolic compounds with rosmarinic acid being the major component. Workup of the aqueous residue resulted in the isolation of the necrodane 3 and (1R*,2S*,4R*)-p-menth-5-ene-1,2,8-triol (8), both new natural compounds. The structures of the new compounds were established based on their spectroscopic data. The phytotoxic and nematicidal activities of these compounds were evaluated.


Assuntos
Antinematódeos/isolamento & purificação , Antinematódeos/farmacologia , Terpenos/isolamento & purificação , Terpenos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antinematódeos/química , Afídeos/efeitos dos fármacos , Lavandula/química , Estrutura Molecular , Monoterpenos , Ressonância Magnética Nuclear Biomolecular , Óleos Voláteis/análise , Componentes Aéreos da Planta/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Espanha , Spodoptera/efeitos dos fármacos , Terpenos/química , Triterpenos/isolamento & purificação , Ácido Ursólico
7.
Eur J Gynaecol Oncol ; 37(1): 26-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27048105

RESUMO

PURPOSE OF INVESTIGATION: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous ovarian cancer (MOC). MATERIALS AND METHODS: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC. RESULTS: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125. CONCLUSIONS: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/análise , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Adulto Jovem
8.
BJOG ; 122(1): 119-27, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25229645

RESUMO

OBJECTIVE: Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity. DESIGN: Observational study. SETTING: Barcelona, Spain. POPULATION: A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing. METHODS: All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay). MAIN OUTCOME MEASURES: Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups. RESULTS: Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality. CONCLUSIONS: An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , DNA Viral/genética , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adenocarcinoma Mucinoso/virologia , Adulto , Idoso , Carcinoma Adenoescamoso/virologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Prognóstico , Neoplasias do Colo do Útero/virologia
9.
Gynecol Oncol ; 135(2): 201-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25204846

RESUMO

OBJECTIVE: It has been suggested that colposcopy can miss a significant percentage of high-grade cervical intraepithelial neoplasia (CIN2+). Improved disease ascertainment was evaluated by taking multiple lesion-directed biopsies. METHODS: In a cross-sectional multicenter study in the Netherlands and Spain, 610 women referred to colposcopy following abnormal cervical cytology results were included. Multiple directed biopsies were collected from lesions and ranked according to impression. A non-directed biopsy of normal-appearing tissue was added if fewer than four biopsies were collected. We evaluated the additional CIN2+ yield for one and two directed biopsies. Colposcopic images were reviewed for quality control. RESULTS: In women with at least two lesion-directed biopsies the yield for CIN2+ increased from 51.7% (95%CI; 45.7-57.7) for one directed biopsy to 60.4% (95%CI; 54.4-66.2, p<0.001) for two biopsies. The highest CIN2+ yield was observed in women who were HPV16-positive, had high-grade squamous intraepithelial lesion (HSIL) cytology, and high-grade colposcopy impression. The yield increased from 83.1% (95%CI; 71.5-90.5) with one directed biopsy to 93.2% (95%CI; 83.8-97.3) with two directed biopsies. Only 4.5% additional CIN2+ were detected in biopsies not targeting abnormal areas on the cervix. CONCLUSIONS: A second lesion-directed biopsy is associated with a significant increase in CIN2+ detection. Performing a second lesion-directed biopsy and using a low threshold for abnormality of any acetowhitening should become the standard clinical practice of colposcopy.


Assuntos
Colo do Útero/patologia , Colposcopia/métodos , Infecções por Papillomavirus/patologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Estudos Transversais , DNA Viral/genética , Feminino , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/complicações , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/diagnóstico
10.
BJOG ; 121(9): 1117-26, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24494663

RESUMO

OBJECTIVE: To study colposcopic performance in diagnosing high-grade cervical intraepithelial neoplasia or cervical cancer (CIN2+ and CIN3+) using colposcopic characteristics and high-risk human papillomavirus (hrHPV) genotyping. DESIGN: Cross-sectional multicentre study. SETTING: Two colposcopy clinics in The Netherlands and Spain. POPULATION: Six hundred and ten women aged 17 years and older referred for colposcopy because of abnormal cytology. METHODS: A cervical smear was obtained. Colposcopists identified the worst lesion, graded their impression and scored the colposcopic characteristics of the lesions. Up to four biopsies were collected, including one biopsy from visually normal tissue. MAIN OUTCOME MEASURES: CIN2+ and CIN3+, positive for HPV16 or other high-risk HPV types (non-16 hrHPV-positive). RESULTS: The mean age in HPV16-positive CIN2+ women was 35.1 years compared with 39.1 years in women with other hrHPV types (P = 0.002). Sensitivity for colposcopy to detect CIN2+ was 87.9% (95%CI 83.2-91.5), using colposcopic cut-off of 'any abnormality'. The remaining CIN2+ were found by a biopsy from visually normal tissue or endocervical curettage (ECC). Detection of CIN2+ by lesion-targeted biopsies was not different between HPV16-positive women [119/135; 88.1% (95%CI 81.2-92.9)] and non-16 hrHPV-positive women [100/115; 87.0% (95%CI 79.1-92.3); P = 0.776]. In multivariate analysis, 'acetowhitening' [odds ratio (OR) 1.91, 95%CI 1.56-3.17], 'time of appearance' (OR 1.95, 95%CI 1.21-3.15) and 'lesion >25% of visible cervix' (OR 2.25, 95%CI 1.44-3.51) were associated with CIN2+. CONCLUSIONS: In this population following European screening practice, HPV16-related CIN2+ lesions were detected at younger age and showed similar colposcopic impression as non-16 hrHPV high-grade lesions. There was no relationship between any of the colposcopic characteristics and HPV16 status.


Assuntos
Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Alphapapillomavirus/genética , Colposcopia , Estudos Transversais , Feminino , Genótipo , Papillomavirus Humano 16/genética , Humanos , Países Baixos , Infecções por Papillomavirus/patologia , Sensibilidade e Especificidade , Espanha , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia
11.
J Pediatr Genet ; 13(3): 167-174, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39086440

RESUMO

Spondylocarpotarsal synostosis syndrome (SCT) is a very rare skeletal dysplasia characterized by vertebral, carpal, and tarsal fusion; growth retardation; and mild dysmorphic facial features. Variants in FLNB, MYH3, and RFLNA have been implicated in this dysplasia. We report the clinical and radiological follow-up of seven SCT pediatric cases associated with biallelic FLNB variants, from four Argentinian families. The seven cases share previously described facial characteristics: round facies, large eyes, and wide based nose; all of them had variable height deficit, in one case noted early in life. Other findings included clinodactyly, joint limitation without bone fusion, neurosensorial hearing loss, and ophthalmological compromise. All cases presented with spinal fusion with variable severity and location, carpal bones coalition, and also delay in carpal ossification. The heterozygous carrier parents had normal height values to -2.5 score standard deviation, without skeletal defects detected. Three different FLNB variants, one nonsense and two frameshift, were detected, all of which were predicted to result in a truncated protein or are degraded by nonsense mediated decay. All cases had at least one copy of the nonsense variant, c.1128C> G; p. (Tyr376*), suggesting the presence of a common ancestor.

12.
J Proteome Res ; 12(1): 112-22, 2013 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-23234512

RESUMO

The Chromosome 16 Consortium forms part of the Human Proteome Project that aims to develop an entire map of the proteins encoded by the human genome following a chromosome-centric strategy (C-HPP) to make progress in the understanding of human biology in health and disease (B/D-HPP). A Spanish consortium of 16 laboratories was organized into five working groups: Protein/Antibody microarrays, protein expression and Peptide Standard, S/MRM, Protein Sequencing, Bioinformatics and Clinical healthcare, and Biobanking. The project is conceived on a multicenter configuration, assuming the standards and integration procedures already available in ProteoRed-ISCIII, which is encompassed within HUPO initiatives. The products of the 870 protein coding genes in chromosome 16 were analyzed in Jurkat T lymphocyte cells, MCF-7 epithelial cells, and the CCD18 fibroblast cell line as it is theoretically expected that most chromosome 16 protein coding genes are expressed in at least one of these. The transcriptome and proteome of these cell lines was studied using gene expression microarray and shotgun proteomics approaches, indicating an ample coverage of chromosome 16. With regard to the B/D section, the main research areas have been adopted and a biobanking initiative has been designed to optimize methods for sample collection, management, and storage under normalized conditions and to define QC standards. The general strategy of the Chr-16 HPP and the current state of the different initiatives are discussed.


Assuntos
Cromossomos Humanos Par 16 , Bases de Dados de Proteínas , Proteínas , Proteoma/análise , Linhagem Celular , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/metabolismo , Expressão Gênica , Genoma Humano , Humanos , Espectrometria de Massas , Proteínas/classificação , Proteínas/genética , Proteínas/metabolismo , Transcriptoma
13.
BJOG ; 120(4): 392-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23189989

RESUMO

OBJECTIVE: To evaluate the feasibility and utility of intraoperative post-conisation human papillomavirus (IOP-HPV) testing and cytology to detect treatment failure in patients with cervical intraepithelial neoplasia grades 2-3 (CIN2-3). DESIGN: Prospective observational pilot study. SETTING: Barcelona, Spain. POPULATION: A cohort of 132 women treated for CIN2-3 by loop electrosurgical conisation. METHODS: An endocervical sample was obtained intraoperatively with a cytobrush from the cervix remaining after the conisation. The material was kept in PreservCyt medium and processed for Hybrid Capture 2 and cytology. Patients were followed-up for 24 months. The performance of IOP-HPV testing and IOP cytology was compared with conventional indicators of recurrence (cone margin, endocervical curettage, and HPV testing and cytology at 6 months). MAIN OUTCOME MEASURE: Treatment failure (i.e. recurrent CIN2-3 during follow-up). RESULTS: Treatment failure was identified in 12 women (9.1%). IOP-HPV testing for sensitivity, specificity, and positive and negative predictive values for treatment failure were 91.7, 78.3, 62.2, and 96.0%, respectively, which are similar to the figures for conventional HPV testing at 6 months (91.7, 76.0, 64.0, and 95.1%, respectively), and are better than the values of other conventional predictive factors (cone margin, endocervical curettage, and cytology intraoperative at 6 months). IOP-HPV was strongly associated with treatment failure in the multivariate analysis (OR 15.40, 95% CI 1.58-150.42). CONCLUSION: IOP-HPV testing is feasible, and accurately predicts treatment failure in patients with CIN2-3. This new approach may allow an early identification of patients with treatment failure, thereby facilitating the scheduling of an attenuated follow-up for negative patients who are at very low risk of persistent disease.


Assuntos
Colo do Útero/cirurgia , Conização/métodos , Eletrocirurgia/métodos , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Colposcopia/métodos , Detecção Precoce de Câncer/métodos , Estudos de Viabilidade , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Projetos Piloto , Estudos Prospectivos , Sensibilidade e Especificidade , Falha de Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
14.
Vaccine X ; 11: 100187, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35755140

RESUMO

Background: In December 2020, Sputnik V was incorporated to the National COVID-19 Immunization Plan in Argentina. Studies had shown 98% of antibody response rate. To date, data on immunogenicity and antibody persistence in Argentina are scarce.The objective was to assess humoral immune response after two doses of Sputnik V in Health Care Workers (HCWs) at the Ricardo Gutierrez Children's Hospital (RGCH). Methods: A prospective, cohort study in HCWs immunized with two doses of Sputnik V between February and March 2021. The following variables were assessed: age, gender, risk factors for severe COVID-19 or mortality, immunosuppressive therapy and history of SARS-CoV-2. Blood samples were drawn on the day of the first dose, 28 days and 180 days after the second. Anti-Spike IgG was measured using an ELISA assay. Differences in immune response were evaluated according to study variables. Comparison analyses between groups with or without history of infection were performed, with T-test and ANOVA or Mann-Whitney tests. For each subject, we compared baseline values with 28 days and 180 days after the second vaccine.STATA version 14 and R Sofware were used for data analyses. Results: We included 528 individuals, mean age 41.5 years, 82.9% female, 14.4% (76/528) reported previous SARS-CoV-2 infection.All subjects developed antibodies post-vaccination. At day 28, concentrations were significantly higher in previously infected than naïve subjects (p < 0.001) with no differences according to age, gender and comorbidities.At day 180, 17% (95% CI 13.17-21.53) of naïve subjects were negative. Antibody concentrations decreased significantly in all subjects except in those who reported SARS-CoV-2 infection after vaccination (n = 31). This last group had significantly higher antibody concentrations. Conclusion: This study assessed immune response to a new COVID-19 vaccine in real life in a cohort of subjects. Antibody concentrations varied according to history of SARS-COV-2 infection and decreased over time.

15.
Eur J Obstet Gynecol Reprod Biol ; 251: 23-27, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32480177

RESUMO

OBJECTIVE: The aim of this study was to evaluate the oncological outcomes of vaginal fertility-sparing surgery plus laparoscopic sentinel lymph node biopsy in patients with early cervical cancer over a 15-years period. PATIENTS AND METHODS: From March 2005 to April 2018, 38 patients diagnosed with early stage cervical cancer underwent vaginal fertility-sparing surgery at the Hospital Clínic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent radical vaginal trachelectomy. All cases underwent laparoscopic sentinel lymph node biopsy. In the first 19 cases, laparoscopic bilateral pelvic lymphadenectomy was completed immediately after sentinel lymph node biopsy. Clinical and oncological follow-up data were collected. RESULTS: The median age at diagnosis was 33.5 years (range 22-44). Simple trachelectomy was performed in seven cases (18.4%) and vaginal radical trachelectomy in 31 (81.6%). Nineteen patients were exclusively treated with laparoscopic sentinel lymph node biopsy and 19 with sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy. There were no significant differences between the two lymph node assessment groups regarding histology and tumour size. The median follow-up was 73 months (range 1-160 months). There were 4 recurrences (3 patients with IB1 and 1 with IA2). Two occurred in the sentinel lymph node biopsy group and 2 in the sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy group. All the recurrences were diagnosed in patients with adenocarcinoma and in 3 patients without lymphovascular space invasion. CONCLUSION: Vaginal fertility-sparing surgery combined with laparoscopic sentinel lymph node biopsy seems to be a safe oncological procedure in selected patients with early stage cervical cancer. Further studies are needed to clarify the role of sentinel lymph node biopsy in fertility- sparing surgery in cervical cancer. Adenocarcinoma histology seems to be an important risk factor for recurrence.


Assuntos
Laparoscopia , Linfonodo Sentinela , Neoplasias do Colo do Útero , Adulto , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Espanha , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
16.
Clin Transl Oncol ; 22(8): 1295-1302, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31865604

RESUMO

PURPOSE: To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. METHODS/MATERIAL: From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4-6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5-6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. STATISTICS: the chi-square test. RESULTS: The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. CONCLUSIONS: One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.


Assuntos
Braquiterapia , Fracionamento da Dose de Radiação , Neoplasias do Endométrio/radioterapia , Idoso , Braquiterapia/métodos , Distribuição de Qui-Quadrado , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Órgãos em Risco/efeitos da radiação , Período Pós-Operatório , Hipofracionamento da Dose de Radiação , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Vagina/efeitos da radiação
18.
Rev Neurol ; 68(4): 147-154, 2019 Feb 16.
Artigo em Espanhol | MEDLINE | ID: mdl-30741401

RESUMO

INTRODUCTION: The relationship between socioeconomic status and incidence or stroke mortality rates is well established. The evidence of an association between this variable and survival is less conclusive. Level of education is a widely-used measure of socioeconomic status in elderly people. AIM: To assess the relationship between one-year survival after stroke and level of education. PATIENTS AND METHODS: We analysed data on 544 consecutively recruited patients admitted for acute ischaemic stroke in one the public hospitals of Bizkaia (Spain). Data were obtained through interviews with patients or accompanying persons and from medical records. We studied variables concerning previous functional status, stroke severity, cardiovascular risk factors and stroke care provided. Patients were followed up for 12 months and the dates of any deaths were recorded. Univariate and multivariate analyses were carried out to assess the relationship between level of education and survival. RESULTS: A total of 203 (86%) women and 273 (88.6%) men were alive at 12 months. In both sexes, individuals with a lower level of education had poorer previous functional status, more severe strokes and higher mortality rates. In the multivariate analysis, the association between level of education and survival remained significant in the adjusted model in men. CONCLUSIONS: In our setting, there are differences in the survival of patients with ischaemic stroke as a function of level of education. The impact of this factor was greater in men than women.


TITLE: Relacion del nivel de estudios con la supervivencia en el primer año tras un ictus isquemico.Introduccion. La relacion del nivel socioeconomico con las tasas de incidencia y de mortalidad por ictus esta bien establecida. La evidencia de la relacion con la supervivencia de los pacientes tras el ictus es menos concluyente. El nivel educativo es una medida de nivel socioeconomico muy utilizada en estudios con personas de edad avanzada. Objetivo. Estudiar la relacion de la supervivencia en el primer año tras el ictus con el nivel de estudios. Pacientes y metodos. Se analizaron los datos de 544 pacientes con ictus isquemico agudo ingresados en los hospitales publicos de Bizkaia (España), seleccionados consecutivamente. Se obtuvieron datos por entrevista a pacientes o acompañantes y de historia clinica. Se estudiaron variables sobre situacion funcional previa, gravedad del ictus, factores de riesgo cardiovascular y de atencion al ictus. Se hizo un seguimiento de 12 meses para registrar, en su caso, la fecha de fallecimiento. Se realizo un analisis univariado y multivariado para identificar la relacion del nivel de estudios con la supervivencia. Resultados. Tras 12 meses, sobrevivian 203 mujeres (86%) y 273 hombres (88,6%). En ambos sexos, las personas con menos estudios tuvieron peor situacion funcional previa, mayor gravedad y fallecieron en mayor proporcion. En el analisis multivariado, el nivel de estudios se mantuvo asociado con la supervivencia en el modelo ajustado para los hombres. Conclusiones. La diversidad de nivel educativo marca diferencias en la supervivencia de los pacientes con ictus isquemico en nuestro entorno. El impacto de este factor fue mayor en los hombres que en las mujeres.


Assuntos
Isquemia Encefálica/mortalidade , Escolaridade , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida , Fatores de Tempo
19.
Parasite Immunol ; 30(5): 271-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18221450

RESUMO

Antigenic proteins of Echinostoma caproni (Trematoda) against mouse IgM, IgA, IgG, IgG1 and IgG2a were investigated by immunoproteomics. Excretory/secretory products (ESP) of E. caproni separated by two-dimensional (2D) gel electrophoresis were transferred to nitrocellulose membranes and probed with the different mouse immunoglobulin classes. A total of four proteins (enolase, 70 kDa heat-shock protein (HSP-70), actin and aldolase) were accurately identified. Enolase was recognized in eight different spots of which seven of them were detected in the expected molecular weight and were recognized by IgA, IgG or IgG and IgG1. Another spot identified as enolase at 72 kDa was only recognized by IgM. Digestion with N-glycosidase F of the 72 kDa band rendered a polypeptide with an apparent molecular weight similar to that expected for enolase recognized by Western immunoblotting using anti-enolase antibodies. This suggests that glycosylated forms of enolase may be involved in the early thymus-independent responses against E. caproni. Early IgM responses were also generated by actin and the HSP-70 which suggests that these proteins are exposed early to the host and may be of importance in the parasite establishment. The IgA responses also appear to be mediated by the HSP-70 and aldolase which could be related with the close contact of these proteins with the host mucosal surface after secretion.


Assuntos
Antígenos de Helmintos/isolamento & purificação , Echinostoma/imunologia , Equinostomíase/imunologia , Imunoglobulinas/química , Proteômica/métodos , Actinas/isolamento & purificação , Animais , Western Blotting , Eletroforese em Gel Bidimensional , Frutose-Bifosfato Aldolase/isolamento & purificação , Proteínas de Choque Térmico HSP70/isolamento & purificação , Imunoglobulinas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosfopiruvato Hidratase/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
20.
Gynecol Endocrinol ; 24(12): 691-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19172538

RESUMO

AIM: To evaluate with validated instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy (AHT). DESIGN: Randomised, double-blind, double-dummy study with two parallel treatment arms. PATIENTS AND METHODS: Forty-seven healthy post-menopausal women, aged 45-64 years, were evaluated using the Female Sexual Function Index (FSFI) and the menopause-specific quality of life questionnaire (MENQOL). Of them, 40 diagnosed with sexual dysfunction were randomised (1:1) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo. After 3 months follow-up, FSFI and MENQOL questionnaires were administered for a second time. RESULTS: Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor, psychological, physical and sexual symptoms. As expected, FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly. In addition, at the end of the study, 68.7% of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI (p < 0.0001). CONCLUSIONS: Adding methyl-testosterone to hormone therapy improves quality of life and sexuality in post-menopausal women with sexual dysfunction.


Assuntos
Terapia de Reposição Hormonal/métodos , Metiltestosterona/administração & dosagem , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Qualidade de Vida , Estatísticas não Paramétricas , Inquéritos e Questionários
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