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1.
Ann Oncol ; 30(3): 447-455, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30596880

RESUMEN

BACKGROUND: Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib. PATIENTS AND METHODS: Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented. RESULTS: Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, -52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months. CONCLUSION: Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy. CLINICAL TRIAL REGISTRATION: NCT02535507.


Asunto(s)
Acrilamidas/administración & dosificación , Aminoquinolinas/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Receptor ErbB-2/genética , Acrilamidas/efectos adversos , Adulto , Afatinib/administración & dosificación , Anciano , Anciano de 80 o más Años , Aminoquinolinas/efectos adversos , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Mutación/genética , Organoides/efectos de los fármacos , Organoides/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Receptor ErbB-2/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Support Care Cancer ; 27(12): 4649-4654, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30941579

RESUMEN

PURPOSE: While the incidence of sexual dysfunction after treatment for gynecologic malignancies is well documented, few studies describe how patients want healthcare providers to address these concerns. The objective of this study was to evaluate changes in sexual function and describe patient preferences regarding healthcare provider roles in addressing and treating sexual dysfunction in gynecologic cancer survivors. METHODS: Patients undergoing gynecologic cancer treatment from 2013 to 2014 at a single University-based Gynecologic Cancer clinic were surveyed using a modified Changes in Sexual Function Questionnaire (CSFQ), along with questions relating to healthcare provider interactions and preferences. RESULTS: Among 277 eligible patients approached to participate, 85 (30.7%) completed the survey. The mean age was 52.2 ± 12.3 years; most were non-Hispanic White (78.8%), partnered (73.2%), had endometrial or ovarian cancer (30.6% and 44.7%, respectively), and were in surveillance (57.3%). Most women (64.7%) reported much or great sexual enjoyment 1 year prior to cancer treatment which decreased to 27.4% currently; 33.3% report only rare sexual activity. There were no statistically significant differences in mean total CSFQ scores by treatment modality. A minority wanted healthcare providers to initiate sexual health discussions (25.3%); the remaining reported not wanting sexual health addressed or preferred raising the issue themselves. The most commonly cited barrier to communication was the feeling that there are more important issues to discuss with their oncology providers (46.2%). CONCLUSIONS: While gynecologic cancer patients report changes in sexual function following cancer therapy, many believe there are other issues more paramount to be addressed. Further studies are warranted to develop better strategies for addressing sexual health in women receiving treatment for gynecologic cancers.


Asunto(s)
Neoplasias de los Genitales Femeninos/terapia , Disfunciones Sexuales Fisiológicas/terapia , Supervivientes de Cáncer/psicología , Estudios Transversales , Femenino , Neoplasias de los Genitales Femeninos/fisiopatología , Neoplasias de los Genitales Femeninos/psicología , Humanos , Persona de Mediana Edad , Prioridad del Paciente , Calidad de Vida , Conducta Sexual/fisiología , Conducta Sexual/psicología , Disfunciones Sexuales Fisiológicas/fisiopatología , Disfunciones Sexuales Fisiológicas/psicología , Salud Sexual
3.
Br J Cancer ; 112(7): 1251-6, 2015 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-25742473

RESUMEN

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.


Asunto(s)
Disruptores Endocrinos/envenenamiento , Linfoma/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/estadística & datos numéricos , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Linfoma/inducido químicamente , Masculino , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Factores de Riesgo , Factores Sexuales
4.
Haemophilia ; 20(6): 771-6, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25039669

RESUMEN

The objective of this study was to evaluate the inhibitor development (ID) in previously untreated patients (PUPs) with severe haemophilia A (FVIII ≤ 0.01 IU mL(-1) ). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7 years. Eligible patients had at least 20 exposure days (ED) or had developed an inhibitor. The odds ratio (OR) and 95% confidence intervals (95% CI) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A PUPs were studied. Thirty-four (34%) developed an inhibitor (24/34 of high titre). Inhibitors developed in 25/63 (40%) patients with a high-risk mutation. ID was most frequent in Aboriginals (86%). Dose intensity (IU kg(-1)  day(-1) X number of ED) at first exposure to factor VIII (FVIII) was associated with a crude OR increase of 1.10 (95% CI: 0.99-1.23) with each increase of 100 dose-intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to FVIII concentrate were associated with a crude OR for ID of 7.63 (95% CI: 2.14-27.17) and 5.08 (95% CI: 1.11-23.31) respectively. ID according to FVIII concentrate used was: Advate (®) 18/50 (36%), Kogenate FS(®) or Helixate FS(®) 15/36 (42%), Wilate(®) 0/11 and Xyntha(®) 1/2. In multivariate analysis, Aboriginal ethnicity (OR = 11.69; 95% CI: 1.11-122.86) and haemarthrosis (OR = 4.49; 95% CI: 1.08-18.61) were statistically significant. The cumulative incidence of ID in severe haemophilia A PUPs was 34% and varied according to ethnicity, type of bleeding at first ED, type of FVIII product and dose intensity at first exposure.


Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/inmunología , Hemofilia A/epidemiología , Hemofilia A/inmunología , Inhibidores de Factor de Coagulación Sanguínea/sangre , Canadá/epidemiología , Preescolar , Factor VIII/genética , Factor VIII/uso terapéutico , Estudios de Seguimiento , Encuestas de Atención de la Salud , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Humanos , Incidencia , Lactante , Recién Nacido , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Masculino , Mutación , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
5.
Sci Total Environ ; 933: 172999, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38714261

RESUMEN

Unconventional hydrocarbon production has sparked public concerns for several years, especially regarding potential potable groundwater contamination by hydrocarbons, brines, and various chemicals related to hydraulic fracturing operations. One possible contamination mechanism is upward migration of deep-seated contaminants over large vertical distances, through preferential pathways such as leaky well casings or permeable geological faults. In New Brunswick (Canada), thermogenic hydrocarbons and brackish water were previously reported in shallow water wells, some of them located close to unconventional gas wells or to major faults, but the exact origin of these fluids remained uncertain. The objective of this paper is to determine whether the presence of these fluids is the result of migration from the deep (>1 km) hydrocarbon bearing units (via natural or anthropogenic migration pathways), or whether they rather originate within the shallow aquifer (<100 m) or from intermediate zone. Tracking fluid origin was achieved by fingerprinting compositional and isotopic values of three indicators: 1) water isotopic signature (including tritium (3H), radiocarbon (14CDIC), δ18OH2O, δ2HH2O), 2) salinity (including Na, Ca, K, SO4, Cl, Br, 87Sr/86Sr), and 3) hydrocarbons (compositional data and δ13CCH4). These various analyses were conducted, when relevant, on samples of different matrices composing the hydrogeological system, namely shallow groundwater (12-90 m depth), shallow bedrock gas (8-131 m), and intermediate zone evaporitic rocks (173-332 m); they were compared with previously published values for deep basin brines and gases (1940-3168 m) from the hydrocarbon bearing Carboniferous Albert Formation. This unique suite of indicators, analytes and matrices allowed drawing the conclusion that thermogenic gas and high salinities present in the sampled wells were naturally occurring and originating from shallow and intermediate-zone bedrock units. Results obtained through this approach did not provide any evidence that hydrocarbon wells in this area have acted as preferential migration pathways for deep-seated fluids towards shallow aquifers.

6.
Haemophilia ; 18(5): 805-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22500891

RESUMEN

Radiosynoviorthesis (RS) is an intra-articular injection of a radioactive colloid for the treatment of synovitis administered most often to patients with rheumatoid arthritis or haemophilia. Although highly cost-effective in comparison with surgical or arthroscopic synovectomy, the risk of cancer associated with this treatment is not well known. We evaluated the incidence of cancer in a group of patients treated with RS. A cohort of 2412 adult patients with a variety of underlying conditions (mainly rheumatoid arthritis) and treated with at least one RS between January 1976 and December 2001, was recruited from two centres in Montréal. Cancer incidence and mortality data for cohort members over that time period were obtained from regulatory agencies using linkage. Background rates for all and specific types of cancer were obtained for the provincial (Québec) and national (Canada) population according to age, gender and calendar period categories. Category-specific rates in the cohort were compared with rates in similar categories from the general population generating standardized incidence ratios (SIR). The effects of specific isotope doses and of number of RS treatments were analysed using a Cox-regression model. No increase in the risk of cancer was observed (SIR 0.96; 95% confidence interval 0.82-1.12). There was no dose-response relationship with the amount of radioisotope administered or number of RS treatments. The study provides some indication for the safety of the procedure but homogenous diagnostic groups of younger patients (such as haemophilic patients) receiving RS will need more evaluation.


Asunto(s)
Hemofilia A/radioterapia , Neoplasias/etiología , Radioisótopos/efectos adversos , Sinovitis/radioterapia , Adulto , Anciano , Artritis Reumatoide/complicaciones , Artritis Reumatoide/radioterapia , Estudios de Cohortes , Coloides , Femenino , Hemofilia A/complicaciones , Humanos , Incidencia , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Radioisótopos/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo , Sinovitis/etiología , Adulto Joven
7.
Plant Dis ; 96(7): 973-978, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30727209

RESUMEN

Bacterial wilt, caused by Ralstonia solanacearum, can result in severe losses to tomato (Solanum lycopersicum) growers in the southeastern United States, and grafting with resistant rootstocks may be an effective strategy for managing this disease. However, R. solanacearum populations maintain considerable diversity, and little information is known regarding the efficacy of commercially available rootstocks to reduce bacterial wilt incidence and subsequent crop loss in the United States. In this study, tomato plants grafted onto 'Dai Honmei' and 'RST-04-105-T' rootstocks had significantly lower area under the disease progress curve (AUDPC) values compared with nongrafted plants (P < 0.05). Across three locations in North Carolina, final bacterial wilt incidence for non- and self-grafted plants was 82 ± 14 to 100%. In contrast, bacterial wilt incidence for the grafted plants was 0 to 65 ± 21%. Final bacterial wilt incidence of plants grafted with Dai Honmei rootstock was 0 and 13 ± 3% at two locations in western North Carolina but 50 ± 3% at a third site in eastern North Carolina. Similarly, grafting onto RST-04-105-T rootstock significantly reduced AUDPC values at two of the three locations (P < 0.05) compared with that of the nongrafted plants, but performed poorly at the third site. Total fruit yields were significantly increased by grafting onto resistant rootstocks at all three sites (P < 0.05). Regression analyses indicated that yield was significantly negatively correlated with bacterial wilt AUDPC values (R2 was 0.4048 to 0.8034), and the use of resistant rootstocks enabled economically viable tomato production in soils naturally infested with R. solanacearum.

8.
Clin Lung Cancer ; 23(2): e90-e98, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34953676

RESUMEN

BACKGROUND: NaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumors including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts. METHODS: Analyses were performed on archival formalin fixed paraffin embedded primary tumor specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 - 300) were calculated for each core tissue sample (H-score = % tumor cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive. RESULTS: Of 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029). CONCLUSION: High NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIb/metabolismo , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica/métodos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico
9.
Clin Nephrol ; 76(4): 323-8, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21955868

RESUMEN

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure. In all FLD cases, a mutation has been found in the coding sequence of the LCAT gene. FLD is clinically distinguished from an acquired form of LCAT deficiency by the presence of corneal opacities. Here we describe a 36-year-old woman presenting with clinical, pathological, and laboratory data compatible with FLD. Her mother and elder sister had corneal opacities. However, genetic analysis revealed there were no mutations in the LCAT coding sequences and no alterations in LCAT mRNA expression. Furthermore, we were unable to find any underlying conditions that may lead to LCAT deficiency. The present case therefore demonstrates that LCAT deficiency may be caused by factors other than mutations in the coding sequence and we suggest that a translational or posttranslational mechanism may be involved.


Asunto(s)
Deficiencia de la Lecitina Colesterol Aciltransferasa/etiología , Adulto , Biopsia , Opacidad de la Córnea/etiología , Opacidad de la Córnea/genética , Femenino , Humanos , Deficiencia de la Lecitina Colesterol Aciltransferasa/diagnóstico , Deficiencia de la Lecitina Colesterol Aciltransferasa/genética , Mutación , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
10.
Eur Spine J ; 20(1): 123-8, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20700609

RESUMEN

In adolescent idiopathic scoliotic girls, postural imbalance is attributed to a sensory rearrangement of the motor system on the representation of the body in space. The objectives of this study were to test if the anteroposterior (AP), mediolateral (ML) and resultant body-head and trunk center of mass (COM) horizontal offsets were similar in able-bodied and scoliotic girls and if these offsets were related to the center of pressure displacements. A total of 21 adolescent idiopathic scoliosis girls and 20 able-bodied girls participated in this study. Their body COM position and that of the head and trunk were estimated according to Damavandi et al. (Med Eng Phys 31:1187-1194, 2009). The COP range and speed in both AP and ML axes were calculated from force plate measurements in quiet standing. The AP offset of the able-bodied group was anterior to the body COM by 11.0 ± 15.9 mm, while that of the scoliotic group was posterior to it by -17.3 ± 11.2 mm. The able-bodied group maintained their head-trunk segment COM more to the right by 14.1 ± 13.1 mm, while that of the scoliotic group was nearly over their body centerline. The scoliotic girls presented higher values for COP range and COP speed than the able-bodied girls. The resultant COM offset was correlated with both the ML COP range and speed only for the scoliotic girls. The small ML COM offset in the scoliotic girls was attributed to a compensatory action of the spinal deformity in the frontal plane resulting in a backward resultant COM offset to regain postural balance concomitant to an increase in the ML neuromuscular demand.


Asunto(s)
Equilibrio Postural/fisiología , Propiocepción/fisiología , Escoliosis/fisiopatología , Adolescente , Análisis de Varianza , Niño , Femenino , Humanos , Movimiento/fisiología
11.
J Investig Allergol Clin Immunol ; 20(4): 289-94, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20815306

RESUMEN

BACKGROUND: Peanut allergy is an important public health problem in western countries. However, the risk factors associated with this allergy remain uncertain. OBJECTIVE: To determine whether the consumption of peanuts during pregnancy and breastfeeding is a risk factor for peanut allergy in infants. METHODS: We enrolled 403 infants in a case-control study. The cases were infants aged 18 months or less with a diagnosis of peanut allergy based on a history of clinical reaction after exposure to peanuts and the presence of peanut-specific immunoglobulin E. Controls were age-matched infants with no known clinical history or signs of atopic disease. The mothers of the children filled out a detailed questionnaire about maternal diet during pregnancy and breastfeeding, the infant's diet, the presence of peanut products in the infant's environment, and family history of atopy. RESULTS: The mean (SD) age of cases was 1.23 (0.03) years. The groups were comparable in terms of the rate and duration of breastfeeding. However, the reported consumption of peanuts during pregnancy and breastfeeding was higher in the case group and associated with an increased risk of peanut allergy in offspring (odds ratio [OR], 4.22 [95% confidence interval [CI], 1.57-11.30 and OR, 2.28 [95% CI, 1.31-3.97] for pregnancy and breastfeeding, respectively). Overall, the infants with peanut allergy did not seem to be more exposed to peanut products in their environment than the controls. CONCLUSION: Early exposure to peanut allergens, whether in utero or through human breast milk, seems to increase the risk of developing peanut allergy.


Asunto(s)
Antígenos de Plantas/metabolismo , Lactancia Materna/epidemiología , Transfusión Fetomaterna/inmunología , Hipersensibilidad al Cacahuete/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Antígenos de Plantas/inmunología , Lactancia Materna/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Inmunización , Lactante , Recién Nacido , Masculino , Exposición Materna/efectos adversos , Hipersensibilidad al Cacahuete/diagnóstico , Hipersensibilidad al Cacahuete/inmunología , Hipersensibilidad al Cacahuete/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Fenómenos Fisiologicos de la Nutrición Prenatal/inmunología , Factores de Riesgo
12.
Plant Dis ; 94(8): 1015-1021, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30743481

RESUMEN

Southern blight (Sclerotium rolfsii) and root-knot nematodes (Meloidogyne spp.) cause severe damage to fresh-market tomato (Solanum lycopersicum) throughout the southeastern United States. Grafting is an emerging technology in U.S. tomato production, and growers require information regarding the resistance characteristics conferred by rootstocks. In this study, southern blight (SB) and root-knot nematodes (RKN) were effectively managed using interspecific hybrid rootstocks. During 2007 and 2008, field trials were carried out at two locations that had soils naturally infested with S. rolfsii. At the end of the growing seasons, the mean SB incidence of nongrafted plants was 27 and 79% at the two sites. SB incidence among plants grafted onto rootstock cultivars Big Power (one location only), Beaufort, and Maxifort ranged from 0 to 5%, and area under the disease progress curve (AUDPC) values were lower than for nongrafted and self-grafted controls (P < 0.01). At one location, soils were naturally infested with RKN, and all three rootstocks reduced RKN AUDPC and RKN soil populations at first harvest (P < 0.01). Big Power was particularly effective at reducing RKN galling and RKN soil populations at final fruit harvest (P < 0.01). Fruit yield was higher when resistant rootstocks were utilized (P < 0.05), and in our study grafting was effective at maintaining crop productivity in soils infested with S. rolfsii and M. incognita.

13.
Orthopade ; 38(2): 114-6, 118-21, 2009 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-19212754

RESUMEN

Spinal deformities, and particularly scoliosis, are the most frequent forms of orthopedic deformities in children and adolescents. About 1-6% of the population has scoliosis. This disorder leads to severe spinal deformities and predominantly affects adolescent girls.Although the multifactorial origin of adolescent idiopathic scoliosis (AIS) is broadly recognized, the genetic causes of AIS are still largely unknown. Our previous studies suggested a generalized dysfunction of melatonin transduction (the hormone that is primarily produced in the brain and epiphysis). In the meantime we have demonstrated that such a defect of signal transduction is caused by chemical alterations, which inactivate the function of the inhibitory G protein-coupled melatonin receptors. This discovery has led to the development of the first blood test to detect children without symptoms who are at risk of developing scoliosis. Since a single function (cellular reaction to melatonin) is determined, the unique advantage of this test is that it can be performed without knowledge of mutations in defective genes that could provoke the onset of AIS.


Asunto(s)
Análisis Químico de la Sangre/métodos , Tamizaje Masivo/métodos , Melatonina/sangre , Escoliosis/sangre , Escoliosis/diagnóstico , Biomarcadores/sangre , Predisposición Genética a la Enfermedad/genética , Humanos , Escoliosis/fisiopatología
14.
J Foot Ankle Surg ; 47(5): 409-18, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18725120

RESUMEN

UNLABELLED: There is a need for a user-friendly system that can provide quick and reliable assessment of foot disorders. The study described in this report was undertaken to determine the inter-rater and intra-rater reliability of a computer-aided, color-coded, video-based system developed for the assessment of foot alignment in patients with and without pes cavus deformity. Initially, 15 pedal angles were repetitively measured 7 times on 6 color-coded images of both feet, in 20 healthy adults. From the 7 repetitive measurements, the intra-class correlation was calculated and analysis of variance was used to estimate the minimum number of trials that would be necessary to identify a statistically significant difference in the measurements. To determine intra-rater reliability, 5 examiners evaluated a single set of data taken from 10 subjects. Additionally, data were obtained for 20 subjects with pes cavus deformity. The average intra-class correlation coefficient (ICC) for the anglular measurements for 2 to 7 trials was 0.98 +/- 0.06, while the intra-rater reliability was 0.90 +/- 0.14. No statistically significant differences were observed between right and left foot angles in able-bodied subjects; whereas, in the pes cavus group, 8 different angular measurements were observed to be statistically significantly different. The results of this investigation indicate that a computer-aided, color-coded, video-based system can be used to make reliable measurements of postural alignment in patients with and without pes cavus. LEVEL OF CLINICAL EVIDENCE: 5.


Asunto(s)
Deformidades del Pie/fisiopatología , Pie/fisiopatología , Procesamiento de Imagen Asistido por Computador/métodos , Grabación en Video , Adulto , Fenómenos Biomecánicos , Estudios de Casos y Controles , Color , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fotograbar , Postura/fisiología , Reproducibilidad de los Resultados , Programas Informáticos
15.
Stud Health Technol Inform ; 123: 415-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17108461

RESUMEN

This study is part of a larger project regarding the development of a Spine Surgery Simulator (S3), which has shown good results for posterior instrumentation surgeries. The aim was to develop a biomechanical model for the anterior instrumentation of the scoliotic spine. A biomechanical model using flexible mechanism was developed and surgical manoeuvres (instrumentation, rod installation and compression) were reproduced. Validation of the model was done by comparing the results for the instrumented part of the spine to the post-operative data (analytical Cobb angles in the frontal and sagittal planes, plane of maximum deformity, etc.). To date, surgeries of four patients operated by thoracotomy were reproduced. Preliminary results show that anterior instrumentation of the scoliotic spine can be adequately modelled using pre-operative geometric data and using mechanical properties from literature. Once validated with a larger sample of cases, the anterior instrumentation model could be implemented into S3 and used by orthopaedic surgeons to test various instrumentation strategies in virtual reality before performing the actual surgery.


Asunto(s)
Modelos Anatómicos , Escoliosis/cirugía , Adolescente , Fenómenos Biomecánicos , Simulación por Computador , Humanos , Quebec , Procedimientos Quirúrgicos Operativos
16.
Occup Environ Med ; 62(10): 688-94, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16169914

RESUMEN

BACKGROUND: The current prospective study investigated the hypothesis of metal fume fever (MFF) being a predictor for the development of respiratory symptoms and functional abnormalities. METHODS: The study consisted of a pre-exposure and two follow up assessments of 286 welding apprentices during an average period of 15 months. A respiratory and a systemic symptom questionnaire, skin prick tests to common allergens and metal salts, spirometry, and methacholine challenge tests were administered. RESULTS: Developing at least one positive skin prick test to a metallic salt solution was found in 11.8% of apprentices. Possible MFF (at least one of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, or shortness of breath) was reported by 39.2% of apprentices. The presence of at least one welding related respiratory symptom (cough, wheezing, or chest tightness) suggestive of welding related asthma was reported by 13.8%. MFF was significantly associated with these respiratory symptoms (OR = 4.92, 95% CI 2.10 to 11.52), after adjusting for age, atopy, smoking, physician diagnosed asthma, and symptoms of non-welding related asthma. Apprentices with possible MFF, and no welding related respiratory symptoms suggestive of welding related asthma at the first follow up, had an increased risk of developing the latter symptoms by the second follow up visit (OR = 7.4, 95% CI 1.97 to 27.45) compared with those not having MFF. MFF was not significantly associated with an increase in bronchial responsiveness. CONCLUSION: MFF could be a predictor for the development of respiratory symptoms but not for functional abnormalities in welders.


Asunto(s)
Enfermedades Pulmonares/etiología , Enfermedades Profesionales/etiología , Soldadura , Adulto , Contaminantes Atmosféricos/efectos adversos , Asma/etiología , Asma/inmunología , Bronquios/inmunología , Hiperreactividad Bronquial , Humanos , Exposición por Inhalación , Enfermedades Pulmonares/fisiopatología , Masculino , Metales/efectos adversos , Enfermedades Profesionales/fisiopatología , Oportunidad Relativa , Estudios Prospectivos , Pruebas Cutáneas
17.
Arch Intern Med ; 148(12): 2685, 1988 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2973775

RESUMEN

A 48-year-old man presented with the first symptoms of myasthenia gravis one month after a general anesthesia and a second dose of hepatitis B plasma vaccine. Whether either event may have acted as a nonspecific challenge to the patient's immune system is speculative, but the case is described to discover similar observations, if any.


Asunto(s)
Anestesia General/efectos adversos , Miastenia Gravis/etiología , Vacunas contra Hepatitis Viral/efectos adversos , Vacunas contra Hepatitis B , Virus de la Hepatitis B , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/terapia
18.
Ann Chir ; 130(4): 235-41, 2005 Apr.
Artículo en Francés | MEDLINE | ID: mdl-15847858

RESUMEN

The objective of this study was to evaluate the functionality of two intervertebral fusion implants, a porous nickel-titanium and a conventional titanium cage system in a sheep model. Eighteen sheep each received the two-implant devices at L2-L3 and L4-L5 lumbar levels. The sheep were sacrificed at three different postsurgical periods: three, six and 12 months. Lumbar segments were harvested. Qualitative (macroscopic and microscopic) and quantitative (histomorphometric) histological analysis were carried out on histological slides. The results indicated that a porous nickel-titanium had obtained a better osseointegration than the titanium implant. The functionality of two implants seemed to be influenced by the implant structure and shape. However, biocompatibility of two implants seemed comparable.


Asunto(s)
Vértebras Lumbares/cirugía , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Animales , Materiales Biocompatibles , Modelos Animales de Enfermedad , Ensayo de Materiales , Níquel , Porosidad , Ovinos , Titanio
19.
Pediatr Obes ; 10(3): 188-95, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24961681

RESUMEN

BACKGROUND: Fructose intake is associated with non-alcoholic fatty liver disease (NAFLD) development. OBJECTIVE: The objective of this study was to measure fructose absorption/metabolism in paediatric NAFLD compared with obese and lean controls. METHODS: Children with histologically proven NAFLD, and obese and lean controls received oral fructose (1 g kg(-1) ideal body weight). Serum glucose, insulin, uric acid, and fructose, urine uric acid, urine fructose, and breath hydrogen levels were measured at baseline and multiple points until 360 min after fructose ingestion. RESULTS: Nine NAFLD (89% Hispanic, mean age 14.3 years, mean body mass index [BMI] 35.3 kg m(-2)), six obese controls (67% Hispanic, mean age 12.7 years, mean BMI 31.0 kg m(-2)) and nine lean controls (44% Hispanic, mean age 14.3 years, mean BMI 19.4 kg m(-2)) were enrolled. Following fructose ingestion, NAFLD vs. lean controls had elevated serum glucose, insulin and uric acid (P < 0.05), higher urine uric acid (P = 0.001), but lower fructose excretion (P = 0.002) and lower breath hydrogen 180-min AUC (P = 0.04). NAFLD vs. obese controls had similar post-fructose serum glucose, insulin, urine uric acid and breath hydrogen, but elevated serum uric acid (P < 0.05) and lower urine fructose excretion (P = 0.02). CONCLUSIONS: Children with NAFLD absorb and metabolize fructose more effectively than lean subjects, associated with an exacerbated metabolic profile following fructose ingestion.


Asunto(s)
Fructosa/metabolismo , Hidrógeno/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Adolescente , Biomarcadores/metabolismo , Glucemia/metabolismo , Índice de Masa Corporal , Pruebas Respiratorias , Niño , Ingestión de Alimentos , Femenino , Humanos , Hidrógeno/química , Insulina/sangre , Resistencia a la Insulina , Masculino , Valor Predictivo de las Pruebas , Ácido Úrico/sangre
20.
J Nucl Med ; 31(4): 436-40, 1990 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2324819

RESUMEN

We examined the usefulness of technetium-99m-phytate (99mTc-phytate) hepatic scintigraphy in the evaluation of hepatic function, and the assessment of prognosis in patients with cirrhosis. Ninety-four patients with biopsy-documented cirrhosis had, at the time of entry into the study, a scintigraphy with 99mTc-phytate complexed with calcium in vivo. Extrahepatic uptake (EHU) of 99mTc-phytate on scintigraphy was graded from 0 (absent EHU) to 5 (important EHU) according to the relative distribution of the radiotracer between the liver, the spleen and the bone marrow. The severity of liver disease was also assessed according to the index of Child and Turcotte as modified by Pugh et al. Mean follow-up was 2 yr. EHU was correlated to the Pugh score (r = 0.73) and to survival. Survival at 2 yr was 97% for an EHU equal or inferior to 2.5, 62% for grades 3-4.5, and 31% for grade 5. In conclusion, hepatic imaging with 99mTc-phytate, in addition to its diagnostic value, also contains valuable prognostic information in patients with cirrhosis.


Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Compuestos de Organotecnecio , Ácido Fítico , Médula Ósea/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/mortalidad , Persona de Mediana Edad , Pronóstico , Curva ROC , Cintigrafía , Bazo/diagnóstico por imagen , Tasa de Supervivencia , Factores de Tiempo
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