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2.
Br J Cancer ; 109(11): 2941-50, 2013 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-24136148

RESUMEN

BACKGROUND: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. METHODS: 33 043 women (aged 25-65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. RESULTS: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4-89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0-67.5) of them. CONCLUSION: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.


Asunto(s)
Alphapapillomavirus/clasificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Adulto , Distribución por Edad , Anciano , Alphapapillomavirus/genética , Alphapapillomavirus/aislamiento & purificación , ADN Viral/análisis , Detección Precoz del Cáncer/métodos , Femenino , Finlandia/epidemiología , Genotipo , Humanos , Persona de Mediana Edad , Tipificación Molecular , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Prevalencia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Frotis Vaginal , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/etiología
3.
Reprod Domest Anim ; 47(2): e26-8, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21958004

RESUMEN

The case of a polyorchid Irish Setter is presented here. Castration and intra-abdominal testis removal were performed one year of age when one scrotal and one cryptorchid testis near the right inguinal canal were removed. Later it became apparent that there was still testosterone production. A third testis, abdominal cryptorchid, was found on the right side cranially and right to the bladder. The third testis had a strong cranial suspensory ligament and the tail of the epididymis was elongated. The ductus deferens did not enter the prostate but followed the gubernaculum to the inguinal canal near the stump of the previous operation on the caudal right testis. This suggests that two right cryptorchid testes had common ductus deferens.


Asunto(s)
Perros/anomalías , Orquiectomía/veterinaria , Enfermedades Testiculares/veterinaria , Testículo/anomalías , Animales , Hormona Liberadora de Gonadotropina/agonistas , Masculino , Enfermedades Testiculares/congénito , Enfermedades Testiculares/tratamiento farmacológico , Enfermedades Testiculares/cirugía
4.
Ann Oncol ; 22(9): 2007-2013, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21285132

RESUMEN

BACKGROUND: It is unknown how a very high tumor total HER2 (human epidermal growth factor receptor-2) content (H2T) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy. PATIENTS AND METHODS: H2T was measured using a novel quantitative assay (HERmark(®)) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial (ISRCTN76560285). In a chromogenic in situ hybridization (CISH) test, 197 (21.9%) patients had HER2-positive cancer and were randomly assigned to receive trastuzumab or control. RESULTS: Cancer H2T levels varied 1808-fold. High H2T levels were correlated with a positive HER2 status by CISH (P < 0.0001). A nonlinear association was present between H2T and the hazard of distant recurrence in a subpopulation treatment effect pattern plot analysis in CISH-positive disease. Patients with very high H2T (defined by ≥22-fold the median of HER2-negative cancers; 13% of CISH-positive cancers) did not benefit from adjuvant trastuzumab [hazard ratio (HR) 1.23; 95% confidence interval (CI) 0.33-4.62; P = 0.75], whereas the rest of the patients with HER2-positive disease by CISH (87%) did benefit (HR 0.52; 95% CI 0.28-1.00; P = 0.050). CONCLUSION: Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Receptor ErbB-2/biosíntesis , Adulto , Anciano , Neoplasias de la Mama/genética , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inmunohistoquímica , Hibridación in Situ , Persona de Mediana Edad , Receptor ErbB-2/genética , Taxoides/administración & dosificación , Trastuzumab , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina
5.
Int J Obes (Lond) ; 35(12): 1470-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21386806

RESUMEN

BACKGROUND: Viruses and bacteria like Chlamydia pneumoniae and Helicobacter pylori have been suggested to have a role in pathogenesis of overweight and obesity. OBJECTIVE: We studied whether C. pneumoniae-specific IgG antibodies are associated with elevated body mass index (BMI), waist and hip circumference, and/or waist-hip ratio (WHR), and whether the risk is more pronounced in the simultaneous presence of an ongoing inflammation as measured by elevated high-sensitive C-reactive protein (hsCRP) levels. SUBJECTS AND METHODS: Our study population was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), a general population sample of 12,058 live-born children. This cross-sectional study consisted of 5044 persons at 31 years of age. Serum C. pneumoniae IgG titers were measured by microimmunofluorescence test, and hsCRP levels by immunoenzymometric assay. RESULTS: C. pneumoniae IgG positivity (titer ≥ 32), both alone and jointly with elevated hsCRP (≥ 1.64 mg l(-1), an upper quartile), was found to significantly associate with elevated BMI in the whole study population and with elevated hip and waist circumference in women, yet no association with WHR was seen. The analyses were adjusted for sex (when appropriate), smoking, socioeconomic position, glucose, insulin, high- and low-density lipoprotein cholesterols, triglycerides, leukocytes and pulse pressure. CONCLUSION: These findings suggest that especially in women, persistent C. pneumoniae infection may be associated with overweight/obesity, independently of more traditional risk factors.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Infecciones por Chlamydophila/complicaciones , Chlamydophila pneumoniae/aislamiento & purificación , Obesidad/sangre , Obesidad/microbiología , Circunferencia de la Cintura , Relación Cintura-Cadera , Adulto , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/microbiología , Chlamydophila pneumoniae/inmunología , Estudios de Cohortes , Estudios Transversales , Femenino , Finlandia/epidemiología , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina G/sangre , Estilo de Vida , Masculino , Obesidad/epidemiología , Obesidad/patología , Medición de Riesgo , Muestreo , Encuestas y Cuestionarios
6.
Scand J Immunol ; 74(4): 383-9, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21645027

RESUMEN

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.


Asunto(s)
Síndrome Coronario Agudo/inmunología , Aggregatibacter actinomycetemcomitans/inmunología , Chaperonina 60/inmunología , Periodoncio/inmunología , Porphyromonas gingivalis/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Autoanticuerpos , Claritromicina/uso terapéutico , Reacciones Cruzadas , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Miocardio/inmunología , Periodontitis/inmunología , Reacción en Cadena de la Polimerasa , Saliva/microbiología
7.
Scand J Immunol ; 74(1): 95-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21352255

RESUMEN

A promoter polymorphism -174 G/C in the inflammatory cytokine interleukin-6 (IL-6) gene has been associated with differences in serum IL-6 levels and a risk for inflammatory conditions, such as cardiovascular diseases. We investigated whether this polymorphism is associated with Chlamydia pneumoniae, a common causative agent of respiratory infection with tendency for persistent infections, in 867 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible prolonged or chronic infection. The -174C allele was significantly associated with IgG seropositivity (P = 0.0002) and the persistence of IgG antibodies (P = 0.0002) as well as with slightly elevated C-reactive protein (CRP) levels (P = 0.003). In addition, the association was stronger when persistent C. pneumoniae antibodies were present together with elevated CRP than when either of them was positive alone (OR; 95% CI: 3.45; 2.00-5.98 and 1.41; 1.00-1.99, respectively). Our data suggest that IL-6 -174 G/C polymorphism is associated with persistence of C. pneumoniae antibodies and may be linked to the chronic or prolonged infection with systemic low-grade inflammation.


Asunto(s)
Anticuerpos Antibacterianos/genética , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Interleucina-6/genética , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Humanos , Masculino , Regiones Promotoras Genéticas , Adulto Joven
8.
Eur J Clin Microbiol Infect Dis ; 30(2): 233-41, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20938703

RESUMEN

The purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. This was an observational study. The primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae were studied as well as nasopharyngeal bacterial culture for the three former and urine pneumococcal antigen. Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapsed within two months than those with negative culture (odds ratio 7.3). In this study, half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.


Asunto(s)
Infecciones Bacterianas/microbiología , Portador Sano/microbiología , Nasofaringe/microbiología , Ruidos Respiratorios , Anticuerpos Antibacterianos/sangre , Bacterias/aislamiento & purificación , Infecciones Bacterianas/epidemiología , Portador Sano/epidemiología , Preescolar , Femenino , Hospitalización , Humanos , Lactante , Tiempo de Internación , Masculino , Recurrencia , Medición de Riesgo
9.
Ann Oncol ; 21(5): 968-73, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19819914

RESUMEN

BACKGROUND: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. PATIENTS AND METHODS: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. RESULTS: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63-1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). CONCLUSION: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundario , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Femenino , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento , Gemcitabina
10.
Scand J Immunol ; 72(2): 150-7, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20618774

RESUMEN

Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.


Asunto(s)
Aneurisma de la Aorta Abdominal/enzimología , Metaloproteinasa 8 de la Matriz/sangre , Enfermedades Vasculares Periféricas/enzimología , Peroxidasa/sangre , Factores de Edad , Anciano , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/inmunología , Femenino , Humanos , Modelos Lineales , Masculino , Metaloproteinasa 8 de la Matriz/inmunología , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/inmunología , Peroxidasa/inmunología , Curva ROC , Factores Sexuales , Inhibidor Tisular de Metaloproteinasa-1/sangre , Inhibidor Tisular de Metaloproteinasa-1/inmunología
11.
Epidemiol Infect ; 138(9): 1267-73, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20018131

RESUMEN

Chlamydia pneumoniae infection is said to be associated with obesity. We studied the association between C. pneumoniae infection and inflammation and increased BMI in 891 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible indication of chronic infection. Persistently high C-reactive protein (CRP) level (elevated on arrival and departure) (OR 2.2, 95% CI 1.3-3.9), and persistent C. pneumoniae antibodies (OR 2.1, 95% CI 1.5-2.8) were significant risk factors for overweight (BMI 25 kg/m2). In addition, those who had persistent antibodies and persistently elevated CRP levels, or those who had either of them, had a significantly higher BMI (kg/m2) compared to those who had neither of them (25.8 vs. 24.6 vs. 23.5, respectively; P<0.001). These results provide new information about the association between possible chronic C. pneumoniae infection and obesity in young men.


Asunto(s)
Infecciones por Chlamydophila/epidemiología , Infecciones por Chlamydophila/microbiología , Chlamydophila pneumoniae/aislamiento & purificación , Obesidad/epidemiología , Adolescente , Adulto , Asma/epidemiología , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Distribución de Chi-Cuadrado , Infecciones por Chlamydophila/sangre , Finlandia , Humanos , Inmunoglobulina G/sangre , Inflamación/sangre , Modelos Logísticos , Masculino , Factores de Riesgo , Fumar/epidemiología , Encuestas y Cuestionarios
12.
Scand J Immunol ; 70(1): 34-9, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19522765

RESUMEN

Chlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans. It can infect various cell types, e.g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. The susceptibility of macrophages from healthy individuals to C. pneumoniae infection is highly variable. In this study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC and CT genotypes was statistically significant (P = 0.032 and 0.022 respectively). The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes (P = 0.018). TLR2 Arg 753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth.


Asunto(s)
Chlamydophila pneumoniae/fisiología , Inmunidad Innata/genética , Macrófagos/microbiología , Polimorfismo Genético , Proteínas de Fase Aguda/genética , Proteínas Portadoras/genética , Infecciones por Chlamydia/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Técnicas In Vitro , Interleucina-6/genética , Receptores de Lipopolisacáridos/genética , Macrófagos/inmunología , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética
13.
Science ; 220(4603): 1279-81, 1983 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-6344216

RESUMEN

A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed. The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria.


Asunto(s)
Antígenos Bacterianos/inmunología , Chlamydia/inmunología , Enterobacteriaceae/inmunología , Lipopolisacáridos/inmunología , Chlamydia trachomatis/inmunología , Chlamydophila psittaci/inmunología , Escherichia coli/inmunología , Salmonella typhimurium/inmunología
14.
Eur J Neurol ; 16(12): 1305-11, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19570145

RESUMEN

BACKGROUND: We analysed data from three clinical trials in Parkinson's disease (PD) patients with wearing-off to determine whether early enhancement of levodopa therapy with entacapone can lead to better long-term outcomes than delayed entacapone treatment. METHODS: Post-hoc analysis of pooled data from three randomized, double-blind, placebo-controlled studies and their long-term, open-label extension phases. In all three studies, patients on levodopa/dopa-decarboxylase inhibitor (DDCI) were first randomized to entacapone ('early-start' group) or placebo ('delayed-start' group) for the initial 6-month double-blind phase, after which all patients received open-label levodopa/DDCI and entacapone treatment for up to 5 years. RESULTS: A total of 488 PD patients with wearing-off were included in the analysis. A statistically significant benefit of early initiation of levodopa/DDCI and entacapone was found, with an improvement in Unified Parkinson's Disease Rating Scale Part III (motor) score of -1.66 (95% confidence intervals [-3.01, -0.31]) points compared with the delayed-start treatment group (P < 0.05). Levodopa/DDCI and entacapone therapy was well tolerated. There was no excess of dyskinesia in the early-start group. CONCLUSIONS: These data suggest that early rather than delayed addition of entacapone to levodopa/DDCI in PD patients with wearing-off provides a modest clinical benefit over levodopa/DDCI that is maintained for up to 5 years.


Asunto(s)
Antiparkinsonianos/administración & dosificación , Catecoles/administración & dosificación , Nitrilos/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/efectos adversos , Catecoles/efectos adversos , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos
15.
Cerebrovasc Dis ; 27(6): 599-607, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19407443

RESUMEN

BACKGROUND: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. METHODS: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. RESULTS: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. CONCLUSIONS: Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.


Asunto(s)
Enfermedades de las Arterias Carótidas/epidemiología , Hipertensión Inducida en el Embarazo , Preeclampsia , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Estudios Transversales , Progresión de la Enfermedad , Femenino , Finlandia/epidemiología , Encuestas Epidemiológicas , Humanos , Modelos Logísticos , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , Ultrasonografía
16.
Eur J Cancer ; 115: 120-127, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31132742

RESUMEN

BACKGROUND: It is generally agreed to centralise treatment of childhood cancers (CCs). We analysed (1) the degree of centralisation of CCs in European countries and 2) the relations between centralisation and survival. PATIENTS AND METHODS: The analysis comprised 4415 CCs, diagnosed between 2000 and 2007 and followed up to the end of 2013, from Belgium, Bulgaria, Finland, Ireland, the Netherlands and Slovenia. All these countries had national population-based cancer registries and were able to provide information on diagnosis, treatment, treatment hospitals, and survival. Each case was then classified according to whether the patient was treated in a high- or a low-volume hospital among those providing CC treatment. A Cox proportional hazard model was used to calculate the relation between volume category and five-year survival, adjusting by age, sex and diagnostic group. RESULTS: The number of hospitals providing treatment for CCs ranged from six (Slovenia) to slightly more than 40 (the Netherlands and Belgium). We identified a single higher volume hospital in Ireland and in Slovenia, treating 80% and 97% of cases, respectively, and three to five major hospitals in the other countries, treating between 65% and 93% of cases. Outcome was significantly better when primary treatment was given in high-volume hospitals compared to low-volume hospitals for central nervous system tumours (relative risk [RR] = 0.71), haematologic tumours (RR = 0.74) and for all CC combined (RR = 0.83). CONCLUSION: Treatment centralisation is associated with survival benefits and should be further strengthened in these countries. New plans for centralisation should include ongoing evaluation.


Asunto(s)
Servicios Centralizados de Hospital/organización & administración , Hospitales de Alto Volumen , Hospitales de Bajo Volumen/organización & administración , Neoplasias/terapia , Servicio de Oncología en Hospital/organización & administración , Adolescente , Edad de Inicio , Niño , Preescolar , Europa (Continente)/epidemiología , Femenino , Disparidades en Atención de Salud/organización & administración , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias/mortalidad , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
17.
Scand J Immunol ; 67(3): 279-84, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18194359

RESUMEN

Chlamydia pneumoniae, an intracellular microbe, causes respiratory infections and may participate in the development of atherosclerosis. It is able to survive and multiply in macrophages. The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied. Intracellular growth of C. pneumoniae, as an indicator of susceptibility to infection, was compared to serum levels of C-reactive protein, soluble CD14 (sCD14), human heat shock protein (HSP)-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The production of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. Chlamydia pneumoniae production associated positively with serum C. pneumoniae IgA (titre: > or =10) and hHSP-IgG and negatively with sCD14 concentration. The association between sCD14 concentration, C. pneumoniae IgA and human HSP-IgG antibodies and C. pneumoniae production was statistically significant only among males. Age and gender did not correlate with the production. We hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Infecciones por Chlamydia/inmunología , Proteínas de Choque Térmico/inmunología , Receptores de Lipopolisacáridos/sangre , Macrófagos/microbiología , Monocitos/microbiología , Adulto , Infecciones por Chlamydia/sangre , Chlamydophila pneumoniae/inmunología , Susceptibilidad a Enfermedades/inmunología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
18.
Clin Microbiol Infect ; 14(3): 207-12, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18070131

RESUMEN

Chlamydia pneumoniae respiratory tract infections were studied in 512 male military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract infections requiring a medical consultation were analysed prospectively. At baseline, at end of service, and during each episode of respiratory infection, blood samples were obtained for measurement of C. pneumoniae antibodies. Data concerning the clinical features of each infection episode were collected. Serological evidence of acute C. pneumoniae infection was found in 34 of the 512 conscripts with antibody data available, including 9.8% of the asthmatic subjects and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory tract infections included 13 episodes of mild upper respiratory tract infection and seven episodes of sinusitis, with five episodes involving asthma exacerbation. Two of three pneumonias were primary infections. Primary infections were diagnosed in five subjects, and re-infection/reactivation in 19 subjects, with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects (p 0.180). Prolonged infections were present in six asthmatic subjects and one non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections, ranging from common cold to pneumonia, were associated with serologically confirmed C. pneumoniae infections. Infections were often mild, with common cold and sinusitis being the most common manifestations. Acute, rapidly resolved C. pneumoniae infections were equally common among asthmatic subjects and non-asthmatic subjects, whereas prolonged infections were more common among subjects with asthma.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Asma/complicaciones , Infecciones por Chlamydophila/epidemiología , Chlamydophila pneumoniae/aislamiento & purificación , Neumonía Bacteriana/epidemiología , Adulto , Infecciones por Chlamydophila/inmunología , Infecciones por Chlamydophila/microbiología , Infecciones por Chlamydophila/fisiopatología , Chlamydophila pneumoniae/inmunología , Finlandia/epidemiología , Humanos , Masculino , Personal Militar , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/fisiopatología , Prevalencia , Estudios Prospectivos , Infecciones del Sistema Respiratorio/microbiología , Sinusitis/microbiología
19.
Biochem Pharmacol ; 71(6): 735-41, 2006 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-16414027

RESUMEN

Chlamydial infections are very common worldwide. All chlamydial species have a tendency to cause persistent infections, which have been associated to several chronic diseases including blinding trachoma, infertility and coronary heart disease (CHD). At present, no efficient treatment for the eradication of chronic chlamydial infections exists and, thus, new antichlamydial compounds are urgently needed. This study was designed to screen antichlamydial activity of natural flavonoids and other natural and structurally similar synthetic compounds against Chlamydia pneumoniae in human cell line (HL). HL cells were infected with C. pneumoniae and incubated 72 h with studied compounds. Reduction in the number of inclusions was determined with immunofluorescence staining. In vitro minimum inhibitory concentration was also determined for some of the most active compounds. Thirty seven percentage of the studied compounds (57 in total) were highly active against C. pneumoniae and all the studied compounds were non-toxic to the host cells at studied concentrations. Our study revealed direct antichlamydial effect for selected polyphenolic compounds against C. pneumoniae, in vitro. We also demonstrated the ability of some of the investigated compounds to accumulate inside cells or into cell membranes and cause inhibition, even when present only prior to infection.


Asunto(s)
Antibacterianos/farmacología , Chlamydophila pneumoniae/efectos de los fármacos , Flavonoides/farmacología , Fenoles/farmacología , Antibacterianos/química , Antibacterianos/clasificación , Línea Celular , Chlamydophila pneumoniae/crecimiento & desarrollo , Dieta , Flavonoides/química , Flavonoides/clasificación , Humanos , Pruebas de Sensibilidad Microbiana , Fenoles/química , Fenoles/clasificación , Polifenoles , Relación Estructura-Actividad Cuantitativa
20.
Clin Microbiol Infect ; 12(2): 118-22, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16441448

RESUMEN

The prevalence and persistence of antibodies against cytomegalovirus (CMV), herpes simplex virus types 1 (HSV1) and 2 (HSV2), Helicobacter pylori and Chlamydia pneumoniae were determined in Alaskan Eskimos. The study included 610 individuals (mean age 43 +/- 15 years; 45% males) participating in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Archived serum samples and those collected during the GOCADAN study were analysed for antibodies against the above pathogens by ELISA. The current prevalence of antibody seropositivity was 94% to CMV, 90% to HSV1, 38% to HSV2, 80% to H. pylori, and 42% to C. pneumoniae. The persistence of antibodies (in both archived and current samples) against CMV, HSV1 and H. pylori was high (83%, 84% and 67%, respectively) compared with those against HSV2 (26%) and C. pneumoniae (29%). Moreover, the seroconversion rates to these organisms were low. Most individuals acquired CMV, HSV1 and H. pylori antibodies by the age of 24 years (94%, 90% and 72%, respectively), and >50% carried HSV2 and C. pneumoniae antibodies by the age of 45 years. There were gender differences in antibody seropositivity rates. Over 70% of individuals had antibodies to at least three of the five pathogens tested. The study demonstrated the high prevalence and lifelong persistence of multiple antibodies, suggesting chronic infections among Alaskan Eskimos.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Infecciones por Chlamydophila/epidemiología , Infecciones por Helicobacter/epidemiología , Infecciones por Herpesviridae/epidemiología , Inuk , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Alaska/epidemiología , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Citomegalovirus/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Infecciones por Herpesviridae/inmunología , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Factores Sexuales
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