Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

UNLABELLED: The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients. INTRODUCTION: The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients. METHODS: Fifty consecutive Caucasian patients, aged 30-50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects' calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed. RESULTS: Patients showed reduced BMD (Z-scores LS -0.45 ± 1.00, FN -0.56 ± 1.01, FT -0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency. CONCLUSIONS: EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

Hemostatic abnormalities in patients with Ehlers-Danlos syndrome.

Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.

PURPOSE: Transradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions. METHODS AND MATERIALS: Patients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications. RESULTS: From July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6% with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9%) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1%) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups. CONCLUSIONS: Transradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

Sensory receptor sensitivity in autistic children: response times to proximal and distal stimulation.

On the basis of behavioral observation, it has been postulated that autistic children prefer proximal (touch, taste) to distal (sight, hearing) sensory modalities. To assess this systematically, autistic children's simple response times were measured with auditory, visual, and tactile stimulation. Children were studied for up to 25 sessions of 40 trials with each modality. Response times were significantly related to mental age. Autistic children's responses were significantly slower than normal children's. However, autistic children and normal children had the same pattern, fastest responding to auditory stimuli and slowest responding to tactile stimulation. Autistic children's preference for proximal stimuli probably reflects a continuation of immature behavior rather than a basic disturbance in sensory receptor sensitivity.

[DNA methylation analysis in environmental and occupational cancer research]. / Studio della metilazione del DNA nella valutazione della cancerogenicità di agenti ambientali e occupazionali.

The present paper reviews recent laboratory methods and experimental evidence concerning epigenetic biomarkers involved in carcinogenesis mechanisms. We introduce DNA methylation and its role in gene expression control. DNA methylation analysis may allow to identify early changes leading to cancer and other chronic diseases. We describe here strategies for laboratory analyses and their possible applications. We examine results from recent experimental studies suggesting that the effects of certain occupational agents are mediated by alterations in DNA methylation. Planning and conducting investigations on exposed human subjects will allow to verify whether DNA methylation changes identified in animal and in-vitro studies may be used as early-effect and susceptibility biomarkers. DNA methylation analysis has the potential for future applications in risk assessment and prevention programs conducted on subjects exposed to human carcinogens.

[Cervical cancer prevention: an update]. / Prevención del cáncer de cérvix: puesta al día.

It has been seen an increase of the cervical cancer and of intraepithelial cancer in the last years. The most important risk factors for cervical cancer are sexual conduct, early of sexual relationships, number of partners, cigarettes, oral anticonceptive, pregnancy, immunosuppression, sexually transmitted illness. And an important role of the Human Papilloma Virus. The HPV has been classified in 3 groups; low risk, the most frequents are 11 and 6, middle risk, tipe 31, 33 and 35, and high risk, 16 and 18, that have frequent association with cervical cancer and with high grade intraepithelial lesions. The cervicovaginal citology is still the most accurate diagnosis method to detect SIL or CIN and invasive cancer in early stages, it is discussed the periodicity and group of women to whom the method must point. There are different options depending if it is a SIL of low or high grade or and cancer. With the possibility of doing follow up or treatment, such as. LLETZ, Laser, Criotraphy, cone and interferon for the preneoplastic lesions. The achievement of a vaccine for HPV could have a significant impact on these pathology.

Modulation of response to environmental stimulation in autistic children.

Autistic children's blood pressure, heart rate, peripheral blood flow (PBF), and peripheral vascular resistance (PVR) were measured during three types of tasks (reaction time, social interaction, at rest). The most highly functioning autistic children who learned the reaction time task to a criterion level had PBF measurements consistent with sensory intake during task performance and social interaction. The lower functioning children who failed to learn the task, even after 25 training sessions, showed PBF patterns consistent with rejection of external sensory information. When transferred from school to laboratory, the more impaired children showed greater response disruption and an increased heart rate, consistent with their behavioral need to preserve sameness. Autistic children appear to be more sensitive to the environment and may use behavioral strategies, such as avoiding environmental change and social interaction, as methods of reducing further disorganizing experiences. Disturbances in filtering environmental stimulation and modulating response to novelty may be part of the basic pathology of autism apparent during the 1st year of life.

Effects of inhalable particulate matter on blood coagulation.

BACKGROUND: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM-related hypercoagulability are still largely unknown. OBJECTIVES: To identify coagulation mechanisms activated by PM in a population with well-characterized exposure. METHODS: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue-type plasminogen activator (t-PA) antigen, D-dimer and C-reactive protein (CRP) in 37 workers in a steel production plant with well-characterized exposure to PM with aerodynamic diameter of < 1 mum (PM(1)) and coarse PM (PM(10) - PM(1)). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4-day work week. We analyzed differences between baseline and postexposure levels using a paired Student's t-test. We fitted multivariate mixed-regression models to estimate the associations of interquartile range PM(1) and coarse PM exposure with parameter levels. RESULTS: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (beta[PM(1)] = -0.33 s, P = 0.08; beta[PM(coarse)] = - 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (beta[PM(1)] = + 99 nm min, P = 0.02; beta[PM(coarse)] = + 66 nm min, P = 0.05), t-PA (beta[PM(1)] = + 0.72 ng mL(-1), P = 0.01; beta[PM(coarse)] = + 0.88 ng mL(-1), P = 0.04), and CRP (beta[PM(1)] = + 0.59 mg L(-1), P = 0.03; beta[PM(coarse)] = + 0.48 mg L(-1), P = 0.01). CONCLUSIONS: PM exposure did not show any short-term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long-term effects on inflammation and coagulation.

A pleiotropic Arabidopsis thaliana mutant with inverted root chirality.

Circumnutation is an oscillating movement of a growing plant organ that is believed to result from an endogenous rhythmic process intrinsic to growth. Circumnutating organs, as they extend, describe a helical trace. In Arabidopsis thaliana (L.) Heynh. circumnutation is particularly evident in primary roots and occurs, as in most plants, in a right-handed direction when viewed from above in the direction of the growing tips. We have discovered a pleiotropic mutant of Arabidopsis with left-handed root circumnutation. Major abnormalities of the mutant are: (i) a reduced size of all organs, mainly due to a defect in cell elongation or expansion; (ii) a zigzagging pattern of stem pith cells, reminiscent of the "erectoides" phenotype of the lk mutant of Pisum; (iii) roots of the mutant are gravitropic but as they grow, they form tight, left-handed coils. Genetically, the mutant depends on the presence of two independent monogenic recessive factors acting additively. The mutant alleles of both factors alter the growth of the aerial organs in a similar manner but differ at the root level: one mainly produces non-circumnutating roots, the other changes the direction of circumnutation from right to left hand.

XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk.

We recently reported an association between low DNA repair capacity, measured through the host-cell reactivation assay, and melanoma risk in subjects with dysplastic naevi or low tanning ability. We investigated the genetic basis for these findings by analysing the Asp312Asn and Lys751Gln polymorphisms of the XPD (ERCC2) DNA repair gene in the same subjects. Similar to our previous report, no significant association between XPD polymorphisms and melanoma risk was found in 176 melanoma cases and 177 controls (odds ratio (OR)=1.5, 95% confidence interval (CI)=0.9-2.5 for 312Asn; OR=1.3, 95% CI=0.8-2.1 for 751Gln, adjusted for age, gender, dysplastic naevi and pigmentation characteristics). However, XPD variants were associated with increased risk in older (>50 years) subjects (OR=3.4, 95% CI=1.6-7.3 for 312Asn; OR=2.3, 95% CI=1.1-4.9 for 751Gln). The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic naevi (OR=2.6, 95% CI=1.1-6.4). Subjects with low tanning ability and XPD variants exhibited a nonsignificant increase of melanoma risk (OR=2.3, 95% CI=0.7-7.0 for 312Asn; OR=3.0, 95% CI=1.0-8.8 for 751Gln). DNA repair capacity was slightly decreased in subjects carrying 751Gln alleles. XPD variants may modify melanoma risk in subjects with specific host characteristics, such as older age, lack of dysplastic naevi or low tanning ability.

Prevención del cáncer de cerviz: puesta al día / Cervical cancer prevention: a current status of the knowledge

Se ha observado en los últimos años un incremento del carcinoma del cuello uterino de neoplasia intraepitelial cervical,. Los factores de riesgo más importantes para el cáncer de cerviz son el inicio precoz, de las relaciones sexuales, el número de parejas sexuales, el tabaco, los anticonceptivos orales, paridad, estados de inmunosu-presión, y enfermedades de transmisión sexual. Igual-mente, se ha demostrado el importante papel del virus del papiloma humano. Se han clasificado en tres grupos de VPH: de bajo riesgo, tipos 6 y 11; de mediano riesgo, tipos 31, 33 Y 35 Y de alto riesgo, los mas frecuentemente encontrados son tipos 16 y 18, que presentan frecuente asociación con el cáncer del cuello uterino y con las lesiones intraepiteliales de alto grado. La citología cervicovaginal sigue siendo el método diagnóstico de mayor valor para detectar la neoplasia intracervical cervical(CIN) o lesiones escamosas (SIL) y el carcinoma invasivo estadios precoces, discutiéndose la periodicidad y el grupo de mujeres al cual debe apuntar este método. Existen diferentes conductas de acuerdo a si se trata de SIL de bajo o alto grado o carcinoma invasor. Con la posibilidad de realizar controlo tratamiento; como, vaporización con láser, asa diatérmica (LLETZ), crioterapia, conización y actualmente en estudio tratamiento médico con los retinoides, el 5-fluoro-uracilo e interferones para el tratamiento de las lesiones preneoplasicas. La creación de una vacuna contra el HPV podría tener un significativo impacto sobre esta patología.

It has been seen an increase of the cervical cancer and of intraephitlial cancer in the last years. The most important risk factors for cervix cancer are sexual conduct, early of sexual relationships. number of partners, cigarettes, oral anticonceptive, pregnancy, Inmunosupresion, sexually transmitted illness. And an important role of the Human Papiloma Virus. The HPV has been classified in 3 groups; low risk, the most frequents are II and 6, middle risk, type 31. 33 and 35. and high risk, 16 and 18, that have frequent association with cervical cancer and with high grade 'intraephitlial lesions. The cervicovaginal cytology is still the most accurate diagnosis method to detect SIL or CIN and invasive cancer in early stages, it is discussed the periodicity and group of women to whom the method must point. There are different options depending if it is a SIL of low or high grade or and cancer. With the possibility of doing follow up or treatment, such as. LLETZ, Laser, Criotraphy, cone and interferon for the preneoplastic lessons. The achievement of a vaccine for HPV could have a significant impact on this pathology.