EUROPLAN: a project to support the development of national plans on rare diseases in Europe.

BACKGROUND/AIMS: National Plans for Rare Diseases (RDs) are the common denominator of current public health policy concerns on RDs across the EU. With the aim of a better distribution of the available resources, they conjugate the European objective that aims at ensuring that patients with RDs have access to high-quality care - including diagnostics, treatment and rehabilitation - with the national priorities of selecting specific measures for adoption and implementation. METHODS: The European Project for Rare Diseases National Plans Development (EUROPLAN, www.europlanproject.eu) is cofunded by the EU Commission (DG-SANCO) and is coordinated by the Italian National Center for Rare Diseases of the Istituto Superiore di Sanità (ISS). The EUROPLAN goal is to promote the implementation of National Plans or Strategies to tackle RDs and share relevant experiences within countries, linking national efforts, through a common strategy at a European level. In order to fulfill these objectives, EUROPLAN involved health authorities, clinicians, scientists, the European Organisation for Rare Diseases (EURORDIS), and many other patient groups as associated and collaborating partners from several European countries. RESULTS: The project was launched in 2008 and foresaw 2 implementation phases: phase 1 (2008-2011) to build the consensus definition of operational tools (recommendations and indicators), and the ongoing phase 2 (2012-2015), mainly aimed at capacity building with the proactive involvement of multilevel stakeholders. EUROPLAN is facilitating and accelerating the implementation of National Plans in almost all EU and several non-EU Countries. CONCLUSIONS: EUROPLAN is a European and an international process more than a project, and it could be defined as a 'litmus test' demonstrating how the collaboration between institutions and patients' associations can accelerate the process of awareness and development of policies and actions.

Public health research on rare diseases.

Despite the low prevalence of Rare Diseases (RD), over 30 million EU citizens suffer from these conditions. This paper summarizes some aspects of these life-threatening chronic and debilitating diseases that usually require long term specialist care and costly formal and informal surveillance. Epidemiology does have an important role to play in the field of RD, since it provides appropriate methods and tools for assessing exposures and health outcomes. In this regard, the utility of registries, biobanks and population-based surveillance systems are discussed. The lack of effective diagnoses and treatments in RD patients often underlies their shortened life expectancy and quality of life. Due to the limited number of patients and the scarcity of relevant knowledge and expertise, coordination at European level is probably the best way of pooling the very limited resources available and provides a very high added-value. RD require the combined efforts of health and social care professionals, politicians, managers and researchers to increase the availability of effective disease management tools to improve care and to extend both life expectancy and Health Related Quality of Life.

[Renal cell carcinoma presenting as paraneoplastic neurological dysfunction]. / Carcinoma renal que debuta como cuadro neurológico paraneoplásico.

INTRODUCTION: Malignant tumors sometimes initiate as paraneoplastic syndromes even years before the most common symptoms appear. These first manifestations could be the key for the diagnosis of "occult" malignancy. METHODS: We report the case of a 66 year old man with a renal cell carcinoma. The first symptom was a paraneoplastic cerebellar degeneration appeared 6 years before the first urologic manifestations. CONCLUSIONS: A progressive cerebellar syndrome could be the first manifestation of a renal cell carcinoma, even years before the first urologic symptoms. We must suspect an occult neoplasia in such patients.

Multiple sclerosis in Gypsies from southern Spain: prevalence, mitochondrial DNA haplogroups and HLA class II association.

Occasional reports have mentioned the prevalence of multiple sclerosis (MS) among Gypsies, and no studies have examined to date the prevalence of MS or human leukocyte antigen (HLA) genetics associations in the Spanish Gypsy population. We decided to study the prevalence, mitochondrial DNA (mtDNA) haplogroups and HLA class II distribution among gypsies with MS in southern Spain. We searched for Gypsy MS patients and studied HLA class II alleles by polymerase chain reaction with sequence-specific oligonucleotide (PCR/SSO) probe hybridization or sequence-specific primers amplification. An additional study of the mtDNA haplogroups by sequencing of the hypervariable segments of the control region was also performed to provide details of their ethnic origin. Estimated prevalence of MS in the Gypsy population in Malaga was 52/100,000. No significant differences were found in mtDNA between Gypsy MS patients and Gypsy controls. DRB1*1501, DQB1*0602 and DQB1*0608 alleles were the only positive HLA association with MS. The Gypsies in our series have the same anthropological origin as other European gypsy groups, as shown by mtDNA haplogroups. Although interpreted with great caution because of the small sample size, we found that the prevalence of MS in Gypsies in Malaga is not as low as that in Central Europe, although it is significantly less than that found in Caucasians from Spain (75-79/100,000). DQB1*0602 was the strongest positive association found with Gypsy MS patients, and DRB1*1501-DQB1*0602 was the most frequent haplotype in this group.

Síndrome paraneoplásico cerebeloso asociado con carcinoma de ovario / Paraneoplastic syndrome with cerebellar degeneration associated with ovarian carcinoma

Presentamos el caso de una paciente afectada de un síndrome paraneoplásico con degeneración cerebelosa, como primera manifestación de un tumor ovárico en la que todos los estudios resultaron normales, a excepción de la presencia de un autoanticuerpo anti-Yo, que reconoce antígenos citoplasmáticos de las células de Purkinje del cerebelo. La sospecha de un tumor ovárico fue confirmada microscópicamente tras la extirpación de los dos anejos. (AU)

Functional characterization of colloidal phosphorus species in the soil solution of sandy soils.

The impact of mobile colloids on the transport of phosphorus in the subsurface environment is not well understood. We hypothesized that interactions between metals, organic matter, and P control the dynamics of mobile colloidal P species in excessively fertilized sandy soils. The effect of UV irradiation and additions of 32P, orthophosphate, Fe, Al, and NaF on the concentration of colloidal P was examined using gel filtration chromatography. In addition, molybdate unreactive P (MUP) was characterized using phosphomonoesterase assays. The high molecular mass reactive P (HMMRP) fraction did not react to orthophosphate additions, increased upon Al and Fe additions and decreased upon NaF addition and UV irradiation. These results support the hypothesis that HMMRP is present as organic matter-metal-orthophosphate complexes. The concentration of high molecular mass unreactive P (HMMUP) decreased upon UV irradiation. The MUP concentration slightly decreased upon incubation with phytase and acid phosphatase. These observations fitted well to the "protection" hypothesis, where hydrolyzable P bonds are protected from monoesterase attack through occlusion in colloidal material. Taken together, this study indicates the high potential for subsurface P loss by colloidal particles in soils excessively fertilized with animal manure.

Screening for atrial fibrillation in the community: a multicenter validation trial.

BACKGROUND: Atrial fibrillation (AF) is an important public health problem. This arrhythmia is common and associated with a high risk of stroke. Further, appropriate interventions in AF can reduce the risk of stroke by approximately 68%. Population studies show that a large group of patients have intermittent or chronic AF that remains unrecognized. If a simple screening test for this arrhythmia could be developed and validated, application of the technique across populations might identify AF patients for early treatment, potentially reducing the incidence of stroke. In this study, we sought to determine whether individuals taken from the general community could be taught to find and classify the pulse of another as very irregular, implying AF, or regular, implying normal sinus rhythm (NSR). The aim was to establish that pulse examination for potential AF could be performed by individuals with sufficient sensitivity and specificity to be effectively used as a screening procedure for this medically important arrhythmia. METHODS: We enrolled 178 subjects selected from the general community from four centers. Subjects received standardized education on the medical importance of AF and its signature, a very irregular pulse. A technique for palpating and characterizing the rhythm of the radial pulse was also taught. Without further coaching, subjects were then asked to find their pulse and then to find and classify the pulse of two models randomly presented who may or may not have had AF. RESULTS: Of the 178 subjects tested, 92% were able to find their own pulse; 17 (9.6%) were unable to find the pulse of one or both patient models and were, therefore, excluded from the study. Of the remaining 161 subjects, 76% (122 of 161) correctly identified the pulse in an AF model, and 86% (139 of 161) correctly identified the pulse in an NSR model. Results did not statistically differ as a function of age, educational status, or location. DISCUSSION: This multicenter trial established that given minimal standardized instructions, subjects from the general community can reliably and consistently find both their pulse as well as the pulse of another and to differentiate a regular pulse from a very irregular pulse. If similar educational programs were widely applied across large populations, periodic screening for AF might lead to earlier diagnosis and appropriate treatment for patients who have this major risk factor for stroke. These screening programs should be focused on the population over the age of 55 where the risk of stroke in AF increases with each decade.

Thromboembolism prophylaxis in chronic atrial fibrillation. Practice patterns in community and tertiary-care hospitals.

BACKGROUND AND PURPOSE: By 1992, several prospective trials established the efficacy of anticoagulation (AC) and to some extent antiplatelet (AP) agents in the prevention of stroke in the setting of atrial fibrillation (AF). The objective of this study was to determine whether practice patterns in AF stroke prophylaxis reflect the findings of clinical trials and whether stroke prophylaxis in AF differs between community hospitals and tertiary teaching hospitals. METHODS: Retrospectively, 1250 hospital charts were reviewed. After patients who had undergone recent surgery, received treatment for malignancy, or were not in chronic AF on discharge were eliminated, 651 remaining records were analyzed for the presence of 26 clinical factors influencing the selection of thromboembolism prophylaxis. Descriptive statistics and logistic regression were used to analyze the association between clinical and demographic factors and the decision to treat with AC, AP, or no specific antiembolic therapy. RESULTS: Of the 651 patients in AF, 273 (42%) received noemboli prophylaxis while 219 (34%) were treated with AC (warfarin), 146 (22%) were treated with AP, and 13 (2%) received both agents. Patients discharged in AF from community hospitals were significantly less likely to be treated with either AC or AP agents than patients discharged from tertiary centers. A strong bias against thromboembolism prophylaxis with either AC or AP agents in AF existed with age over 45 years. Multivariate logistic regression indicated that the decision to treat was associated only with the presence of prosthetic valve, history of prior stroke, mitral disease, and absence of a recent gastrointestinal bleed or occult blood in stool. Even after adjustment for these factors, a significant bias against treatment with either AC or AP agents with advancing age and discharge from community hospitals remained. CONCLUSIONS: Thromboembolism prophylaxis with either AC or AP agents is underutilized in the setting of AF. Furthermore, factors known to increase the risk of embolization in AF such as age, hypertension, diabetes, and heart disease were not associated with decisions to treat with either AP or AC agents. This study suggests that the use of clinical guidelines suggested by trials of thromboembolism prophylaxis in AF could reduce the incidence of stroke.

Molecular analysis and developmental expression of the focal adhesion kinase pp125FAK in Xenopus laevis.

Integrin-mediated cellular adhesion to components of the extracellular matrix (ECM) is important in a number of morphogenetic events that occur during vertebrate embryogenesis. Recent studies suggest that the focal adhesion kinase pp125FAK is involved in the regulation of integrin-dependent signaling processes triggered by cell adhesion to the ECM. We report the cDNA cloning and sequence analysis of the Xenopus homolog of pp125FAK. We also describe temporal and spatial patterns of FAK expression during early development. Xenopus FAK shares greater than 90% identity with its avian and mammalian homologs. FAK mRNA and protein are present in the fertilized egg and in cleavage stage embryos. During gastrulation, FAK protein expression increases significantly and is detected in mesoderm, marginal zone ectoderm, and cells of the blastocoel roof. Later in development, FAK is prominently expressed at intersomitic junctions, in the brain, and in several cranial nerves. Phosphotyrosyl-FAK is first detected during gastrulation, suggesting that the phosphorylation of FAK on tyrosine is developmentally regulated. These data indicate that FAK is likely to participate in a variety of integrin-ECM-dependent signaling events during morphogenesis.

Integrin expression in early amphibian embryos: cDNA cloning and characterization of Xenopus beta 1, beta 2, beta 3, and beta 6 subunits.

During embryogenesis cells modulate their adhesion to other cells and the surrounding extracellular matrix, in part, through the combination of integrins they express. In order to identify integrins that may mediate morphogenetic cell movements in the early Xenopus embryo, we have used polymerase chain reaction methods to isolate cDNAs encoding Xenopus integrin beta subunits. Based on deduced amino acid sequence, they are identified as homologs of human integrins beta 1, beta 2, beta 3 and beta 6. We also report the cloning and sequencing of cDNAs covering the complete coding region of Xenopus beta 3. Embryonic patterns of expression for these integrin beta subunit mRNAs have been examined both by RNase protection analysis and by whole mount in situ hybridization. In the early embryo the beta 1 subunit is encoded by a maternally transcribed mRNA expressed in all cells, but is most abundant in ectoderm and mesoderm. In contrast, Xenopus beta 3 mRNA is detected in the epidermis, bottle cells of the neural groove, and a subset of cells arising from the ventral blood islands. The beta 2 and beta 6 mRNAs are expressed at high levels in late tailbud stages, although very low levels of beta 6 are also detected in eggs and early embryos. These data provide evidence that multiple integrins are expressed at the earliest stages of vertebrate development coincident with the onset of morphogenesis.

Multiple sclerosis: a literature review.

The pathology of multiple sclerosis (MS) was first described over 150 years ago. An estimated 250,000 to 350,000 people are affected with MS in this country. Young adults between the ages of 20 and 50 years are most commonly affected, with the majority of patients experiencing a relapsing course and progressive functional disability. To date, researchers have been unable to discover a precipitating cause. However, many now believe MS develops due to exposure to some unknown virus in a genetically predisposed individual. The incidence of disease is limited in temperate climates and higher in northern latitudes. Neuroscience nurses frequently care for individuals with MS and must, therefore, maintain a familiarity with the current literature and research.

High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD.

We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy. Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA. Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices. This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage. Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS. Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy. Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.

Functional assessment scales: a study of persons with multiple sclerosis.

The purpose of this study was to investigate disability in persons with multiple sclerosis (MS) by using combinations of functional assessment scales and subscales to predict (1) the burden of care measured in minutes of assistance provided per day by another person in the home, and (2) the subject's level of satisfaction with life in general. The Functional Independence Measure (FIM), Incapacity Status Scale, Environmental Status Scale, and the Barthel Index had high intercorrelations with each other. Although each was predictive of the MS subject's physical care needs, the FIM was the most useful. A change in total FIM score of one point was equivalent to an average of 3.38 minutes of help from another person per day. With the Brief Symptom Inventory and the Environmental Status Scale, the FIM contributed to predicting the patient's general satisfaction as well. We propose that burden of care and subjective satisfaction with life be the standards by which functional assessment instruments are compared to reflect, in pragmatic terms, the impact of disability on the lives of individuals and on the human and economic resources of the community.

Alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase and creatine kinase in bronchial aspirate from neoplastic and normal pulmonary tissue.

The activities of 4 enzymes, i.e. alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase and creatine kinase were studied in bronchial aspirates and serums from two groups of subjects, the first one was composed of 14 subjects without active bronchopulmonary pathology and the other of 20 patients with lung cancer. The results showed a statistically significant decrease of the activities of alkaline phosphatase and beta-glutamyl transferase in bronchial aspirate from patients with bronchogenic malignant tumors in relation to normal subjects. This finding could be explained by the 'fetalism' principle, which states that the quantitative pattern of enzymes of immature human tissues resembles those of neoplastic tissues.