Cognition and the risk of eating disorders in Spanish adolescents: the AVENA and AFINOS studies.

UNLABELLED: Eating disorders (ED) can arise from a combination of biological and psychological factors. Some studies suggest that intellectual factors might be important in the development of ED, although the evidence is still scarce. The aim of this study was to examine the association between cognition measurements (cognitive performance and academic achievement) and the risk of developing ED in adolescents considering their weight status. The sample consisted of 3,307 adolescents (1,756 girls), aged 13-18.5 years, who participated in the AVENA (n = 1,430; 783 girls) and AFINOS (n = 1,877; 973 girls) studies. Cognitive performance was measured by the TEA test in the AVENA study, and academic achievement was self-reported in the AFINOS study. ED risk was evaluated in both studies by using the SCOFF questionnaire. Body mass index was calculated to classify adolescents as non-overweight or overweight (including obesity). Overweight adolescents showed a higher risk of developing ED than non-overweight ones in both studies. In the AVENA study, overweight boys with low performance in reasoning ability showed increased risk of ED (p = 0.05). In the AFINOS study, overweight boys with low academic performance in physical education and non-overweight girls with low academic achievement in all the areas analyzed showed higher risk of ED than their peers (all p < 0.05). CONCLUSION: No association between cognitive performance and ED risk was found in adolescents, while academic achievement was associated with ED risk, especially in non-overweight girls. The non-cognitive traits that accompany academic achievement could influence the likelihood of developing ED in these girls.

Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents.

OBJECTIVE: To evaluate the effects of a multidisciplinary obesity treatment programme on fecal microbiota composition and immunoglobulin-coating bacteria in overweight and obese adolescents and their relationship to weight loss. DESIGN: Longitudinal intervention study based on both a calorie-restricted diet (calorie reduction=10-40%) and increased physical activity (calorie expenditure=15-23 kcal/kg body weight per week) for 10 weeks. PARTICIPANTS: Thirty-nine overweight and obese adolescents (BMI mean 33.1 range 23.7-50.4; age mean 14.8 range, 13.0-16.0). MEASUREMENTS: BMI, BMI z-scores and plasma biochemical parameters were measured before and after the intervention. Fecal microbiota was analyzed by fluorescent in situ hybridization. Immunoglobulin-coating bacteria were detected using fluorescent-labelled F(ab')2 antihuman IgA, IgG and IgM. RESULTS: Reductions in Clostridium histolyticum and E. rectale-C. coccoides proportions significantly correlated with weight and BMI z-score reductions in the whole adolescent population. Proportions of C. histolyticum, C. lituseburense and E. rectale-C. coccoides dropped significantly whereas those of the Bacteroides-Prevotella group increased after the intervention in those adolescents who lost more than 4 kg. Total fecal energy was almost significantly reduced in the same group of adolescents but not in the group that lost less than 2.5 kg. IgA-coating bacterial proportions also decreased significantly in participants who lost more than 6 kg after the intervention, paralleled to reductions in C. histolyticum and E. rectale-C. coccoides populations. E. rectale-C. coccoides proportions also correlated with weight loss and BMI z-score reduction in participants whose weight loss exceeded 4 kg. CONCLUSIONS: Specific gut bacteria and an associated IgA response were related to body weight changes in adolescents under lifestyle intervention. These results suggest interactions between diet, gut microbiota and host metabolism and immunity in obesity.

[Rare diseases: medicine's challenge in the XXI Century]. / Enfermedades raras: el reto de la medicina en el siglo XXI.

Rare diseases (RD) are receiving increasing attention within both the scientific community and society in general. Many RDs are diagnosed during paediatric age and affect the patient throughout his life, but they can also be diagnosed during adult age. Advances in the biochemical, molecular and genetic diagnosis of these diseases are proving essential in improving clinical understanding and therapeutic possibilities. However, their low prevalence makes it difficult to develop suitable medicines for treatment and it is necessary to implement specific social and health protection programs for these medicines, which are called orphan medicines (OM). In general these serious, chronic diseases involving a high degree of disability are difficult to diagnose. For better diagnosis and monitoring it is necessary to develop reference units at the state level that will improve our knowledge of these pathologies. RDs have a direct repercussion on both the family, which in many cases becomes the carer, and on society, which must develop specific social, health and educational programs to support these patients. In short, RDs form a significant challenge of coordination for the scientific community and for society given their significant specific weight in the development of health care in our setting.

[Rare diseases in paediatrics]. / Enfermedades raras en pediatría.

Few areas of paediatric care are as susceptible to the revision of lines of action, and require such professional training, as the care of the child with a rare disease (RD) and his/her family, especially if there are malformations. The lifelong impact, which many RDs entail, make continuous monitoring of the child compulsory, centred both on the evolutionary aspects of the RD and on the family's adaptation to the problem. Besides the sad reality they confront, the parents must frequently make immediate decisions on medical or surgical treatment for their child, or face a lethal or disabling condition that "robs" them of their expectations. Only suitable care for each of the numerous problems faced by these children and their families helps to minimise the potential handicap associated with RDs. In spite of the unquestionable complexity involved in exploring this field, the paediatrician must acquire knowledge of these diseases in order to ground his involvement in the diagnosis and monitoring of these patients. Abstention by the paediatrician in the face of this responsibility would have a negative effect on the care of these patients, which he must share with the corresponding specialists.

[Genetically based diseases]. / Enfermedades de base genética.

Genetics is one of the greatest scientific advances of the XX century, which begins with the rediscovery of Mendel's laws and culminates in the elaboration of the first "draft" of the complete sequence of the human genome. Genetics employs different research strategies, such as the study of twins and adoption, investigating the influence of genetic and environmental factors, and strategies for identifying specific genes (molecular genetics). Besides the significant degree of disability they generate, the social impact of hereditary diseases is enormous, due to their potentially recurrent character in the same family and the high socio-health cost deriving from the enormous care burden they require. The diagnosis of hereditary diseases presents very significant differentiating characteristics since the result of a genetic diagnosis has effects not only on the patient but also on related individuals. Thus the unit of study in genetic diagnosis is the family and the whole process of diagnosis involves family research. It is also useful to bear in mind that the protocols of diagnosis are developed in parallel with the basic research and in general are hardly standardised. The results obtained in genetic studies and the type of information provided to the patient and his family must be qualified within the process of "genetic counselling".

[Needs in rare diseases during paediatric age]. / Necesidades en las enfermedades raras durante la edad pediátrica.

All rare diseases present a common set of challenges to the sufferers and their families: diagnosis, dealing with symptoms, health information, obtaining helpful medical care, availability of medications, disability and emotional impact. Children with rare disorders are an important population from health care services, and social services perspectives, and families are providing long-term care for these chronically ill children. The impact of rare disorders in children is far-reaching, extending beyond the child to all those with whom he/she has contact. Multiple facets of life are affected including social an family relationships, economical well-being and activities of daily living. The assessment of needs for rare disorders treatment is a critical step in providing high quality care and achieving patients' and families' satisfaction. Findings from different studies show that people with rare diseases have medical and social needs. Social needs are becoming more relevant in developed countries where health care services, even with limitations, have greater availability than social services. Furthermore, it seems that health care and social services for persons with rare diseases need to be improved to address the patients' needs and to provide better support to families. Validated tools with good psychometric properties are still needed to assess quality of care on the basis of patients and family needs.

Protection of the peptide glutathione by complex formation with alpha-cyclodextrin: NMR spectroscopic analysis and stability study.

The main objective of this work was to investigate the complexation mechanism of the tripeptide glutathione with alpha-cyclodextrin (alpha-CyD). The final purpose was to explore the possibility of using this complexation approach for preserving the stability of this peptide in all biological environments relevant for oral drug delivery. The complexes between the peptide and alpha-CyD were formed in aqueous solution and the complexation mechanism was investigated using different (1)H NMR experimental approaches. The resulting complexes were also studied with respect to their ability to protect the peptide against proteolytic degradation by the exopeptidase, gamma-glutamyltranspeptidase. The NMR experiment, 1D-saturation transfer NOE difference (STD), evidenced the interaction between alpha-CyD and glutathione. The binding constants, calculated by a titration method, were in the range of 55-70 M(-1) at 25 degrees C and in the range 68-72 M(-1) at 37 degrees C. Moreover, from the 1D-pulse field gradient spin echo-transverse-rotating frame nuclear Overhauser (PFGSE-T ROESY) spectra it was concluded that alpha-CyD binds preferably to the l-glutamate (side chain) moiety of glutathione, leaving the glycine residue exposed to the external medium. This result was consistent with those of the in vitro stability study, which indicated that the degradation of glutathione was markedly reduced to the half in 2h upon inclusion in alpha-CyD. Overall, these results show the possibility of protecting specific peptide groups by their inclusion in CyDs as well as the utility of NMR experiments for the understanding of this stabilization strategy.

A comparative study of the potential of solid triglyceride nanostructures coated with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery.

We have previously reported the formation and characterization of poly(ethylene glycol) (PEG)-coated and chitosan (CS)-coated lipid nanoparticles. In the present work our goal was to study the interaction of these surface-modified lipid nanoparticles with Caco-2 cells and to evaluate the potential of these nanostructures as oral delivery systems for salmon calcitonin (sCT). The interaction of rhodamine-loaded nanoparticles with the Caco-2 cell monolayers was evaluated quantitatively and qualitatively by confocal laser scanning microscopy and fluorimetry, respectively. The ability of these nanoparticles to reversibly enhance the transport of hydrophilic macromolecules through the monolayers was investigated by measuring the transepithelial electric resistance and the permeability to Texas Red-dextran. Finally, in vivo studies of the response to sCT-loaded nanoparticles were performed in rats. The results showed that the association of rhodamine-loaded nanoparticles to the Caco-2 cell monolayer was independent of the surface coating of the nanoparticles (CS-coated versus PEG-coated nanoparticles). However, while PEG-coated nanoparticles did not affect the permeability of Caco-2 monolayers, CS-coated nanoparticles produced a dose-dependent reduction in the transepithelial electric resistance, simultaneously to an enhanced dextran transport. The results obtained following oral administration of sCT-loaded CS-coated nanoparticles to rats showed a significant and prolonged reduction in the serum calcium levels as compared to those obtained for control (sCT solution). In contrast, the hypocalcemic response of sCT-loaded PEG-coated nanoparticles was not significantly different of that provided by the control (sCT solution). Therefore, these results indicate that the surface composition of the particles is a key factor in the improvement of the efficiency of oral sCT formulations. Moreover, the encouraging results obtained for CS-coated nanoparticles underline their potential as carriers for peptide delivery.

[Breakfast and snack of schooled adolescents in Santander]. / Desayuno y almuerzo de los adolescentes escolarizados de Santander.

OBJECTIVE: To study the breakfast model and food intake at mid-morning (snack) in schooled adolescents at Santander city. SUBJECTS: A cross-sectional study was performed analyzing a sample of 403 adolescents: 232 girls (58%; 95% CI: 52%-62%) and 171 boys (42%; 95% CI: 38%-48%), with ages between 12 and 19 years, schooled at 12 second degree education centers of Santander, by means of a closed questionnaire and a recall 24 hours later. RESULTS: Five percent (95% CI: 3.1%-7.6%) of the adolescents referred neglecting breakfast. The most consumed foods were milk (47%; 95% CI: 42%-52%), chocolate milk (40%; 95% CI: 36%-45%), and cookies (45%; 95%CI: 36%-45%). On the other hand, 63% of adolescents consume whole milk (95% CI: 58%-70%), 21% semi-skimmed milk (95%CI: 17%-26%), and 11% skimmed milk (95% CI: 8%-15%). A decreasing lineal tendency in whole milk consumption is observed and a parallel increase in consumption of milks with a lower fat content as the academic year of adolescents advances (Armitage's chi-square test for lineal tendency = 2.32; p = 0.02). Boys consume an average of 3.0 (SD = 1.35) different foods during breakfast and girls 2.4 (SD = 1.20). Forty-three percent (95% CI: 38%-48%) of adolescents have a snack, which means that 2% of adolescents do not have breakfast or a snack (95% CI: 1%-4%). Breakfast represents 18% (95% CI: 16%-19%) of the total daily energy intake, whereas for snack, this percentage is 16% (95% CI: 14%-17%). CONCLUSION: it is necessary to promote consumption of a healthy breakfast and snack that provide an appropriate quantitative and qualitative intake.

Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients.

Cutaneous vasculitis (CV), a condition characterized by palpable purpura and nonspecific histopathologic findings, presents a diagnostic and therapeutic challenge because it may be a primary disorder or it may be a cutaneous manifestation of another entity, such as systemic necrotizing vasculitis, connective tissue disease, systemic bacterial infection, or malignancy. We studied 303 unselected patients (172 adults and 131 children) with CV to assess the disease associations and etiologic factors, to identify the frequency of primary and secondary CV in different age-groups, and to characterize features that help to distinguish between primary and secondary CV. Of the 131 children, 130 had primary CV: Henoch-Schönlein purpura (HSP) in 116 and hypersensitivity vasculitis (HV) in 14. In contrast, of the 172 adults, only 120 had primary CV: HSP in 39, HV in 70, and essential mixed cryoglobulinemia in 11. CV was a manifestation of systemic necrotizing vasculitis in 23 adults (polyarteritis nodosa in 17, Wegener granulomatosis in 4, and Churg-Strauss syndrome in 2). CV was secondary to other processes in 29 adults: in 20 patients CV was associated with connective tissue disease or another autoimmune or rheumatic disease, in 5 patients CV was a manifestation of severe bacterial infection, especially bacterial endocarditis (4 cases), and in the other 4 patients CV was the presenting symptom of an underlying malignancy. The patients for whom CV was a manifestation of systemic necrotizing vasculitis or secondary to a connective tissue disease, severe bacterial infection, or malignancy had clinical and laboratory data suggestive of the associated disorder. The clinical picture and outcome of primary CV in both children and adults were benign. By contrast, the prognosis of patients with CV in the context of systemic necrotizing vasculitis or secondary to other entities depended on the primary process. Given the different disease association in children and adults, we propose a simple diagnostic workup in children with CV. By contrast the diagnostic approach in adults with CV should be more cautious and the workup more extensive. The early differentiation between primary CV, secondary CV, and CV presenting as a symptom of systemic necrotizing vasculitis, especially in adults, is of paramount importance for an adequate diagnosis and appropriate treatment.

Clinical features and outcome of 95 patients with hypersensitivity vasculitis.

PURPOSE: To evaluate the clinical features and outcome of patients with isolated hypersensitivity vasculitis (HV). PATIENTS AND METHODS: Retrospective study of patients with cutaneous vasculitis followed up at a University Hospital from 1975 to 1994. Patients with vasculitis secondary to collagen vascular diseases, neoplasia, or major infections were excluded. Patients were classified as HV according to the differential criteria proposed by Michel et al (J Rheumatol. 1992;19:721-728). RESULTS: Ninety-five patients were classified as HV. The mean age was 42.7 +/- 21.7 years, with similar disease frequency in both sexes. In 43 patients, the precipitating event was drug therapy, either alone or as a treatment for a coexistent infection, usually an upper respiratory tract infection. The most frequent clinical manifestation was palpable purpura followed by joint symptoms. Systemic involvement was infrequent: 7 patients had nephropathy, manifested almost exclusively by microhematuria, and 5 patients had gastrointestinal symptoms. In 54 subjects the vasculitis did not require treatment; 26 patients were treated with NSAIDs, and 14 required corticosteroids (associated to immunosuppressive agents in 2 of them). After a mean follow-up of 15.5 +/- 28.9 months (median 6), only 2 patients had slight renal impairment, whereas the remaining had a complete recovery. CONCLUSION: Hypersensitivity vasculitis is usually a benign syndrome, often secondary to drugs or infections, or both. Its main clinical manifestations are skin and joint symptoms. The systemic involvement is scarce and its prognosis is excellent.

Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary stenosis.

Based on genetic variability, structural differences in the glycoprotein IIb/IIIa platelet receptor for adhesive proteins result in individual differences in the thrombogenicity of platelets. Recent studies suggest a controversial association between a genetic polymorphism of the glycoprotein IIIa gene (PlA2) and the risk of coronary artery disease. In our study, the prevalence of the PlA2 allele in a group of patients undergoing percutaneous coronary revascularization was 37%, a value significantly higher than in controls [13%, odds ratio (OR) = 3.93, 95% CI, 1.84 to 8.53] suggesting a significant association between this polymorphism and documented coronary stenosis, which is strongest among <60 years old patients (OR = 12.30, 95% CI, 2.98 to 70.93). This polymorphism represents an inherited risk factor for severe cardiovascular disease due to coronary occlusion.

Variables affecting BMI evolution at 2 and 5 years after vertical banded gastroplasty.

BACKGROUND: Vertical banded gastroplasty (VBG) has been found to result in significant reduction in body mass index (BMI) during the first postoperative year. We investigated the impact of some intrinsic and extrinsic factors on long-term BMI evolution in morbidly obese patients who underwent VBG, with the aim of establishing a long-term weight-loss prognosis. METHODS: 67 consecutive morbidly obese patients who underwent VBG were followed for 2 years; of these, 34 were followed 3 more years, for a total follow-up of 5 years. BMI was monitored and correlated with demographic (preoperative BMI, obese relatives, age and gender) and lifestyle variables (physical activity, habitual dietary transgression and occupational status). RESULTS: Global BMI fell from 47.5 at the time of the intervention to 32.1 when patients were examined 12 months after surgery. From the second year, an upward trend was observed, and at 5 years, mean BMI was above 35, considered in the high-risk range. Modifiable variables affecting lifestyle have shown significantly favorable effects on BMI evolution. Among intrinsic variables, BMI before surgery and obese parents also affect long-term evolution. CONCLUSION: Different variables should be considered in order to establish a long-term weight-loss prognosis for each patient, thus making it possible to act more specifically on modifiable variables.

[Blood coagulation, genetics and post-angioplasty restenosis]. / Coagulación, genética y reestenosis postangioplastia.

Throughout the last few decades, different factors have been related to coronary stenosis which is clinically evidenced by coronary heart disease, the leading cause of death in developed countries. Different experimental models have contributed towards defining some of these factors, and to an understanding of the physiopathology of the atherosclerotic lesion. The genetic basis related to individual responses to the same event is currently being established. As endothelial injury reparative mechanisms are fundamental in atherosclerosis pathogeny, patients who experiment restenosis after undergoing revascularization procedures are useful human models in the study of these processes. We review from the literature the genetic factors related to thrombus formation, which may be associated with restenosis after percutaneous transluminal coronary angioplasty, in order to define the most suitable anticoagulant therapy for each patient. We refer to the recently characterized gene for the platelet receptors and its relationship with fibrinogenous, factor Xa, PAI-I, and the involvement of apolipoprotein (a) in the coagulation process.

Five year trends on total and abdominal adiposity in Spanish adolescents.

OBJECTIVE: To assess five years trends in total and abdominal fat in Spanish adolescents. DESIGN: Two cross-sectional studies: adolescents from the city of Zaragoza (Spain) assessed during 2001-2002 and 2006-2007. SUBJECTS: 399 adolescents in 2001-02 and 392 adolescents in 2006-07. MAIN OUTCOME MEASUREMENTS: Socio-economic status was assessed using the education level of both parents. A complete anthropometric assessment was performed in both surveys using the same methodology: weight, height, skinfold thickness (biceps, triceps, subscapular, suprailiac, thigh and calf) and circumferences (waist and hip). The body mass index (BMI) and the sum of 6 skinfold thicknesses were calculated. Body fat percentage (BF%) was also calculated by the formulas described by Slaughter et al. RESULTS: After adjusting for age and pubertal status, only females showed a significantly decrease in weight, BMI and waist circumference, and a significant increase in the sum of 6 skinfolds (all P < 0.05 and Cohen's d ≥ 0.25) in 2006-2007, when compared to values obtained in 2001-2002. Males did not show any significant change between the two surveys. Concerning centile values, a slight general reduction was observed in weight, BMI and waist circumference for both males and females. On the contrary, the sum of 6 skinfolds and the BF% were higher in 2006-2007 than in 2001-2002. CONCLUSION: According to these results, there might be a levelling-off in the trends of BMI, BF% and waist circumference in male adolescents from Zaragoza. In females, despite a trend towards higher body fat mass, there was a trend towards lower BMI and waist circumference values.

Novel drug nanocarriers combining hydrophilic cyclodextrins and chitosan.

The aim of this study was to explore the possibility of obtaining nanoparticles (NPs) containing high amounts of cyclodextrin (CD) derivatives such as carboxymethyl-ß-CD and sulphobutyl ether-ß-CD. The rationale used was to combine the drug solubilizing and stabilizing properties of cyclodextrins (CDs) with the mucoadhesive properties of chitosan (CS) in a unique nanoparticulate drug delivery system. The size of the resulting NPs was affected by the nature of the CDs, ranging between 275 and 550 nm, whereas the zeta potential of the NPs was always positive and close to +35 mV. The positive zeta values, together with the results from NMR studies, suggest that CS is the major compound on the surface of the NPs, while CD molecules are strongly associated with the NP matrix. The empirical composition of the NPs was quantified by elemental analysis and the results indicated that the amount of CD associated with the NPs was strictly dependent on its electrostatic charge. Finally, in vitro stability studies indicated that the presence of CDs in the NP structure can prevent the aggregation of this nanometric carrier system in simulated intestinal fluid. Overall, this new type of NP represents an attractive drug delivery platform of particular interest for the oral administration of drugs with low bioavailability.

[Poststreptococcal glomerulonephritis]. / Glomerulonefritis aguda postestreptocócica.

Acute poststreptococcal glomerulonephritis is one of the best defined renal diseases and it is the commonest form of acute glomerulonephritis in children. Antigen-antibody complexes formed in the circulation or "in situ" seem to play an important role in the pathogenesis and even though antiglobulins have recently been incriminated, there is still controversy over the nature of the antigen/s involved. Usually the clinical picture is very characteristic, but in those cases of atypical presentation mainly in those without urinary abnormalities, the diagnosis could be resolved by demonstration of well defined histological lesions. Although it is generally agreed upon, on the basis of clinical observations, that recovery from acute glomerulonephritis generally occurs in children, confusion still exists concerning the precise frequency with which chronicity may happen in this disease. There is no specific treatment for the immunological processes but symptomatic therapy has considerably reduced early mortality.