Dementia and the Risk of Periodontitis: A Population-Based Cohort Study.

Dementia and Alzheimer's disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score-matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score-matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent (P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.

Amylin, a pancreatic peptide, and amyloid-beta peptides (Aß), a major component of Alzheimer's disease (AD) brain, share similar ß-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aß in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aß1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aß in the serum, the magnitude of which is proportionate to the amount of Aß in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aß than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aß1-42 as well as Aß1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aß from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aß in blood. As naturally occurring amylin may play a role in regulating Aß in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

Non-rigid consistent registration of 2D image sequences.

We present a novel algorithm for the registration of 2D image sequences that combines the principles of multiresolution B-spline-based elastic registration and those of bidirectional consistent registration. In our method, consecutive triples of images are iteratively registered to gradually extend the information through the set of images of the entire sequence. The intermediate results are reused for the registration of the following triple. We choose to interpolate the images and model the deformation fields using B-spline multiresolution pyramids. Novel boundary conditions are introduced to better characterize the deformations at the boundaries. In the experimental section, we quantitatively show that our method recovers from barrel/pincushion and fish-eye deformations with subpixel error. Moreover, it is more robust against outliers--occasional strong noise and large rotations--than the state-of-the-art methods. Finally, we show that our method can be used to realign series of histological serial sections, which are often heavily distorted due to folding and tearing of the tissues.

Effects of alpha-tocopheryl acetate and beta-carotene dietary supplementation on the antioxidant enzymes, TBARS and sensory attributes of turkey meat.

1. The aim of the study was to evaluate the effects of alpha-tocopheryl acetate (50 mg/kg) and beta-carotene (15 mg/kg) dietary supplementation on the oxidative status of raw turkey breast and leg muscles assessed by thiobarbituric acid test values, the vitamin E levels and the antioxidant enzyme activities. In parallel, a quantitative descriptive sensory analysis was carried out on cooked, stored and reheated samples. 2. Vitamin E was present in sufficient quantity to reduce oxidation, since iron-induced reactive substances (TBARS) were significantly lower in antioxidant-supplemented treatments. The results suggested that the presence of beta-carotene in the diet limits the accumulation of alpha-tocopherol in turkey muscles. 3. In the present study, there was no conclusive relationship between dietary antioxidant supplementation and endogenous antioxidant enzyme activities. 4. Sensory evaluation showed that a longer supplementation time and dose may be necessary in turkeys to prevent meat from rancidity and warmed-over flavour (WOF). Leg pastiness and stringiness were modified by dietary antioxidant supplementation, indicating the possible synergism between antioxidants and cysteine proteinases in the perception of meat quality. 5. Given the modern trends that lead consumers to increase their consumption of poultry meat, it would be interesting to evaluate the commercial potential and cost effectiveness of routine dietary antioxidant supplementation.

The combined effects of alpha-tocopheryl acetate supplementation and enrofloxacin administration on oxidative stability of turkey meat.

1. The combined effects of dietary supplementation of vitamin E and enrofloxacin administration on the oxidative stability of turkey meat were assessed. 2. Enrofloxacin concentrations found in muscles and liver samples from turkeys receiving 200 g/kg of alpha-tocopheryl acetate plus 50 mg/kg of enrofloxacin without a withdrawal period were higher than those of samples administered with 50 mg/kg of enrofloxacin alone. Similarly, meat samples from turkeys receiving 50 mg/kg of enrofloxacin with withdrawal plus 200 mg/kg of alpha-tocopheryl acetate showed a significantly lower vitamin E accumulation than meat samples of the treatment with enrofloxacin without withdrawal plus vitamin E. 3. The results indicated an interaction between the antioxidant and the antibiotic in their effects on oxidation susceptibility and the abiotic safety of meat from turkeys fed on supplemented diets. A mutual stabilisation of both compounds by reducing the effects of free radicals or by affecting the absorption of the compounds is suggested.

Sangrado de riesgo vital en un recién nacido hijo de madre tratada con rifampicina / Life-threatening hemorrhage in the neonate of a rifampicin-treated mother

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Tratamiento antimicrobiano de las infecciones bronquiales en los servicios de urgencias hospitalarios / Antimicrobial treatment of bronchial infections in hospital emergency rooms

Objetivo: Analizar los hábitos de prescripción de antimicrobianos en los niños atendidos en servicios de urgencias hospitalarios y diagnosticados de infecciones bronquiales. Métodos: Estudio descriptivo de una muestra aleatoria de niños diagnosticados de bronquitis aguda y bronquiolitis en los servicios de urgencias de 11 hospitales españoles. Se recogió información sobre el tipo de infección bronquial diagnosticada y el tratamiento antimicrobiano prescrito mediante un cuestionario estructurado. Se evaluó la idoneidad del tratamiento prescrito según un patrón de referencia elaborado mediante la revisión de las evidencias científicas y la opinión de un grupo de expertos. Resultados: Se seleccionaron 731 niños, 531 (73 por ciento) diagnosticados de bronquitis aguda y 200 (27 por ciento) de bronquiolitis, y se prescribió un tratamiento antimicrobiano a 234 (32 por ciento; intervalo de confianza del 95 por ciento [IC 95 por ciento], 29-35). Los antimicrobianos más prescritos fueron las aminopenicilinas, en 138 niños (19 por ciento; IC 95 por ciento, 16-22), las cefalosporinas en 54 (7 por ciento; IC 95 por ciento, 5-9) y los macrólidos en 45 (6 por ciento; IC 95 por ciento, 4-8). El tratamiento prescrito fue inadecuado en el 26 por ciento (IC 95 por ciento, 23-29) de los casos (31,5 por ciento [IC 95 por ciento, 27-35] en las bronquitis aguda y 11,5 por ciento [IC 95 por ciento, 7-16] en las bronquiolitis). Se observó una gran variabilidad en el uso inadecuado de los antimicrobianos entre los distintos hospitales, tanto en las bronquitis agudas (14-80 por ciento) como en las bronquiolitis (0-71 por ciento). Conclusión: Se prescribe un tratamiento antimicrobiano inadecuado en una proporción relevante de los niños con infecciones bronquiales atendidos en los servicios de urgencias hospitalarias, aunque existe una gran variabilidad interhospitalaria. Es necesario desarrollar programas de mejora de la calidad de la prescripción de antimicrobianos que combinen medidas reguladoras y educativas dirigidas a los profesionales sanitarios y a la población (AU)

[Antimicrobial treatment of bronchial infections in hospital emergency rooms]. / Tratamiento antimicrobiano de las infecciones bronquiales en los servicios de urgencias hospitalarios.

OBJECTIVE: To analyze antimicrobial prescribing habits in children diagnosed with bronchial infections in hospital emergency rooms. METHODS: A descriptive study was performed in a random sample of children diagnosed with acute bronchitis and bronchiolitis in the emergency rooms of 11 Spanish hospitals. Information about the type of bronchial infection diagnosed and the antimicrobial treatment prescribed was gathered. The appropriateness of antibiotic prescriptions was assessed by comparing clinical practice in the use of antibiotics for bronchial infections with consensus guidelines developed for this study. RESULTS: A total of 731 children were selected. The diagnosis was acute bronchitis in 531 (73 %) and bronchiolitis in 200 (27 %). Antimicrobial treatment was prescribed to 234 children (32 %; 95 % CI: 29-35 %). The most commonly prescribed antimicrobials were the aminopenicillins in 138 children (19 %; 95 % CI 16-22 %), cephalosporins in 54 (7 %; 95 % CI 5-9 %) and macrolides in 45 (6 % 95 % CI 4-8 %). The prescribed treatment was inappropriate in 26 % (95 % CI 23-29 %) of patients [31.5 % (95 % CI 27-35 %) of cases of acute bronchitis and 11.5 % (95 % CI 95 % 7-16 %) of cases of bronchiolitis]. Wide variability was observed in the inappropriate use of antimicrobial agents among the different hospitals, both in acute bronchitis (14-80 %) and in bronchiolitis (0-71 %). CONCLUSION: Inappropriate antimicrobial treatment is prescribed to a considerable proportion of the children with bronchial infections attended in hospital emergency rooms, although there is wide variability among different hospitals. Programs to improve the quality of antimicrobial prescription should be developed. These should combine regulatory and educational measures directed at health professionals and the general public.

Influence of enrofloxacin administration and alpha-tocopheryl acetate supplemented diets on oxidative stability of broiler tissues.

The objective of this study was to assess the oxidative stability and presence of antibiotic residues in tissues of broilers fed diets supplemented with alpha-tocopheryl acetate and treated with enrofloxacin. The activities of antioxidant enzymes and antibiotic concentrations in chicken breast, leg, and liver were determined. Iron-induced TBA-reactive substances (TBARS) and vitamin E were evaluated in muscles. The antioxidant effectiveness of vitamin E was reflected by TBARS values being lower in antioxidant-supplemented treatments than in the other dietary groups. On the other hand, antioxidant enzyme activities were not substantially affected by dietary treatments. The concentration of enrofloxacin in tissues was considerable, even after withdrawal 12 d before slaughter. Contrary to the findings in previous studies, enrofloxacin was not extensively metabolized to ciprofloxacin. Supplementation of the diet with 100 mg/kg of alpha-tocopheryl acetate did not have a significant effect on the level of antibiotic found in breast muscle samples. When comparing treatments without antibiotic withdrawal time, alpha-tocopheryl acetate supplementation led to a significant decrease in enrofloxacin level in leg and liver samples. These results showed that mutual interactions between different molecules could modify the drug residues in the tissue, which should be taken into account when considering the drug administration and the establishment of a correct withdrawal time.

Un registro europeo de ensayos clínicos en niños / A European registry of clinical trials in children

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Automatic registration of serial mammary gland sections.

We present two methods for automatic registration of microscope images of consecutive tissue sections. They represent two possibilities for the first step in the 3-D reconstruction of histological structures from serially sectioned tissue blocks. The goal is to accurately align the sections in order to place every relevant shape contained in each image in front of its corresponding shape in the following section before detecting the structures of interest and rendering them in 3D. This is accomplished by finding the best rigid body transformation (translation and rotation) of the image being registered by maximizing a matching function based on the image content correlation. The first method makes use of the entire image information, whereas the second one uses only the information located at specific sites, as determined by the segmentation of the most relevant tissue structures. To reduce computing time, we use a multiresolution pyramidal approach that reaches the best registration transformation in increasing resolution steps. In each step, a subsampled version of the images is used. Both methods rely on a binary image which is a thresholded version of the Sobel gradients of the image (first method) or a set of boundaries manually or automatically obtained that define important histological structures of the sections. Then distance-transform of the binary image is computed. A proximity function is then calculated between the distance image of the image being registered and that of the reference image. The transformation providing a maximum of the proximity function is then used as the starting point of the following step. This is iterated until the registration error lies below a minimum value.

[Drug utilization and recommended conditions for use in children]. / Utilización de medicamentos y condiciones de uso recomendadas en pediatría.

BACKGROUND: Studies carried out in other countries show that drugs are used in children outside the approved conditions, in a context in which investigation, information and authorization of medications in the pediatric population are scarce. OBJECTIVES: To evaluate the conditions of drug use recommended in children and variability in sources of drug information. METHODS: We performed a descriptive, retrospective study. Data on medication consumption in 1997 were obtained from a pediatric university hospital. Information on conditions of drug use in children was analyzed using a Spanish catalog of medications. This information was compared with that of a North American catalog for international reference. RESULTS: Most of the drugs used were of unrestricted (43; 47 %) or restricted (26; 28 %) pediatric use, but drugs that are not recommended (8; 9 %) or those with unspecified conditions of use in children were also used (15; 16 %). Approximately 12 % of the drugs were not identified in the North American catalog; of the remaining drugs, 60 % were of unrestricted pediatric use, 35 % of restricted use and 5 % were not recommended. CONCLUSIONS: A substantial proportion of drugs administered to hospitalized children are not recommended or their possible use in this population is not specified. It is worth encouraging research, having sources of information that help to make decisions, especially in conditions that have not been approved, and adapting regulatory attitudes, as far as possible, to the evidence and therapeutic needs.

Utilización de medicamentos y condiciones de uso recomendadas en pediatría / Drug utilization and recommended conditions for use in children

Antecedentes: Estudios realizados en otros países indican que en niños se utilizan fármacos en condiciones distintas a las aprobadas, en un contexto en que son escasas la investigación, información y autorización de medicamentos en población pediátrica. Objetivos: Evaluar las condiciones de uso recomendadas en pediatría para los fármacos utilizados en niños y la variabilidad de las fuentes de información sobre éstos. Métodos: Estudio descriptivo y retrospectivo. Se seleccionaron los datos de consumo de medicamentos en un hospital universitario pediátrico durante el año 1997. Se analizó la información sobre las condiciones de uso en pediatría de los fármacos utilizados a partir de un catálogo de medicamentos español. Esta información se comparó con la de un catálogo norteamericano de referencia internacional. Resultados: La mayor parte de los fármacos utilizados fueron de uso pediátrico no restringido (43 [47%]) o restringido (26 [28%]), pero también se utilizaron fármacos no recomendados (8 [9%]) o para los que no se especificaban condiciones de uso en niños (15 [16 %]). Alrededor del 12% de los fármacos no se identificaron en el catálogo norteamericano; de los restantes, el 60% de los fármacos fueron de uso pediátrico no restringido, el 35% de uso restringido y el 5% no recomendados. Conclusiones: En niños hospitalizados, una proporción relevante de los fármacos que se utilizan no se recomiendan o no se especifica su posible uso en población pediátrica. Sería conveniente incentivar la investigación, disponer de fuentes de información sobre terapéutica que ayuden a tomar decisiones, sobre todo en las condiciones no aprobadas, y que la actitud reguladora se ajuste en la medida de lo posible a las evidencias y necesidades terapéuticas (AU)

Profilaxis de las infecciones por el virus respiratorio sincitial con palivizumab / Prophylaxis of respiratory syncytial virus infections with palivizumab

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Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression.

Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.