RESUMEN
BACKGROUND: The radiological evaluation of the upper gastrointestinal tract (GI tract) is a diagnostic challenge. Although endoscopy has pushed radiographic methods into the background, these methods continue to play a key role in the diagnosis of dysphagia. In addition, cross-sectional imaging (computed tomography, magnetic resonance imaging) is increasingly used in complex clinical cases to evaluate surrounding tissue changes. METHODS: By combining conventional double-contrast techniques with a video recording, the entire upper GI tract can be assessed both anatomically and functionally in one examination procedure. CONCLUSION: In addition to the clarification of swallowing disorders, videofluoroscopy can be used to assess postoperative control after antireflux and bariatric surgery. To obtain optimal results in video swallowing studies, the procedure should be adapted to the individual symptoms of the patient.
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Tracto Gastrointestinal Superior , Endoscopía , Humanos , Imagen por Resonancia Magnética , Radiografía , Tomografía Computarizada por Rayos X , Tracto Gastrointestinal Superior/diagnóstico por imagenRESUMEN
OBJECTIVES: This is an evaluation of an ongoing inpatient smoking cessation program available in Austria and aims to show to what extent even heavy nicotine dependent smokers can benefit from a three-week inpatient therapy. STUDY DESIGN: A particular focus lies on analyzing the benefits and changes in lifestyle and sense of well-being. METHODS: 270 initially heavy nicotine dependent smokers are observed for a one year period consisting of recruitment, therapy and two post-therapy follow-up visits; post program smokers are compared to post program ex-smokers. RESULTS: 12 month post-therapy, 42.6% of participants are identified by carbon monoxide-verifications as ex-smokers, 34% as smokers and the remaining did not attend follow-up visits. Significant changes in lifestyle satisfaction are reported by ex-smokers compared to still smokers. CONCLUSIONS: Convincing heavy dependent nicotine smokers that significant changes in lifestyle satisfaction can be expected as part of a successful cessation process should lead to enough motivation for these individuals to seek such inpatient smoking cessation program.
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Pacientes Internos/psicología , Estilo de Vida , Satisfacción Personal , Cese del Hábito de Fumar/estadística & datos numéricos , Prevención del Hábito de Fumar , Tabaquismo/prevención & control , Monóxido de Carbono/análisis , Femenino , Estudios de Seguimiento , Humanos , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Fumar/psicologíaRESUMEN
CLINICAL/METHODICAL ISSUE: Colorectal cancer is a major public health challenge in Austria and Germany. As the participation in dedicated colonoscopy screening programs is rather low, the question of alternative methods is raised again and computed tomography (CT) colonography seems to be a gentle alternative with a very high patient acceptance. STANDARD RADIOLOGICAL METHODS: In recent years CT colonography (CTC) has been established besides conventional colonoscopy as a radiological method for the investigation of the entire colon. From axial two-dimensional images three-dimensional images can be generated, allowing a virtual flight through the colon which is why this technique is also known as virtual colonoscopy. METHODICAL INNOVATIONS: The technique of CTC has been improved continuously during recent years. On the one hand the steady decrease in the layer thickness (currently ≤ 1 mm) has improved the resolution of volume data sets and on the other hand there has been significant progress in postprocessing. PERFORMANCE: Numerous studies have recently shown that the significance of CTC in the detection of advanced adenomas is similar to conventional colonoscopy. ACHIEVEMENTS: Meanwhile CT colonography is now a routine investigation method established in both symptomatic and asymptomatic patients (screening). PRACTICAL RECOMMENDATIONS: Study data now clearly show that CTC, as an alternative to conventional colonoscopy, is a powerful method for investigation of colorectal cancer. To achieve good results adequate preparation including fecal tagging, standardized technical procedures during the investigation and expertise in both 2D and 3D reading are essential.
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Colonografía Tomográfica Computarizada/métodos , Colonografía Tomográfica Computarizada/tendencias , Neoplasias Colorrectales/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Austria , Medicina Basada en la Evidencia , Alemania , HumanosRESUMEN
Geriatric patients with acute somatic illness have a high comorbidity of depression and dementia. The following differential diagnoses have to be discerned: pseudodementia in acute depressive states, depression as a risk factor for dementia, and a depressive episode in the early stage of dementia. For both the symptoms and the trigger factors of these differential diagnoses the overlap and the particularities were qualitatively examined in the AIDE-cog (Acute Illness and Depression in Elderly cognition) trial. A second prospective randomized controlled part of the AIDE-cog trial quantitatively evaluated the influence of cognitive impairment in geriatric patients with an acute somatic illness and comorbid depression on the therapeutic effect of cognitive behavioral therapy. A preliminary analysis shows that already in early dementia the therapeutic effects are inferior. Other psychotherapeutic methods that address the remaining cognitive and emotional functions in dementia must be evaluated.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Depresión/diagnóstico , Depresión/epidemiología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
For the first time a vertical-cavity surface-emitting laser (VCSEL) with a single-mode wavelength-tuning over 102 nm in the range of 1550 nm is demonstrated. The fiber-coupled optical output power has a maximum of 3.5 mW and is > 2 mW over the entire tuning range. The sidemode suppression ratios are > 45 dB. The wavelength tuning is achieved with the micro-electro mechanical actuation of a mirror membrane fabricated with surface micro-machining for on-wafer mass production. The mirror membrane consists of low cost dielectric materials (SiOx/SiNy) deposited with low temperature (< 100°C) Plasma Enhanced Chemical Vapor Deposition (PECVD).
RESUMEN
The incidence of clinically significant anastomotic leaks after upper gastrointestinal surgery is approximately 4 % - 20 %, and the associated mortality can be as high as 80 %. Depending on the clinical presentation, the treatment options are surgery, conservative treatment with external drainage, or endoscopic treatment. This report presents 39 cases of clinically apparent anastomotic leaks or fistulas after surgery for upper gastrointestinal cancers that were treated by endoscopy with insertion of fibrin glue alone (n = 24) or with a combination of Vicryl plug and fibrin glue (n = 15). Thirteen of the 15 patients who underwent Vicryl/fibrin treatments showed complete healing of the anastomotic leak or fistula after one to four sessions. Long-term follow-up results are presented. Postoperative upper gastrointestinal fistulas or anastomotic leaks can be managed successfully with low morbidity by means of endoscopic insertion of Vicryl mesh with fibrin glue, thereby avoiding repeated major surgery and its associated risks.
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Fístula del Sistema Digestivo/terapia , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Adhesivo de Tejido de Fibrina/uso terapéutico , Gastrectomía/efectos adversos , Mallas Quirúrgicas , Algoritmos , Anastomosis Quirúrgica/efectos adversos , Fístula del Sistema Digestivo/etiología , Estudios de Seguimiento , Fístula Gástrica/etiología , Fístula Gástrica/terapia , Humanos , Fístula Intestinal/etiología , Fístula Intestinal/terapia , Poliglactina 910 , Complicaciones Posoperatorias , Cicatrización de HeridasRESUMEN
BACKGROUND: The present study examines the causes and surgical management in children who underwent surgery for a mechanical Ileus. PATIENTS: We studied all children up to the age of 18 years who had undergone a surgical intervention for a mechanical ileus between 1.1.1996 and 31.12.2006. 89 children were included in this retrospective study. RESULTS: Of the total of 89 children 15 were newborn (16.9 %), 23 babies (25.8 %), 19 toddlers (21.3 %) and 32 school children (36 %) at the time of the operation. 51 of the 89 children had undergone at least one previous abdominal operation. Intraoperative findings showed the cause for the ileus to be adhesions in 56 and a bowel invagination in the remaining 11 children. Associated malformations were found in 34 children, the most frequent being malformations of the heart and gastrointestinal tract. The most frequent surgical intervention was adhesiolysis in 56 children (62.9 %), followed by the reposition of invaginated intestine in 11 (12.4 %). Bowel resection was necessary in 23 children (25.8 %). CONCLUSION: The risk for developing an ileus due to adhesions increases with the number of previous operations. Surgical intervention for an ileus aims to decompress the overstretched bowel and to restore gastrointestinal flow by removing the mechanical obstruction. One third of the children with an ileus have accompanying malformations. Children with a mechanical ileus should undergo surgery as soon as possible.
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Ileus/etiología , Ileus/cirugía , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Intususcepción/etiología , Intususcepción/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación , Estudios Retrospectivos , Adherencias Tisulares/etiología , Adherencias Tisulares/cirugíaRESUMEN
Thin-section multidetector-row computed tomographic (MDCT) colonography is a powerful tool for detection and classification of colonic lesions. It is based on a helical thin-section (0.75-2 mm) CT dataset of the cleansed and air-distended colon. 2D and 3D projections are prepared and used for image interpretation. Evaluation of CT colonography datasets requires correct perception and interpretation of colonic lesions and filling defects. Various criteria are needed for correct interpretation of filling defects and differentiation between genuine lesions and artifacts. Such defects are characterized by their morphology, their structure, the absorption of contrast medium and their mobility. Knowledge of the morphologic and attenuation characteristics of common colonic lesions and of artifacts is essential for the correct interpretation of a filling defect. This review article summarizes the main imaging features of polyps, diverticula, lipomas, and carcinomas and also of common pseudolesions of the colon.
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Enfermedades del Colon/diagnóstico por imagen , Neoplasias del Colon/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Colonografía Tomográfica Computarizada/métodos , Artefactos , Competencia Clínica , Diagnóstico Diferencial , Diverticulosis del Colon/diagnóstico por imagen , Humanos , Mucosa Intestinal/diagnóstico por imagen , Lipoma/diagnóstico por imagen , Sensibilidad y EspecificidadRESUMEN
Three complete genome sequences of thermophilic bacteria provide a wealth of information challenging current ideas concerning phylogeny and evolution, as well as the determinants of protein stability. Considering known protein structures from extremophiles, it becomes clear that no general conclusions can be drawn regarding adaptive mechanisms to extremes of physical conditions. Proteins are individuals that accumulate increments of stabilization; in thermophiles these come from charge clusters, networks of hydrogen bonds, optimization of packing and hydrophobic interactions, each in its own way. Recent examples indicate ways for the rational design of ultrastable proteins.
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Proteínas/química , Archaea/genética , Genoma Bacteriano , Cinética , Filogenia , Pliegue de Proteína , TermodinámicaRESUMEN
Gene delivery has shown potential in a variety of applications, including basic research, therapies for inborn genetic defects, cancer, AIDS, tissue engineering, and vaccination. Most available systems have serious drawbacks, such as safety hazards, inefficiency under in vivo-like conditions, and expensive production. When using naked DNA, for instance, a large amount of ultrapure DNA has to be applied as a result of degradation by nucleases. Similarly, the use of eukaryotic histones, synthetic peptides, or peptide nucleic acids may be limited by high production costs. We have demonstrated a biotechnologically feasible and economical approach for gene delivery using the histone-like protein from the hyperthermostable eubacterium Thermotoga maritima, TmHU as an efficient gene transfer reagent. HU can be easily isolated from recombinant Escherichia coli, is extraordinarily stable, and protects dsDNA from thermal denaturation. This study demonstrates its use as an inexpensive tool for gene delivery.
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Proteínas Bacterianas/química , Proteínas de Unión al ADN/genética , Técnicas de Transferencia de Gen , Transfección/métodos , Células 3T3 , Animales , Línea Celular , Proteínas de Unión al ADN/química , Relación Dosis-Respuesta a Droga , Células Eucariotas , Femenino , Galactósidos/metabolismo , Histonas/química , Humanos , Indoles/metabolismo , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/metabolismo , Temperatura , Thermotoga maritima/química , Factores de TiempoRESUMEN
An outbreak of acute gastroenteritis occurred in September 2006 in a boarding school in eastern Austria. Of 113 cases, 101 were hospitalised. In order to identify the outbreak source, a retrospective cohort study on the group at risk was performed, including 222 pupils and 30 staff members. Food exposure in the canteen of the school was identified as the most relevant common link among the cases in the case series investigation. Although the preliminary microbiological investigation made Norovirus infections possible, an in-depth descriptive epidemiological investigation later pointed to food intoxication rather than a viral infection as the cause of the outbreak. The analytical epidemiological investigation implicated boiled rice and chicken wings served in the canteen as the most likely source of the outbreak. Staphylococcus aureus was identified as the causative agent. Further molecular characterisation revealed that the predominant S. aureus type in this outbreak was a new spa type, t2046. The same spa type was isolated from stool specimens of the majority of the cases investigated, from samples of the incriminated boiled rice, and also from a swab of a palmar skin lesion of one of the healthy kitchen workers, who is therefore the most likely source of contamination. This outbreak underlines again the importance of compliance with the basic guidelines for kitchen hygiene.
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Brotes de Enfermedades/estadística & datos numéricos , Contaminación de Alimentos/estadística & datos numéricos , Enfermedades Transmitidas por los Alimentos/epidemiología , Gastroenteritis/epidemiología , Vigilancia de la Población , Infecciones Estafilocócicas/epidemiología , Enfermedad Aguda , Austria/epidemiología , Enfermedades Transmitidas por los Alimentos/microbiología , Gastroenteritis/microbiología , Humanos , Incidencia , Medición de Riesgo/métodos , Factores de Riesgo , Instituciones Académicas/estadística & datos numéricos , Infecciones Estafilocócicas/microbiologíaRESUMEN
BACKGROUND: Rectovaginal fistula is an extremely distressing condition for the patients. There is still no generally accepted standard surgical treatment strategy. Especially the influence of diversion stoma creation on patients' outcome remains controversial. Thus, the aim of this study was to analyze the influences of diversion stoma on the outcome of patients treated because of rectovaginal fistula with special regard to perioperative complications and recurrence rates. METHODS: Between 2003 and 2013, all patients treated due to rectovaginal fistula in our institutions were retrospectively analyzed. A total of 81 procedures were performed in 62 patients. Procedures were divided into two groups depending on the presence of a diversion stoma or not (diversion stoma, n = 42 vs. no stoma, n = 39). RESULTS: The overall rate of fistula recurrence was 44% without statistical significance in-between the study groups (49 vs. 38%; p = 0.603). Diversion stoma had no influence on complication rates, wound infections or number of operative revisions. Patients treated with diversion stoma had significantly higher ASA-scores (2.6 ± 0.6 vs. 2.1 ± 0.8; p = 0.011), higher rates of malignoma (58 vs. 17%; p = 0.001) and larger sizes of fistula (1.67 ± 0.08 vs. 1.51 ± 0.46 mm; p = 0.012). The in-hospital stay was significantly longer in these patients (30 ± 66 vs. 15 ± 15 days; p = 0.023). CONCLUSIONS: Our data suggest that diversion stoma creation does not influence the outcome of patients with rectovaginal fistula with special regard to rates of fistula recurrence. On the other hand it is mainly used in complex cases of sick patients and larger fistula sizes. Prospective clinical studies need to be conducted to reinforce these findings.
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Fístula Rectovaginal/cirugía , Estomas Quirúrgicos/efectos adversos , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Persona de Mediana Edad , Fístula Rectovaginal/patología , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The histone-like protein TmHU from the hyperthermophilic eubacterium Thermotoga maritima was cloned, expressed to high levels in Escherichia coli, and purified to homogeneity by heat precipitation and cation exchange chromatography. CD spectroscopical studies with secondary structure analysis as well as comparative modeling demonstrate that the dimeric TmHU has a tertiary structure similar to other homologous HU proteins. The Tm of the protein was determined to be 96 degrees C, and thermal unfolding is nearly completely reversible. Surface plasmon resonance measurements for TmHU show that the protein binds to DNA in a highly cooperative manner, with a KD of 73 nM and a Hill coefficient of 7.6 for a 56 bp DNA fragment. It is demonstrated that TmHU is capable to increase the melting point of a synthetic, double-stranded DNA (poly[d(A-T)]) by 47 degrees C, thus suggesting that DNA stabilization may be a major function of this protein in hyperthermophiles. The significant in vitro protection of double-helical DNA may be useful for biotechnological applications.
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Proteínas Bacterianas/química , Proteínas Bacterianas/aislamiento & purificación , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/aislamiento & purificación , Thermotoga maritima/química , Sitio Alostérico , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Dicroismo Circular , Clonación Molecular , ADN/química , ADN/genética , ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dimerización , Escherichia coli/genética , Punto Isoeléctrico , Modelos Moleculares , Datos de Secuencia Molecular , Peso Molecular , Desnaturalización de Ácido Nucleico , Conformación Proteica , Desnaturalización Proteica , Pliegue de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Espectrofotometría Ultravioleta , Temperatura , TermodinámicaRESUMEN
Proteins present unique folding structures whose conformations are determined primarily by their amino acid sequences. At present, there is no algorithm that would correlate the sequences with the structures determined by X-ray analysis or NMR. Comparative modeling of a new protein sequence based on the known structure of a functionally related protein promises to yield model structures that may provide relevant properties of the protein. To analyze the quality of a model structure, a set of correlation functions was derived from calculations on a subset of proteins from the structure database. Twenty-three highly resolved protein structures with resolutions of at least 1.7 A from various protein families were used as the primary database. The purpose of this initial work was to find highly sensitive functions (including statistical error limits for the parameters) that describe properties of "real" proteins. Each correlation described is characterized by the correlation coefficient, the parameters for linear or nonlinear regression (coefficients of the equation), standard deviation and variance, and the confidence limits describing the statistical probability for values to occur within these limits, e.g., the natural variability of the property under examination. In addition, a method was developed for creating reasonably misfolded proteins. The ability of a correlation function to discriminate between the native structure and the misfolded conformations is expressed by the reliability index, which indicates the sensitivity of a correlation function. The term correlation functions thus summarizes a variety of efforts to find a mathematical description for the properties of protein structures, for their correlation, and for their significance.
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Modelos Moleculares , Conformación Proteica , Simulación por Computador , Electroquímica , Enlace de Hidrógeno , Pliegue de Proteína , Programas Informáticos , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
Thermotoga maritima (Tm) expresses a 7 kDa monomeric protein whose 18 N-terminal amino acids show 81% identity to N-terminal sequences of cold shock proteins (Csps) from Bacillus caldolyticus and Bacillus stearothermophilus. There were only trace amounts of the protein in Thermotoga cells grown at 80 degrees C. Therefore, to perform physicochemical experiments, the gene was cloned in Escherichia coli. A DNA probe was produced by PCR from genomic Tm DNA with degenerated primers developed from the known N-terminus of TmCsp and the known C-terminus of CspB from Bacillus subtilis. Southern blot analysis of genomic Tm DNA allowed to produce a partial gene library, which was used as a template for PCRs with gene- and vector-specific primers to identify the complete DNA sequence. As reported for other csp genes, the 5' untranslated region of the mRNA was anomalously long; it contained the putative Shine-Dalgarno sequence. The coding part of the gene contained 198 bp, i.e., 66 amino acids. The sequence showed 61% identity to CspB from B. caldolyticus and high similarity to all other known Csps. Computer-based homology modeling allowed the conclusion that TmCsp represents a beta-barrel similar to CspB from B. subtilis and CspA from E. coli. As indicated by spectroscopic analysis, analytical gel permeation chromatography, and mass spectrometry, overexpression of the recombinant protein yielded authentic TmCsp with a molecular weight of 7,474 Da. This was in agreement with the results of analytical ultracentrifugation confirming the monomeric state of the protein. The temperature-induced equilibrium transition at 87 degrees C exceeds the maximum growth temperature of Tm and represents the maximal Tm-value reported for Csps so far.
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Proteínas Bacterianas/análisis , Thermotoga maritima/química , Dicroismo Circular , Cartilla de ADN , Espectrometría de Masas , Modelos Estadísticos , Estructura Secundaria de Proteína , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Espectrofotometría Ultravioleta , TemperaturaRESUMEN
Creatinase (creatine amidinohydrolase, EC 3.5.3.3) from Pseudomonas putida is a homodimer of 45 kDa subunit molecular mass, the three-dimensional structure of which is known at 1.9 A resolution. Three point mutants, A109V, V355M, and V182I, as well as one double mutant combining A109V and V355M, and the triple mutant with all three replacements, were compared with wild-type creatinase regarding their physical and enzymological properties. High-resolution crystal data for wild-type creatinase and the first two mutants suggest isomorphism at least for these three proteins (R. Huber, pers. comm.). Physicochemical measurements confirm this prediction, showing that the mutations have no effect either on the quaternary structure and gross conformation or the catalytic properties as compared to wild-type creatinase. The replacement of V182 (at the solvent-exposed end of the first helix of the C-terminal domain) does not cause significant differences in comparison with the wild-type enzyme. The other point mutations stabilize the first step in the biphasic denaturation transition without affecting the second one. In sum, the enhanced stability seems to reflect slight improvements in the local packing without creating new well-defined bonds. The increase in hydrophobicity generated by the introduction of additional methyl groups (A109V, V182I) must be compensated by minor readjustments of the global structure. Secondary or quaternary interactions are not affected. In going from single to double and triple mutants, to a first approximation, the increments of stabilization are additive.
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Mutagénesis , Pseudomonas putida/enzimología , Ureohidrolasas/química , Clonación Molecular , Activación Enzimática , Estabilidad de Enzimas , Escherichia coli/genética , Guanidina , Guanidinas/farmacología , Cinética , Sustancias Macromoleculares , Nitrosoguanidinas/farmacología , Desnaturalización Proteica , Termodinámica , Urea/farmacología , Ureohidrolasas/genética , Ureohidrolasas/metabolismoRESUMEN
The associations among daily counts of intrauterine mortality and pollutant concentrations (NO2, SO2, CO, O3, and particulate matter (3/4)10 microm) were investigated for the period ranging from January 1991 to December 1992 in the city of São Paulo, Brazil. We used Poisson regression techniques, adjusted for season and weather. The association between intrauterine mortality and air pollution was strong for NO2 (coefficient = 0.0013/ microg/m3; p<0.01) but lesser for SO2 (coefficient = 0.0005/ microg/m3; p<0.10) and CO (coefficient = 0.0223/ppm; p<0.10). A significant association was observed when an index that combined these three pollutants was considered in the models instead of considering each pollutant individually (p<0.01). These associations exhibited a short time lag, not over 5 days. In addition, some evidence of fetal exposure to air pollution was obtained by disclosing a significant association between the levels of carboxyhemoglobin of blood sampled from the umbilical cord and ambient CO levels in children delivered by nonsmoking pregnant women in the period from May to July 1995. Our results suggest that air pollution in São Paulo may promote adverse health effects on fetuses.
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Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales , Muerte Fetal , Adulto , Brasil/epidemiología , Femenino , Humanos , Embarazo , Población UrbanaRESUMEN
We report the MR and clinical findings of two patients with growth hormone deficiency and posterior pituitary ectopia (PPE). Possible causes of PPE are discussed.
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Enfermedades Óseas/genética , Coristoma/genética , Neurohipófisis , Silla Turca , Adulto , Enfermedades Óseas/diagnóstico , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Silla Turca/patologíaRESUMEN
In the past years, much effort has been put on the development of new methodologies and algorithms for the prediction of protein secondary and tertiary structures from (sequence) data; this is reviewed in detail. New approaches for these predictions such as neural network methods, genetic algorithms, machine learning, and graph theoretical methods are discussed. Secondary structure prediction algorithms were improved mostly by considering families of related proteins; however, for the reliable tertiary structure modeling of proteins, knowledge-based techniques are still preferred. Methods and examples with more or less successful results are described. Also, programs and parameterizations for energy minimisations, molecular dynamics, and electrostatic interactions have been improved, especially with respect to their former limits of applicability. Other topics discussed in this review include the use of traditional and on-line databases, the docking problem and surface properties of biomolecules, packing of protein cores, de novo design and protein engineering, prediction of membrane protein structures, the verification and reliability of model structures, and progress made with currently available software and computer hardware. In summary, the prediction of the structure, function, and other properties of a protein is still possible only within limits, but these limits continue to be moved.
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Conformación Proteica , Fenómenos Químicos , Química Física , Simulación por Computador , Modelos MolecularesRESUMEN
In 8 patients with idiopathic chronic urticaria suction blisters were produced simultaneously on lesional and perilesional skin in the periumbilical area without application of heat. The suction pressure was 250 mm Hg, and thus the blister production lasted from 60--120 min. The blister fluid histamine was determined with a modified autoanalyzer technique developed by Siraganian. In this method the extractionof histamine, the condensation of o-phthaldial-dehyde with histamine and the measurement of the fluorochrome is automated. With the described method it is possible to measure values less than 0.5 ng/ml. Histamine levels in perilesional skin were nearly in the same range as in the periumbilical skin of 10 normal persons. The range of the normal tissue fluid histamine levels was 0--15 ng/ml and they did not differ significantly from the plasma levels. In all 8 patients with chronic urticaria the histamine values were higher in lesional than in perilesional skin. In 1 patient the lesional blister fluid histamine value reached 35.5 ng/ml. Four of the patients showed only low differences (less than 3 ng/ml).