886 resultados para PRELIMINARY CLINICAL-EXPERIENCE
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Bioinformational theory has been proposed by Lang (1979a), who suggests that mental images can be understood as products of the brain's information processing capacity. Imagery involves activation of a network of propositionally coded information stored in long-term memory. Propositions concerning physiological and behavioral responses provide a prototype for overt behavior. Processing of response information is associated with somatovisceral arousal. The theory has implications for imagery rehearsal in sport psychology and can account for a variety of findings in the mental practice literature. Hypotheses drawn from bioinformational theory were tested. College athletes imagined four scenes during which their heart rates were recorded. Subjects tended to show increases in heart rate when imagining scenes with which they had personal experience and which would involve cardiovascular activation if experienced in real life. Nonsignificant heart rate changes were found when the scene involved activation but was one with which subjects did not have personal experience.
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AIM: To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. MATERIAL AND METHODS: Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). RESULTS: Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). CONCLUSION: The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease.
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The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders. Significant advances in genetic technologies and molecular medicine allow huge amounts of information to be generated from individual samples within a reasonable time frame. This review focuses on the role of modifier genes using the example of cystic fibrosis, the most common lethal autosomal recessive disorder in the white population, and discusses the advantages and limitations of candidate gene approaches versus genome-wide association studies. Moreover, the implications of modifier gene research for other monogenic disorders, as well as its significance for diagnostic, prognostic, and therapeutic approaches are summarized. Increasing insight into modifying mechanisms opens up new perspectives, dispelling the idea of genetic disorders being caused by one single gene.
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Human bone is the most direct source for reconstructing health and living conditions of ancient populations. However, many diseases remain undetected in palaeopathology. Möller-Barlow disease (scurvy) is a historically well-documented metabolic disease and must have been common in clinical and sub-clinical severity. Due to long incubation periods and the subtle nature of bone changes osteological evidence is relatively rare (Brickley & Ives 2008). Möller-Barlow disease is caused by deficiency of dietary vitamin C (ascorbic acid) and evokes symptoms like fatigue, haemorrhage, inflammations, delayed wound healing and pain. Vitamin C is a cofactor for the hydroxylation of the amino acids proline and lysine which are essential for the production of intact connective tissue by cross-linking the propeptides in collagen. In a preliminary study we tested the detectability of Möller-Barlow disease by analysis of relative quantitative variability of hydroxylated amino acids in collagen (Pendery & Koon 2013). Samples (N=9) were taken from children with (n=3, cranium, femur, tibia) and without (n=4, cranium, femur, tibia) apparent bone reactions indicative of Möller-Barlow disease, as well as from adults with lethal traumata (n=2; negative controls). The skeletal remains originated from two early medieval cemeteries from Switzerland. Gas chromatographic (GC) analysis revealed minor differences between the samples. So far children with no pathologic alterations had fairly same values as negative controls while children with bone reactions paradoxically exhibited even slightly higher values of hydroxyproline and hydroxylysine. Future research demands for larger sample size and has to discuss sampling strategies. Beside possible misdiagnosis of Möller-Barlow disease it is arguable if only the newly built bone should be analysed even though this could lead to problems related to small sample quantity. It also remains to be seen to which extent varying turnover rates of different skeletal elements, especially in children, must be taken into account.
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The present study tested a theoretically derived link between rumination and depressive symptoms through behavioural avoidance and reduced motive satisfaction as a key aspect of positive reinforcement. Rumination, behavioural avoidance, motive satisfaction and levels of depression were assessed via self-report measures in a clinical sample of 160 patients with major depressive disorder. Path analysis-based mediation analysis was used to estimate the direct and indirect effects as proposed by the theoretical model. Operating in serial, behavioural avoidance and motive satisfaction partially mediated the association between rumination and depressive symptoms, irrespective of gender, medication and co-morbid anxiety disorders. This is the first study investigating the associations between behavioural avoidance, rumination and depression in a clinical sample of depressed patients. The findings are in line with an understanding of rumination in depression as also serving an avoidance function. Copyright © 2014 John Wiley & Sons, Ltd.
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OBJECTIVE To evaluate treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with a new real-time imaging fusion technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection computed tomography (CT) in comparison to conventional post-interventional follow-up. MATERIAL AND METHODS 40 patients with HCC (26 male, ages 46-81 years) were evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was regarded as "successful" treatment, whereas reduction to levels >25% was considered as "partial" treatment response. Homogenous lipiodol retention was regarded as successful treatment in non-enhanced CT. RESULTS Post-interventional image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients (24/40), post-interventional image fusion with CEUS revealed residual tumor vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24 patients. In 16 patients (16/40), post-interventional image fusion with CEUS demonstrated successful treatment, but follow-up CT detected residual viable tumor (6/16). Non-enhanced CT did not identify any case of treatment failure. Image fusion with CEUS assessed treatment efficacy with a specificity of 100%, sensitivity of 80% and a positive predictive value of 1 (negative predictive value 0.63). CONCLUSIONS Image fusion of CEUS with CT allows a reliable, highly specific post-interventional evaluation of embolization response with good sensitivity without any further radiation exposure. It can detect residual viable tumor at early state, resulting in a close patient monitoring or re-therapy.
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Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies. INTRODUCTION: Pre-eclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM) are major sources of clinical morbidity and mortality in pregnant women worldwide. The mechanisms underlying these gestational diseases are complex and not yet fully understood, but one factor contributing to their development is impaired maternal-fetal nutrient transport. Therefore, we aimed to identify candidate membrane transporters involved in transplacental nutrient transfer associated with PE/IUGR or GDM. METHODS: Using in silico strategies, we analysed various gene expression data sets generated on different platforms focusing on solute carriers, ABC transporters and TRP channels in order to identify transporters that are differently expressed between patients and gestational age-matched controls. These bioinformatic analyses were combined with literature data to define a catalogue of target transporters that could be involved in the development of PE/IUGR or GDM. Transporters of interest were then analysed for gene expression using qRT-PCR in placental tissues of patients and controls. For validating the results on protein and functional level, we started to establish an in vitro assay using freshly isolated primary cytotrophoblast cells polarized on the Transwell® system. RESULTS: Using bioinformatics approaches, we initially identified 37 target membrane proteins which were mainly associated with the transport of amino acids, vitamins, and trace elements. At the current state of analysis, the amino acid transporters SLC7A7, SLC38A2, SLC38A5, and the thiamine transporter SLC19A3 showed significant differences in placental mRNA expression between controls and patients affected by PE and/or IUGR. Subsequent gene expression analysis in our in-house GDM placental tissue bank is still ongoing. CONCLUSIONS: Based on our in silico analyses, literature data and first follow-up in vitro validations, we were able to define potentially interesting candidate transporters implicated in PE/IUGR or GDM. To date, additional newly defined candidate targets are being analysed on mRNA level in PE/IUGR and GDM. Subsequent analyses on protein and functional level will reveal whether these targets could be of diagnostic or therapeutical interest in these pregnancy pathologies.
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Periacetabular osteotomy (PAO) is an effective approach for surgical treatment of hip dysplasia. The aim of PAO is to increase acetabular coverage of the femoral head and to reduce contact pressures by reorienting the acetabulum fragment after PAO. The success of PAO significantly depends on the surgeon’s experience. Previously, we have developed a computer-assisted planning and navigation system for PAO, which allows for not only quantifying the 3D hip morphology for a computer-assisted diagnosis of hip dysplasia but also a virtual PAO surgical planning and simulation. In this paper, based on this previously developed PAO planning and navigation system, we developed a 3D finite element (FE) model to investigate the optimal acetabulum reorientation after PAO. Our experimental results showed that an optimal position of the acetabulum can be achieved that maximizes contact area and at the same time minimizes peak contact pressure in pelvic and femoral cartilages. In conclusion, our computer-assisted planning and navigation system with FE modeling can be a promising tool to determine the optimal PAO planning strategy.
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Background Complete-pelvis segmentation in antero-posterior pelvic radiographs is required to create a patient-specific three-dimensional pelvis model for surgical planning and postoperative assessment in image-free navigation of total hip arthroplasty. Methods A fast and robust framework for accurately segmenting the complete pelvis is presented, consisting of two consecutive modules. In the first module, a three-stage method was developed to delineate the left hemipelvis based on statistical appearance and shape models. To handle complex pelvic structures, anatomy-specific information processing techniques were employed. As the input to the second module, the delineated left hemi-pelvis was then reflected about an estimated symmetry line of the radiograph to initialize the right hemi-pelvis segmentation. The right hemi-pelvis was segmented by the same three-stage method, Results Two experiments conducted on respectively 143 and 40 AP radiographs demonstrated a mean segmentation accuracy of 1.61±0.68 mm. A clinical study to investigate the postoperative assessment of acetabular cup orientations based on the proposed framework revealed an average accuracy of 1.2°±0.9° and 1.6°±1.4° for anteversion and inclination, respectively. Delineation of each radiograph costs less than one minute. Conclusions Despite further validation needed, the preliminary results implied the underlying clinical applicability of the proposed framework for image-free THA.
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The overarching objective of this dissertation is to uncover why and how individually experienced fits and misfits translate into different outcomes of user behavior and satisfaction and whether these individual fit/misfit outcomes are in line with organizational intent. In search of patterns and possible archetype users in the context of ES PIPs, this dissertation is the first study that specifically links the theoretical concepts of the aggregated individual fit experiences with the individual and organizational outcome of these experiences (i.e. behavioral reaction, user satisfaction, and alignment with organizational intent). The case study’s findings provide preliminary support for four archetype users characterized by specific fit/misfit experience-outcome patterns.
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BACKGROUND Magnetic resonance imaging (MRI) of the prostate is considered to be the most precise noninvasive staging modality for localized prostate cancer. Multiparametric MRI (mpMRI) dynamic sequences have recently been shown to further increase the accuracy of staging relative to morphological imaging alone. Correct radiological staging, particularly the detection of extraprostatic disease extension, is of paramount importance for target volume definition and dose prescription in highly-conformal curative radiotherapy (RT); in addition, it may affect the risk-adapted duration of additional antihormonal therapy. The purpose of our study was to analyze the impact of mpMRI-based tumor staging in patients undergoing primary RT for prostate cancer. METHODS A total of 122 patients admitted for primary RT for prostate cancer were retrospectively analyzed regarding initial clinical and computed tomography-based staging in comparison with mpMRI staging. Both tumor stage shifts and overall risk group shifts, including prostate-specific antigen (PSA) level and the Gleason score, were assessed. Potential risk factors for upstaging were tested in a multivariate analysis. Finally, the impact of mpMRI-based staging shift on prostate RT and antihormonal therapy was evaluated. RESULTS Overall, tumor stage shift occurred in 55.7% of patients after mpMRI. Upstaging was most prominent in patients showing high-risk serum PSA levels (73%), but was also substantial in patients presenting with low-risk PSA levels (50%) and low-risk Gleason scores (45.2%). Risk group changes occurred in 28.7% of the patients with consequent treatment adaptations regarding target volume delineation and duration of androgen deprivation therapy. High PSA levels were found to be a significant risk factor for tumor upstaging and newly diagnosed seminal vesicle infiltration assessed using mpMRI. CONCLUSIONS Our findings suggest that mpMRI of the prostate leads to substantial tumor upstaging, and can considerably affect treatment decisions in all patient groups undergoing risk-adapted curative RT for prostate cancer.
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BACKGROUND Parameningeal rhabdomyosarcomas (PM-RMSs) represent approximately 25% of all rhabdomyosarcoma (RMS) cases. These tumors are associated with early recurrence and poor prognosis. This study assessed the clinical outcome and late toxicity of pencil beam scanning (PBS) proton therapy (PT) in the treatment of children with PM-RMS. PROCEDURES Thirty-nine children with PM-RMS received neoadjuvant chemotherapy followed by PBS-PT at the Paul Scherrer Institute, with concomitant chemotherapy. The median age was 5.8 years (range, 1.2-16.1). Due to young age, 25 patients (64%) required general anesthesia during PT. The median time from the start of chemotherapy to PT was 13 weeks (range, 3-23 weeks). Median prescription dose was 54 Gy (relative biologic effectiveness, RBE). RESULTS With a mean follow-up of 41 months (range, 9-106 months), 10 patients failed. The actuarial 5-year progression-free survival (PFS) was 72% (95% CI, 67-94%) and the 5-year overall survival was 73% (95% CI, 69-96%). On univariate analysis, a delay in the initiation of PT (>13 weeks) was a significant detrimental factor for PFS. Three (8%) patients presented with grade 3 radiation-induced toxicity. The estimated actuarial 5-year toxicity ≥grade 3 free survival was 95% (95% CI, 94-96%). CONCLUSIONS Our data contribute to the growing body of evidence demonstrating the safety and effectiveness of PT for pediatric patients with PM-RMS. These preliminary results are encouraging and in line with other combined proton-photon and photons series; observed toxicity was acceptable.
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The analgesic effects of peripheral nerve blocks can be prolonged with the placement of perineural catheters allowing repeated injections of local anaesthetics in humans. The objectives of this study were to evaluate the clinical suitability of a perineural coiled catheter (PCC) at the sciatic nerve and to evaluate pain during the early post-operative period in dogs after tibial plateau levelling osteotomy. Pre-operatively, a combined block of the sciatic and the femoral nerves was performed under sonographic guidance (ropivacaine 0.5%; 0.3 mL kg−1 per nerve). Thereafter, a PCC was placed near the sciatic nerve. Carprofen (4 mg kg−1 intravenously) was administered at the end of anaesthesia. After surgery, all dogs were randomly assigned to receive four injections of ropivacaine (group R; 0.25%, 0.3 mL kg−1) or NaCl 0.9% (group C; 0.3 mL kg−1) every 6 h through the PCC. Pain was assessed by use of a visual analogue scale (VAS) and a multi-dimensional pain score (4Avet) before surgery (T-1), for 390 min (T0, T30, T60, T120, T180, T240, T300, T360 and T390) as well as 1 day after surgery (Day 1). Methadone (0.1 mg kg−1) was administered each time the VAS was ≥40 mm or the 4Avet was ≥5. At T390 dogs received buprenorphine (0.02 mg kg−1). Data were compared using Mann–Whitney rank sum tests and repeated measures analysis of variance. Regardless of group allocation, 55% of dogs required methadone. VAS was significantly lower at T390 (P = 0.003), and at Day 1 (P = 0.002) and so was 4Avet at Day 1 (P = 0.012) in group R than in group C. Bleeding occurred in one dog at PCC placement and PCC dislodged six times of 47 PCCs placed. Minor complications occurred with PCC but allowed four repeated administrations of ropivacaine or saline over 24 h in 91.5% of the cases.
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OBJECTIVES The SOURCE XT Registry (Edwards SAPIEN XT Aortic Bioprosthesis Multi-Region Outcome Registry) assessed the use and clinical outcomes with the SAPIEN XT (Edwards Lifesciences, Irvine, California) valve in the real-world setting. BACKGROUND Transcatheter aortic valve replacement is an established treatment for high-risk/inoperable patients with severe aortic stenosis. The SAPIEN XT is a balloon-expandable valve with enhanced features allowing delivery via a lower profile sheath. METHODS The SOURCE XT Registry is a prospective, multicenter, post-approval study. Data from 2,688 patients at 99 sites were analyzed. The main outcome measures were all-cause mortality, stroke, major vascular complications, bleeding, and pacemaker implantations at 30-days and 1 year post-procedure. RESULTS The mean age was 81.4 ± 6.6 years, 42.3% were male, and the mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 20.4 ± 12.4%. Patients had a high burden of coronary disease (44.2%), diabetes (29.4%), renal insufficiency (28.9%), atrial fibrillation (25.6%), and peripheral vascular disease (21.2%). Survival was 93.7% at 30 days and 80.6% at 1 year. At 30-day follow-up, the stroke rate was 3.6%, the rate of major vascular complications was 6.5%, the rate of life-threatening bleeding was 5.5%, the rate of new pacemakers was 9.5%, and the rate of moderate/severe paravalvular leak was 5.5%. Multivariable analysis identified nontransfemoral approach (hazard ratio [HR]: 1.84; p < 0.0001), renal insufficiency (HR: 1.53; p < 0.0001), liver disease (HR: 1.67; p = 0.0453), moderate/severe tricuspid regurgitation (HR: 1.47; p = 0.0019), porcelain aorta (HR: 1.47; p = 0.0352), and atrial fibrillation (HR: 1.41; p = 0.0014), with the highest HRs for 1-year mortality. Major vascular complications and major/life-threatening bleeding were the most frequently seen complications associated with a significant increase in 1-year mortality. CONCLUSIONS The SOURCE XT Registry demonstrated appropriate use of the SAPIEN XT THV in the first year post-commercialization in Europe. The safety profile is sustained, and clinical benefits have been established in the real-world setting. (SOURCE XT Registry; NCT01238497).
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BACKGROUND The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. OBJECTIVES We evaluated the clinical effect of SLNB in patients with thick melanoma. METHODS We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. RESULTS 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). CONCLUSIONS Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.