The liver in uroporphyria : a biochemical and morphological study

The aim of the work described in this thesis was to examine further the mechanisms involved in the accumulation of uroporphyrins in the liver, i.e., the role of iron and an increased activity of one of the preceding enzymes in the heme biosynthetic pathway, PBG-D, in the porphyrinogenic process in experimental uroporphyria and in PCT. In the previous paragraphs, the proposed role of iron in the development of uroporphyria has been discussed. However, a study on the time-sequence relationship between iron accumulation and uroporphyrin production in the liver has not been performed. In addition, the nature of the iron pool involved in this process has not been established. The role of iron in uroporphyria has been explained by its ability to participate in peroxidative and free radical reactions. Desferrioxamine, an iron chelator, has been described to diminish uroporphyrin accumulation in the liver. At present, the specific effects of desferrioxamine on iron accumulation, free radical-mediated reactions, uroporphyrin accumulation and URO-D activity in the liver have not been studied in experimental uroporphyria. It has been reported that the activity of the enzyme PBG-D is increased in erythrocytes and livers of patients with PCT. It is not clear whether this increased PBG-D activity can be observed both in animals with experimental uroporphyria and in humans with sporadic and familial forms of PCT. An increased PBG-D activity could explain the absence of acute attacks in PCT. Moreover, an increased PBG-D activity could also provide an additional explanation for uroporphyrin accumulation in experimental and human uroporphyria

Quantum-limited directional amplifiers with optomechanics

Directional amplifiers are an important resource in quantum information processing, as they protect sensitive quantum systems from excess noise. Here, we propose an implementation of phase-preserving and phase-sensitive directional amplifiers for microwave signals in an electromechanical setup comprising two microwave cavities and two mechanical resonators. We show that both can reach their respective quantum limits on added noise. In the reverse direction, they emit thermal noise stemming from the mechanical resonators and we discuss how this noise can be suppressed, a crucial aspect for technological applications. The isolation bandwidth in both is of the order of the mechanical linewidth divided by the amplitude gain. We derive the bandwidth and gain-bandwidth product for both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth product. Our study represents an important step toward flexible, on-chip integrated nonreciprocal amplifiers of microwave signals

Endoscopic resection for residual oesophageal neoplasia after definitive chemoradiotherapy

Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.</p

Endoscopic resection for residual oesophageal neoplasia after definitive chemoradiotherapy

Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.</p

Конкурентоспроможність персоналу: сутність та місце у забезпеченні конкурентоспроможності підприємства

Розглянути різноманітні точки зору щодо конкурентоспроможності робочої сили та поняття конкурентоспроможності персоналу підприємства. Визначені передумови виникнення поняття конкурентоспроможності персоналу підприємства. Обґрунтовано зв'язок конкурентоспроможності персоналу із конкурентоспроможністю підприємства.Рассмотрены различные точки зрения относительно конкурентоспособности рабочей силы и понятие конкурентоспособности предприятия. Определены предпосылки возникновения понятия конкурентоспособности персонала предприятия. Обоснована связь конкурентоспособности персонала с конкурентоспособностью предприятия.Different points of view are considered in relation to the competitiveness of labour force and concept of competitiveness of enterprise. Pre-conditions of origin of concept of competitiveness of personnel of enterprise are certain. Communication of competitiveness of personnel with the competitiveness of enterprise is grounded

Gastric Acid Suppressive Therapy and Community-Acquired Pneumonia, Etiology and Outcome

Background: Community acquired pneumonia (CAP) is an infection of the pulmonary parenchyma that can be caused by various microbial pathogens. Co-morbidity and medication are related to specific pathogens. Patients on gastric acid suppressive therapy have an increased risk to develop CAP. We aimed to assess whether there are specific pathogens independently associated with gastric acid suppressive therapy and its impact on infection severity. Methods: From December 2007 to January 2010, all subjects consulting the emergency care unit of a general hospital in the south of the Netherlands with a suspected CAP were prospectively registered. Each patient underwent chest radiography. Sputum, urine, nose swabs and blood samples were obtained for microbial culture, antigen detection and polymerase chain reaction techniques, respectively. To study the severity of CAP upon presentation, the validated CURB-65 score was calculated. Furthermore, we assessed hospital or intensive care admission, length of hospitalization and in-hospital mortality. We evaluated the association between use of acid suppressive therapy and microbial aetiology of CAP and severity of illness with logistic regression analysis. Results: The final cohort comprised 463 patients with CAP, defined as presence of infiltrate on chest radiography and/ or microbial aetiology. Overall 136 patients (29%) used acid suppressive therapy, mainly proton pump inhibitors (97%). Patients with acid suppressive therapy more frequently had an infection with Streptococcus pneumoniae (28% vs. 14%) and Haemophilus influenzae (10% vs. 6%), and less frequently with Coxiella burnetii (8% vs. 19%) or H1N1 influenza A virus (2% vs. 7%) in comparison to those without acid suppressive therapy. After adjustment for baseline differences, the risk of proton pump inhibitor users being infected with S. pneumonia was 2.18 times (95%Confidence Interval(CI): 1.2-3.6) higher compared to those not on acid suppressive therapy. Patients using more than one defined daily dose of a PPI had a 1.48-fold increased risk of a S. pneumoniae infection compared with patients using the defined daily dose (95%CI:1.1-2.0). No risk between PPI use and any other microbial pathogen was found. Patients with acid suppressive therapy had on average higher CURB-65 scores, longer hospital stay and subsequently a case fatality rate of 11% vs. 4% compared to those not using acid suppressive therapy. Conclusions. Proton pump inhibitor therapy predisposes with community acquired S. pneumoniae pneumonia, and was associated with higher morbidity