The spontaneous breathing trial is of low predictive value regarding spontaneous breathing ability in subjects with prolonged, unsuccessful weaning.

BACKGROUND: The spontaneous breathing trial (SBT) is a well-established diagnostic test for predicting extubation failure in intubated intensive care unit (ICU) patients. However, the SBT has not been evaluated in a specific cohort of tracheostomized patients in whom weaning is prolonged and ultimately unsuccessful. OBJECTIVE: The aim of the trial was to investigate the relevance of SBT failure criteria in chronic respiratory failure subjects undergoing long-term invasive home mechanical ventilation following tracheostomy and weaning failure. METHODS: Measurement of all established failure criteria including pneumotachygraphical assessment of the rapid shallow breathing index (RSBI) took place during an SBT. The decision to continue spontaneous breathing was based on failure criteria as well as the subjective willingness of the patient. RESULTS: Fifteen subjects with a median age of 58 years (interquartile range [IQR] 44-74) were studied; 10 with COPD, 4 with neuromuscular diseases and 1 with both. Twelve subjects met the SBT failure criteria within 30 min, but one third of these subjects were still able to continue with spontaneous breathing. In contrast, 3 subjects could not be weaned despite the SBT being successful. An increased RSBI was the most frequently observed SBT failure criterion (57% of all SBT). However, the SBT varied substantially in individual subjects who were able to sustain spontaneous breathing, despite having reached the cut-off for SBT failure. CONCLUSION: The SBT was of low predictive value regarding spontaneous breathing ability in chronic respiratory failure subjects with prolonged, unsuccessful weaning.

[Evolving Epidemiology of Home Mechanical Ventilation: A Rapidly Growing Challenge for Patient Care]. / Epidemiologische Entwicklung der außerklinischen Beatmung: Eine rasant zunehmende Herausforderung für die ambulante und stationäre Patientenversorgung.

BACKGROUND: Home mechanical ventilation is dramatically evolving in Germany. Patients with non-invasive and invasive ventilation are increasingly treated at home. In-hospital treatment of these patients is also necessary either for control visits or the management of acute medical problems. However, the development of in-hospital patient care, morbidity and mortality of these patients is unknown. METHODS: All patients with long-term dependence on mechanical ventilation for more than three months requiring hospitalisation between 2006 and 2016 were analysed (data obtained from the Federal Statistical Office of Germany). RESULTS: There was an exponential increase in the number of in-patients with long-term dependence of mechanical ventilation. While 24 845 patients were treated in-hospital in 2006, 86 117 patients were treated in 2016. Correspondingly, mortality decreased from 13.2 % (2006) to 5.7 % (2016). In addition, in 2016 47 % of all patients were treated on the intensive care or high dependency care unit. Overall, patients had been severely ill, as there were plenty of medical and neurological co-morbidities. The most common diagnosis was COPD with 58 % of all cases, followed by several cardiology diagnosis. A high number of patients had an impairment of renal function (24 %), in part requiring dialysis. CONCLUSIONS: The rapid development of home mechanical ventilation substantially impacts on the development of the hospital landscape in Germany. The exponential increase of these care-intensive patients is challenging for the health care system and requires a discussion about its limits.

Saliva urea dipstick test: application in chronic kidney disease.

BACKGROUND: A noninvasive test for determining elevated levels of blood urea nitrogen (BUN) may be useful under circumstances in which there is limited access to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we investigated the diagnostic performance of a semiquantitative SUN dipstick to test for elevated BUN levels in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Patients with CKD Stages 1 to 5D were studied. 50 µl of saliva were transferred onto the SUN test strip (Integrated Biomedical Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by visual comparison of the color of the moistened test pad with 6 calibrated color blocks. Interobserver reproducibility was evaluated by independent observers, masked to urea concentrations of 6 calibrated urea solutions. Correlation between SUN and BUN was quantified by Spearman's rank correlation coefficient (RS), Kappa Statistic was employed to evaluate within-sample reproducibility of duplicates. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of SUN. RESULTS: 68 patients (31 females, 60 ± 14 years; 34 hemodialysis patients, 34 patients CKD Stages 1 - 4) were studied. Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within-sample reproducibility was 90%. SUN and BUN were correlated significantly (RS = 0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN determination (area under the ROC curve: 0.90 (95% CI 0.85 - 0.95)). CONCLUSION: Semiquantitative dipstick measurements of SUN can reliably identify CKD patients with elevated BUN levels.

Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin.

The stable introduction of a functional beta-globin gene in haematopoietic stem cells could be a powerful approach to treat beta-thalassaemia and sickle-cell disease. Genetic approaches aiming to increase normal beta-globin expression in the progeny of autologous haematopoietic stem cells might circumvent the limitations and risks of allogeneic cell transplants. However, low-level expression, position effects and transcriptional silencing hampered the effectiveness of viral transduction of the human beta-globin gene when it was linked to minimal regulatory sequences. Here we show that the use of recombinant lentiviruses enables efficient transfer and faithful integration of the human beta-globin gene together with large segments of its locus control region. In long-term recipients of unselected transduced bone marrow cells, tetramers of two murine alpha-globin and two human betaA-globin molecules account for up to 13% of total haemoglobin in mature red cells of normal mice. In beta-thalassaemic heterozygous mice higher percentages are obtained (17% to 24%), which are sufficient to ameliorate anaemia and red cell morphology. Such levels should be of therapeutic benefit in patients with severe defects in haemoglobin production.

The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites.

Retroviruses are highly susceptible to transcriptional silencing and position effects imparted by chromosomal sequences at their integration site. These phenomena hamper the use of recombinant retroviruses as stable gene delivery vectors. As insulators are able to block promoter-enhancer interactions and reduce position effects in some transgenic animals, we examined the effect of an insulator on the expression and structure of randomly integrated recombinant retroviruses. We used the cHS4 element, an insulator from the chicken beta-like globin gene cluster, which has been shown to reduce position effects in transgenic Drosophila. A large panel of mouse erythroleukemia cells that bear a single copy of integrated recombinant retroviruses was generated without using drug selection. We show that the cHS4 increases the probability that integrated proviruses will express and dramatically decreases the level of de novo methylation of the 5' long terminal repeat. These findings support a primary role of methylation in the silencing of retroviruses and suggest that cHS4 could be useful in gene therapy applications to overcome silencing of retroviral vectors.

A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase.

Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.

Reactive oxygen species, lipid peroxidation and enzymatic defence systems in human spermatozoa.

The reactive oxygen species, hydrogen peroxide (H2O2) and superoxide anion (O2o-), were generated with a xanthine-xanthine oxidase system and their effect on human sperm function was studied. The action of reactive oxygen species on selected human spermatozoa resulted in a decreased capacity for ionophore-induced acrosome reaction, a decrease in sperm motility, an increase in the concentration of lipid hydroperoxides and a loss of membrane polyunsaturated fatty acids. H2O2 was the key intermediate of the deleterious effects exerted by the xanthine and xanthine oxidase. Among these parameters, the acrosome reaction appeared most susceptible to the reactive oxygen species generated by the xanthine-xanthine oxidase system, and was decreased without sperm motility being affected. Treatment with H2O2 was shown to inactivate several enzymatic activities involved in the antioxidant defence of spermatozoa: glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase. H2O2 and O2o- were shown to be involved in the lipid alterations triggered by the xanthine-xanthine oxidase system. Singlet oxygen is proposed to intervene in the lipoperoxidation process. The inefficacy of mannitol in protecting spermatozoa suggests that hydroxyl radicals were not produced in the extracellular medium.

Chemotherapy with high dose ifosfamide/mesna plus cisplatin for the treatment of ovarian cancer: a study of the Grupo de Estudio y Tratamiento Latino-Americano del Cancer.

Twenty-one evaluable patients with FIGO stages II-IV epithelial ovarian cancer, median age 57 (range 47-75 years), were treated with ifosfamide (IF), 3 g/m2 diluted in 500 ml saline solution, 8 hour intravenous (i.v.) infusion on days 1-5; mesna 20% of IF dose, i.v. bolus injection, was given at hours 0 and 4; mesna 40% of IF dose by oral route at hours 8 and 12, days 1-5; plus cisplatin 20 mg/m2 diluted in 500 ml saline solution, 2 hour i.v. infusion, days 1-5. Cycles were repeated every 4 weeks. All patients had metastatic lesions (mesentery, pleura, colon, cervix, abdominal wall, lung, liver, bladder, and nodes). Toxicity ranged from mild to moderate. All patients experienced alopecia, nausea, and vomiting. Neutropenia and anemia ranged from mild to moderate. One patient experienced mild brain confusion and two patients microscopic hematuria. Ten clinically complete responses (47%) and five clinically partial responses (23%) were registered, for an overall 70% objective response. However, after a second look performance in 10 patients with clinically complete response, six of 10 patients showed a pathological complete response and four showed pathological partial response. The median duration of complete response is about 33 months, and median partial response duration is 14 months. Although the numbers are small, these data indicate that combination chemotherapy with high dose ifosfamide/mesna plus cisplatin may be an active treatment for advanced ovarian carcinoma.

Current biotechnological developments in Belgium.

In recent years, actions have been undertaken by the Belgian government to promote process innovation and technical diversification. Research programs are initiated and coordinated by the study committee for biotechnology setup within the Institute for Scientific Research in Industry and Agriculture (IRSIA). As a result of this action, the main areas where biotechnological processes are developed or commercially exploited include plant genetics, protein engineering, hybridoma technology, biopesticides, production by genetic engineering of vaccines and drugs, monoclonal detection of human and animal deseases, process reactors for aerobic and anaerobic wastewater treatment, and genetic modification of yeast and bacteria as a base for biomass and energy. Development research also includes new fermentation technologies principally based on immobilization of microorganisms, reactor design, and optimization of unit operations involved in downstream processing. Food, pharmaceutical, and chemical industries are involved in genetic engineering and biotechnology and each of these sectors is overviewed in this paper.