Incidence of hypo- and hyper-capnia in a cross-sectional European cohort of ventilated newborn infants

OBJECTIVE To determine the incidence of hypo- and hyper-capnia in a European cohort of ventilated newborn infants. DESIGN AND SETTING Two-point cross-sectional prospective study in 173 European neonatal intensive care units. PATIENTS AND METHODS Patient characteristics, ventilator settings and measurements, and blood gas analyses were collected for endotracheally ventilated newborn infants on two separate dates. RESULTS A total of 1569 blood gas analyses were performed in 508 included patients with a mean±SD Pco2 of 48±12 mm Hg or 6.4±1.6 kPa (range 17-104 mm Hg or 2.3-13.9 kPa). Hypocapnia (Pco2<30 mm Hg or 4 kPa) and hypercapnia (Pco2>52 mm Hg or 7 kPa) was present in, respectively, 69 (4%) and 492 (31%) of the blood gases. Hypocapnia was most common in the first 3 days of life (7.3%) and hypercapnia after the first week of life (42.6%). Pco2 was significantly higher in preterm infants (49 mm Hg or 6.5 kPa) than term infants (43 mm Hg or 5.7 kPa) and significantly lower during pressure-limited ventilation (47 mm Hg or 6.3±1.6 kPa) compared with volume-targeted ventilation (51 mm Hg or 6.8±1.7 kPa) and high-frequency ventilation (50 mm Hg or 6.7±1.7 kPa). CONCLUSIONS This study shows that hypocapnia is a relatively uncommon finding during neonatal ventilation. The higher incidence of hypercapnia may suggest that permissive hypercapnia has found its way into daily clinical practice.

Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the Nav. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the Nav by shifting the voltage-dependence of steady state activation toward more negative potentials.

Physics potential of a long-baseline neutrino oscillation experiment using a J-PARC neutrino beam and Hyper-Kamiokande

Hyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of HyperKamiokande is the study of CP asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this paper, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis uses the framework and systematic uncertainties derived from the ongoing T2K experiment. With a total exposure of 7.5 MW × 10⁷ s integrated proton beam power (corresponding to 1.56 × 10²² protons on target with a 30 GeV proton beam) to a 2.5-degree off-axis neutrino beam, it is expected that the leptonic CP phase δCP can be determined to better than 19 degrees for all possible values of δCP , and CP violation can be established with a statistical significance of more than 3 σ (5 σ) for 76% (58%) of the δCP parameter space. Using both νe appearance and νµ disappearance data, the expected 1σ uncertainty of sin²θ₂₃ is 0.015(0.006) for sin²θ₂₃ = 0.5(0.45).

[Myocardial dysfunction in sepsis]

Myocardial dysfunction appears in 25% of patients with severe sepsis and in 50% of patients with septic shock, even in the presence of hyper dynamic states. It is characterized by a reduction in left ventricle ejection fraction, that reverts at the seventh to tenth day of evolution. Right ventricular dysfunction and diastolic left ventricular dysfunction can also appear. There is no consensus if an increase in end diastolic volume is part of the syndrome. High troponin or brain natriuretic peptide levels are associated with myocardial dysfunction and a higher mortality. The pathogenesis of myocardial dysfunction is related to micro and macro circulatory changes, inflammatory response, oxidative stress, intracellular calcium management disturbances, metabolic changes, autonomic dysfunction, activation of apoptosis, mitochondrial abnormalities and a derangement in catecholaminergic stimulation. Since there is no specific treatment for myocardial dysfunction, its management requires an adequate multi systemic support to maintain perfusion pressures and systemic flows sufficient for the regional and global demands.

[Management of oxygen delivery and consumption during sepsis]

Maintaining an adequate tissue oxygen delivery (DO(2)) and consumption (VO(2)) is crucial in the treatment of septic patients. A fall in V0(2) is associated with a higher mortality. The early recognition of shock or tissue hypo perfusion impacts on patient prognosis. In occasions, hypovolemia or important regional oxygen debts are not recognized, since macro homodynamic variables have been compensated. In this situation, the use of metabolic hypo perfusion markers such as lactate, central venous oxygen saturation and gastric goniometry, can be helpful. However, interpretation of these markers should be cautious and always considering the overall clinical status of the patient. In the initial stages of sepsis, the dependency of V0(2) on DO(2) predominates as histopathological mechanism of multiple organic failure. In late stages, other factors predominate as determinants of multiple organic failure and mortality, such as hyper or hypo immune response, microcirculatory alterations and cytopathic hypoxia.

Randomized, Double-Blind Trial of the Effect of Fluid Composition on Electrolyte, Acid-Base, and Fluid Homeostasis in Patients Early After Subarachnoid Hemorrhage.

Hyper- and hyponatremia are frequently observed in patients after subarachnoidal hemorrhage, and are potentially related to worse outcome. We hypothesized that the fluid regimen in these patients is associated with distinct changes in serum electrolytes, acid-base disturbances, and fluid balance.

Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families

REASONS FOR PERFORMING STUDY: The horse owner assessed respiratory signs index (HOARSI-1-4, healthy, mildly, moderately and severely affected, respectively) is based on owner-reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in-depth examination of the lower respiratory tract has not been investigated. OBJECTIVES: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI-2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. METHODS: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI-1-4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. RESULTS: HOARSI-3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper-responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. CONCLUSIONS AND CLINICAL RELEVANCE: HOARSI reliably identifies RAO-affected horses in our population.

Isolation of Besnoitia besnoiti from infected cattle in Portugal

Besnoitia besnoiti, an obligate intracellular protozoan parasite belonging to the phylum apicomplexa, is the causative agent of bovine besnoitiosis. Besnoitiosis is responsible for significant losses in the cattle industry of Africa and Mediterranean countries due to the high morbidity rate, abortion and infertility in males. The acute stage of disease is associated with the proliferative forms (tachyzoites) and is characterized by fever, whimpery, general weakness and swelling of the superficial lymph nodes. During the following chronic stage, a huge number of cysts are formed mainly in the subcutaneous tissues. This process is non-reversible, and chronic besnoitiosis is characterized by hyper-sclerodermia, hyperkeratosis, alopecia and, in bulls, atrophy, sclerosis and focal necrosis that cause irreversible lesions in the testis. In this paper we report on the identification of large cysts in the skin of a cow and a bull in Portugal, which presented loss of hair and enlargement and pachydermis all over the body. The observation of a two-layered cyst wall within the host cell, the encapsulation of the host cell by a large outer cyst wall, and the subcutaneous localization of the cysts within the host, were characteristic for B. besnoiti. The parasites were isolated from the infected animals and successfully propagated in Vero cells without prior passages in laboratory animals. Morphological characterization of B. besnoiti tachyzoites and the amplification of the 149 bp segment from the internal transcribed spacer 1 (ITS1), aided with specific primers, confirmed the identification of B. besnoiti.

[Recurrent febrile episodes--normal, periodic fever syndrome or immunodeficiency?]

Fever is one of the main symptoms leading to medical evaluation. Not only infections cause fever but also inflammatory disorders. To distinguish one from another, a thorough medical history and clinical evaluation are needed. Sometimes, only the clinical course will reveal the diagnosis. PFAPA-Syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis) is the most frequent periodic fever syndrome in Switzerland. No diagnostic test is available to support the diagnosis. Some important diseases have to be ruled out, such as Immunodeficiency, cyclic neutropenia, chronic viral infections and rheumatologic disorders. To know the diagnosis of the PFAPA-Syndrome can help avoiding antibiotic courses for febrile episodes in infants. There is a clinical overlap to hereditary periodic fever syndromes as familial Mediterranean fever (FMF), Hyper-IgD and fever syndrome (HIDS), Tumor-necrosis factor receptor associated periodic syndrome (TRAPS) and others, in which a genetic basis for the disease has already been found.

Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole-organ intervertebral disc model

It is generally agreed that the mechanical environment of intervertebral disc cells plays an important role in maintaining a balanced matrix metabolism. The precise mechanism by which the signals are transduced into the cells is poorly understood. Osmotic changes in the extracellular matrix (ECM) are thought to be involved. Current in-vitro studies on this topic are mostly short-term and show conflicting data on the reaction of disc cells subjected to osmotic changes which is partially due to the heterogenous and often substantially-reduced culture systems. The aim of the study was therefore to investigate the effects of cyclic osmotic loading for 4 weeks on metabolism and matrix gene expression in a full-organ intervertebral disc culture system. Intervertebral disc/endplate units were isolated from New Zealand White Rabbits and cultured either in iso-osmotic media (335 mosmol/kg) or were diurnally exposed for 8 hours to hyper-osmotic conditions (485 mosmol/kg). Cell viability, metabolic activity, matrix composition and matrix gene expression profile (collagen types I/II and aggrecan) were monitored using Live/Dead cell viability assay, tetrazolium reduction test (WST 8), proteoglycan and DNA quantification assays and quantitative PCR. The results show that diurnal osmotic stimulation did not have significant effects on proteoglycan content, cellularity and disc cell viability after 28 days in culture. However, hyperosmolarity caused increased cell death in the early culture phase and counteracted up-regulation of type I collagen gene expression in nucleus and annulus cells. Moreover, the initially decreased cellular dehydrogenase activity recovered with osmotic stimulation after 4 weeks and aggrecan gene down-regulation was delayed, although the latter was not significant according to our statistical criteria. In contrast, collagen type II did not respond to the osmotic changes and was down-regulated in both groups. In conclusion, diurnal hyper-osmotic stimulation of a whole-organ disc/endplate culture partially inhibits a matrix gene expression profile as encountered in degenerative disc disease and counteracts cellular metabolic hypo-activity.