[Factors associated with the prognosis of mechanically ventilated infants and children. An international study]. / Factores asociados al pronóstico de los pacientes pediátricos ventilados mecánicamente. Un estudio internacional.

OBJECTIVE: Identify factors associated with the survival of pediatric patients who are submitted to mechanical ventilation (MV) for more than 12 hours. DESIGN: International prospective cohort study. It was performed between April 1 and May 31 1999. All patients were followed-up during 28 days or discharge to pediatric intensive care unit (PICU). SETTING: 36 PICUs from 7 countries. PATIENTS: A total of 659 ventilated patients were enrolled but 15 patients were excluded because their vital status was unknown on discharge. RESULTS: Overall in-UCIP mortality rate was 15,6%. Recursive partitioning and logistic regression were used and an outcome model was constructed. The variables significantly associated with mortality were: peak inspiratory pressure (PIP), acute renal failure (ARF), PRISM score and severe hypoxemia (PaO2/FiO2 < 100). The subgroup with best outcome (mortality 7%) included patients who were ventilated with a PIP < 35 cmH2O, without ARF, or PaO2/FiO2 > 100 and PRISM < 27. In patients with a mean PaO2/FiO2 < 100 during MV mortality increased to 26% (OR: 4.4; 95% CI 2.0 to 9.4). Patients with a PRISM score > 27 on admission to PICU had a mortality of 43% (OR: 9.6; 95% CI 4,2 to 25,8). Development of acute renal failure was associated with a mortality of 50% (OR: 12.7; 95% CI 6.3 to 25.7). Finally, the worst outcome (mortality 58%) was for patients with a mean PIP >/= 35 cmH2O (OR 17.3; 95% CI 8.5 to 36.3). CONCLUSION: In a large cohort of mechanically ventilated pediatric patients we found that severity of illness at admission, high mean PIP, development of acute renal failure and severe hypoxemia over the course of MV were the factors associated with lower survival rate.

The default state of the membrane-localized histidine kinase PrrB of Rhodobacter sphaeroides 2.4.1 is in the kinase-positive mode.

The PrrBA two-component activation system of Rhodobacter sphaeroides plays a major role in the induction of photosynthesis gene expression under oxygen-limiting or anaerobic conditions. The PrrB histidine kinase is composed of two structurally identifiable regions, the conserved C-terminal kinase/phosphatase domain and the N-terminal membrane-spanning domain with six transmembrane helices framing three periplasmic and two cytoplasmic loops. Using a set of PrrB mutants with lesions in the transmembrane domain, we demonstrate that the central portion of the PrrB transmembrane domain including the second periplasmic loop plays an important role in both sensing and signal transduction. Signal transduction via the transmembrane domain is ultimately manifested by controlling the activity of the C-terminal kinase/phosphatase domain. The extent of signal transduction is determined by the ability of the transmembrane domain to sense the strength of the inhibitory signal received from the cbb(3) terminal oxidase (J.-I Oh, and S. Kaplan, EMBO J. 19:4237-4247, 2000). Therefore, the intrinsic ("default") state of PrrB is in the kinase-dominant mode. It is also demonstrated that the extent of prrB gene expression is subject to the negative autoregulation of the PrrBA system.

Correlation between culture medium pH, extracellular proteinase activity, and cell growth of Candida albicans in insoluble stratum corneum-supplemented media.

Candida albicans produces a major extracellular proteinase whose activities are observed only in weakly acidic pH. However, in affected lesions, a variety of pH conditions exist, including neutral pH. To verify the pathological importance of the extracellular proteinase, the correlation between culture medium pH, extracellular proteinase activity, and cell growth of C. albicans was followed for 3 weeks with unbuffered and insoluble stratum corneum-supplemented liquid media. Each medium pH, initially adjusted within a range of pH 3-7 by the addition of sodium hydroxide or hydrochloric acid solution, was acidified, and a subsequent high proteolytic activity and rapid fungal growth were observed. After full fungal growth, neutralization of each medium to pH 7 and reduction of proteinase activity occurred. Results from a glucose addition experiment suggest that acidification of each medium was produced by the acid formation from glucose and neutralization by the exhaustion of glucose and increase of ammonia from denatured stratum corneum. These data suggest that extracellular proteinase from C. albicans could act as a virulence factor under a wide range of pH conditions by the acidification of the environmental pH close to the organism.

Relationship between Candida albicans producing proteinase (CAPP) and its environmental pH--comparison with a case of trichophyton mentagrophytes.

Candida albicans produced a karatinolytic proteinase (KPase) or C. albicans producing proteinase (CAPP), a proposed new term for this enzyme, and Trichophyton mentagrophytes also produced KPase when cultivated in liquid medium containing human stratum corneum (HSC) as the nitrogen source, but were unable to do so when cultivated in sabouraud dextrose broth. Purified KPase from the culture supernatants of C. albicans had a molecular weight of 42,000 and an optimum pH at 4.0. The KPase was found to belong to the carboxyl proteinases group and its activity was strongly inhibited by pepstatin. Both fungi were able to grow by secreting KPase which digested HSC for nutrients. KPase from both fungi had high activity in each optimum pH, such as weakly acidic pH on C. albicans and neutral pH on T. mentagrophytes to adapt their surrounding environment by changing the environmental pH into their own optimum pH.