Predictors of mortality of patients with acute respiratory failure secondary to chronic obstructive pulmonary disease admitted to an intensive care unit: A one year study

Background

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly require hospitalization and admission to intensive care unit (ICU). It is useful to identify patients at the time of admission who are likely to have poor outcome. This study was carried out to define the predictors of mortality in patients with acute exacerbation of COPD and to device a scoring system using the baseline physiological variables for prognosticating these patients.

Methods

Eighty-two patients with acute respiratory failure secondary to COPD admitted to medical ICU over a one-year period were included. Clinical and demographic profile at the time of admission to ICU including APACHE II score and Glasgow coma scale were recorded at the time of admission to ICU. In addition, acid base disorders, renal functions, liver functions and serum albumin, were recorded at the time of presentation. Primary outcome measure was hospital mortality.

Results

Invasive ventilation was required in 69 patients (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138–1.532); p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95 % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the adjusted odds ratio for the two parameters, had an area under the ROC curve of 91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%.

Conclusion

APACHE II score at admission and SA levels with in 24 hrs after admission are independent predictors of mortality for patients with COPD admitted to ICU. The equation derived from these two parameters is useful for predicting outcome of these patients.     

Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids

Human 20alpha-hydroxysteroid dehydrogenase (h20alpha-HSD; AKR1C1) catalyzes the transformation of progesterone (Prog) into 20alpha-hydroxy-progesterone (20alpha-OHProg). Although h20alpha-HSD shares 98% sequence identity with human type 3 3alpha-HSD (h3alpha-HSD3, AKR1C2), these two enzymes differ greatly in their activities. In order to explain these differences, we have solved the crystal structure of h20alpha-HSD in a ternary complex with NADP(+) and 20alpha-OHProg at 1.59A resolution. The steroid is stabilized by numerous hydrophobic interactions and a hydrogen bond between its O20 and the N(epsilon ) atom of His222. This new interaction prevents the formation of a hydrogen bond with the cofactor, as seen in h3alpha-HSD3 ternary complexes. By combining structural, direct mutagenesis and kinetic studies, we found that the H(222)I substitution decreases the K(m) value for the cofactor 95-fold. With these results, we hypothesize that the rotation of the lateral chain of His222 could be a mediating step between the transformation of Prog and the release of the cofactor. Moreover, crystal structure analysis and direct mutagenesis experiments lead us to identify a new residue involved in the binding of Prog. Indeed, the R(304)L substitution leads to a 65-fold decrease in the K(m) value for Prog reduction. We thus propose that Prog is maintained in a new steroid-binding site composed mainly of residues found in the carboxy-terminal region of the protein.     

A cooperative oxygen binding hemoglobin from Mycobacterium tuberculosis. Stabilization of heme ligands by a distal tyrosine residue

The homodimeric hemoglobin (HbN) from Mycobacterium tuberculosis displays an extremely high oxygen binding affinity and cooperativity. Sequence alignment with other hemoglobins suggests that the proximal F8 ligand is histidine, the distal E7 residue is leucine, and the B10 position is occupied by tyrosine. To determine how these heme pocket residues regulate the ligand binding affinities and physiological functions of HbN, we have measured the resonance Raman spectra of the O(2), CO, and OH(-) derivatives of the wild type protein and the B10 Tyr --> Leu and Phe mutants. Taken together these data demonstrate a unique distal environment in which the heme bound ligands strongly interact with the B10 tyrosine residue. The implications of these data on the physiological functions of HbN and another heme-containing protein, cytochrome c oxidase, are considered.     

Elevated temperature and periodic water stress alter growth and quality of common milkweed (<Emphasis Type="Italic">Asclepias syriaca</Emphasis>) and monarch (<Emphasis Type="Italic">Danaus plexippus</Emphasis>) larval performance

In this study, we examined the independent and interactive effects of temperature and water availability on the growth and foliar traits of common milkweed (Asclepias syriaca) and performance of a specialist herbivore, larvae of the monarch butterfly (Danaus plexippus). Milkweed from multiple population sources collected across a latitudinal gradient in Wisconsin, USA, were grown under all combinations of ambient or elevated temperature and the presence or absence of periodic water stress. Elevated temperature marginally increased, while water stress decreased plant growth. Milkweed from more northerly latitudes experienced larger growth responses to elevated temperature and were more resistant to water stress, especially under higher temperatures. Elevated temperature and water stress also altered milkweed composite foliar trait profiles. Elevated temperature generally increased leaf nitrogen and structural compounds, and decreased leaf mass per area. Water stress also elevated foliar nitrogen, but reduced defensive traits. Monarch larvae performed well on milkweed under elevated temperature and water stress, but gained the most mass on plants exposed to both treatments in combination. Our findings suggest that milkweed populations from more northerly latitudes in the upper Midwest may benefit more from rising temperatures than those in southerly locations, but that these beneficial effects depend on water availability. Monarch larvae grew larger on plants from all experimental treatments relative to ambient condition controls, indicating that future changes in milkweed presence on the landscape will likely influence monarch populations more than the effects of future changes in plant quality on larval performance.     

Brood predation pressure during parental care does not influence parental enzyme activities related to swimming activity in a teleost fish

Predation is considered one of the main costs to reproduction but is rarely examined from a physiological perspective. In particular, little is known about the influence of brood predation pressure on the physiology of parents engaged in care. Brood defense, even when there is no direct threat to the parent, can be costly as it requires constant vigilance and chasing predators to protect the developing brood and maintain parental investment (i.e., fitness). Our goal was to examine the influence of natural variation in nest predation pressure on the physiology of the teleost smallmouth bass Micropterus dolomieu, an animal that provides sole-paternal care for developing offspring. More specifically, we used indicators of anaerobic (lactate dehydrogenase [LDH]) and aerobic capacity (cytochrome c oxidase [CCO] and citrate synthase [CS]) in axial white muscle and pectoral red muscle to test for differences in antipredator performance of nest guarding males across six lakes with natural variation in nest predation pressure. Pectoral red muscle enzyme activities and protein concentrations were highly conserved among populations, while axial white muscle showed differences in LDH activities, CCO activities and protein concentrations. However, there was no evidence for higher metabolic capacities in fish from lakes with increased brood predation pressure. Clearly, factors other than predation pressure have a greater influence on white muscle metabolic capacities. Additional research is needed to clarify the extent to which biotic and abiotic factors influence the enzyme activity and organismal performance in wild animals, particularly at the level of the individual and population.     

The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis

The aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis has not been well defined. Here we review two factors which may play a role in the pathogenesis of the disease: genetics and infection. In particular, we discuss the role of autoantibodies to LAMP-2, which may arise following infection with Gram-negative bacteria, and may contribute to the development of ANCA-associated systemic vasculitis in genetically susceptible individuals.     

Interactions between substrates and the haem-bound nitric oxide of ferric and ferrous bacterial nitric oxide synthases

We report here the resonance Raman spectra of the FeIII-NO and FeII-NO complexes of the bacterial NOSs (nitric oxide synthases) from Staphylococcus aureus and Bacillus subtilis. The haem-NO complexes of these bacterial NOSs displayed Fe-N-O frequencies similar to those of the mammalian NOSs, in presence and absence of L-arginine, indicating that haem-bound NO and L-arginine had similar haem environments in bacterial and mammalian NOSs. The only notable difference between the two types of NOS was the lack of change in Fe-N-O frequencies of the FeIII-NO complexes upon (6R) 5,6,7,8-tetrahydro-L-biopterin binding to bacterial NOSs. We report, for the first time, the characterization of NO complexes with NOHA (N(omega)-hydroxy-L-arginine), the substrate used in the second half of the catalytic cycle of NOSs. In the FeIII-NO complexes, both L-arginine and NOHA induced the Fe-N-O bending mode at nearly the same frequency as a result of a steric interaction between the substrates and the haem-bound NO. However, in the FeII-NO complexes, the Fe-N-O bending mode was not observed and the nu(Fe-NO) mode displayed a 5 cm(-1) higher frequency in the complex with NOHA than in the complex with L-arginine as a result of direct interactions that probably involve hydrogen bonds. The different behaviour of the substrates in the FeII-NO complexes thus reveal that the interactions between haem-bound NO and the substrates are finely tuned by the geometry of the Fe-ligand structure and are relevant to the use of the FeII-NO complex as a model of the oxygenated complex of NOSs.     

The Impact of Collagen Fibril Polarity on Second Harmonic Generation Microscopy

In this work, we report the implementation of interferometric second harmonic generation (SHG) microscopy with femtosecond pulses. As a proof of concept, we imaged the phase distribution of SHG signal from the complex collagen architecture of juvenile equine growth cartilage. The results are analyzed in respect to numerical simulations to extract the relative orientation of collagen fibrils within the tissue. Our results reveal large domains of constant phase together with regions of quasi-random phase, which are correlated to respectively high- and low-intensity regions in the standard SHG images. A comparison with polarization-resolved SHG highlights the crucial role of relative fibril polarity in determining the SHG signal intensity. Indeed, it appears that even a well-organized noncentrosymmetric structure emits low SHG signal intensity if it has no predominant local polarity. This work illustrates how the complex architecture of noncentrosymmetric scatterers at the nanoscale governs the coherent building of SHG signal within the focal volume and is a key advance toward a complete understanding of the structural origin of SHG signals from tissues.