CONTEXT Ethics consultations increasingly are being used to resolve conflicts
about life-sustaining interventions, but few studies have reported their outcomes. OBJECTIVE To investigate whether ...ethics consultations in the intensive care setting
reduce the use of life-sustaining treatments delivered to patients who ultimately
did not survive to hospital discharge, as well as the reactions to the consultations
of physicians, nurses, and patients/surrogates. DESIGN Prospective, multicenter, randomized controlled trial from November
2000 to December 2002. SETTING Adult intensive care units (ICUs) of 7 US hospitals representing a spectrum
of institutional characteristics. PATIENTS Five hundred fifty-one patients in whom value-related treatment conflicts
arose during the course of treatment. INTERVENTIONS Patients were randomly assigned either to an intervention (ethics consultation
offered) (n = 278) or to usual care (n = 273). MAIN OUTCOME MEASURES The primary outcomes were ICU days and life-sustaining treatments in
those patients who did not survive to hospital discharge. We examined the
same measures in those who did survive to discharge and also compared the
overall mortality rates of the intervention and usual care groups. We also
interviewed physicians and nurses and patients/surrogates about their views
of the ethics consultation. RESULTS The intervention and usual-care groups showed no difference in mortality.
However, ethics consultations were associated with reductions in hospital
(−2.95 days, P = .01) and ICU (−1.44
days, P = .03) days and life-sustaining treatments
(−1.7 days with ventilation, P = .03) in those
patients who ultimately did not survive to discharge. The majority (87%) of
physicians, nurses, and patients/surrogates agreed that ethics consultations
in the ICU were helpful in addressing treatment conflicts. CONCLUSION Ethics consultations were useful in resolving conflicts that may have
inappropriately prolonged nonbeneficial or unwanted treatments in the ICU.
The first two steps in the mammalian lysine-degradation pathway are catalyzed by lysine-ketoglutarate reductase and saccharopine dehydrogenase, respectively, resulting in the conversion of lysine to ...α-aminoadipic semialdehyde. Defects in one or both of these activities result in familial hyperlysinemia, an autosomal recessive condition characterized by hyperlysinemia, lysinuria, and variable saccharopinuria. In yeast, lysine-ketoglutarate reductase and saccharopine dehydrogenase are encoded by the LYS1 and LYS9 genes, respectively, and we searched the available sequence databases for their human homologues. We identified a single cDNA that encoded an apparently bifunctional protein, with the N-terminal half similar to that of yeast LYS1 and with the C-terminal half similar to that of yeast LYS9. This bifunctional protein has previously been referred to as “α-aminoadipic semialdehyde synthase,” and we have tentatively designated this gene “
AASS.” The
AASS cDNA contains an open reading frame of 2,781 bp predicted to encode a 927-amino-acid-long protein. The gene has been sequenced and contains 24 exons scattered over 68 kb and maps to chromosome 7q31.3. Northern blot analysis revealed the presence of several transcripts in all tissues examined, with the highest expression occurring in the liver. We sequenced the genomic DNA from a single patient with hyperlysinemia (JJa). The patient is the product of a consanguineous mating and is homozygous for an out-of-frame 9-bp deletion in exon 15, which results in a premature stop codon at position 534 of the protein. On the basis of these and other results, we propose that AASS catalyzes the first two steps of the major lysine-degradation pathway in human cells and that inactivating mutations in the
AASS gene are a cause of hyperlysinemia.
Glutaric acid (GA) and 3‐hydroxyglutaric acid (3GA) are thought to contribute to the degeneration of the caudate and putamen that is seen in some children with glutaric acidaemia type I, a metabolic ...disorder caused by a glutaryl‐CoA dehydrogenase deficiency. This study assessed the neurotoxicity of GA and 3GA (0–50 mmol/L) compared to quinolinic acid (QUIN) in striatal and cortical cultures. All three acids were neurotoxic in a dose‐dependent manner; however, GA and 3GA were both more toxic than QUIN. The neurotoxic effects of low concentrations of GA or 3GA were additive to QUIN toxicity. A series of hormones and growth factors were tested for protection against GA and 3GA toxicity. Insulin (5–500 μU/ml), basic fibroblast growth factor (bFGF; 10 ng/ml), insulin‐like growth factor (IGF‐1; 50 ng/ml), brain‐derived neurotrophic factor (BDNF; 10 ng/ml), glial‐derived neurotrophic factor (GDNF; 10 ng/ml), and two glutamate antagonists were evaluated in brain cultures to which 7 mmol/L GA or 3GA were added. GA and 3GA neurotoxicities were prevented by bFGF. Attenuation of 3GA‐induced neurotoxicity was seen with insulin (5 μU/ml) and IGF‐1. BDNF and GDNF had no effects on neuronal survival. Glutamate antagonists MK801 (10 μmol/L) and NBQX (10 μmol/L) failed to prevent GA or 3GA neurotoxicity. We conclude that GA and 3GA are neurotoxic in cultures of embryonic rat striatum and cortex. Striatal neurons were rescued from death by bFGF and IGF‐1 but not by glutamate antagonist, suggesting that toxicity in this embryonic system is not necessarily mediated by glutamate receptors.
The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data ...recorded in 1100 live days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.
Ammonia decomposition on Ir(100) has been studied over the pressure range from ultrahigh vacuum to 1.5 Torr and at temperatures ranging from 200 to 800 K. The kinetics of the ammonia decomposition ...reaction was monitored by total pressure change. The apparent activation energy obtained in this study (84 kJ/mol) is in excellent agreement with our previous studies using supported Ir catalysts (Ir/Al2O3 82 kJ/mol). Partial pressure dependence studies of the reaction rate yielded a positive order (0.9±0.1) with respect to ammonia and negative order (−0.7 ±0.1) with respect to hydrogen. Temperature-programmed desorption data from clean and hydrogen co-adsorbed Ir(100) surfaces indicate that ammonia undergoes facile decomposition on both these surfaces. Recombinative desorption of N2 is the rate-determining step with a desorption activation energy of ∼63 kJ/mol. Co-adsorption data also indicate that the observed negative order with respect to hydrogen pressure is due to enhancement of the reverse reaction (NHx + H → NHx+1, x=0–2) in the presence of excess H atoms on the surface.
Cryptic subtelomeric rearrangements are suspected to underlie a substantial portion of terminal chromosomal deletions. We have previously described two children, one with an unbalanced subtelomeric ...rearrangement resulting in deletion of 22q13→qter and duplication of 1qter, and a second with an apparently simple 22q13→qter deletion. We have examined two additional patients with deletions of 22q13→qter. In one of the new patients presented here, clinical findings were suggestive of the 22q13 deletion syndrome and FISH for 22qter was requested. Chromosome studies suggested an abnormality involving the telomere of one 22q (46,XX,?add(22)(q13.3)). FISH using Oncor D22S39 and Vysis ARSA probes confirmed a terminal deletion. A multi-telomere FISH assay showed a signal from 19qter on the deleted chromosome 22. Results were confirmed with 19qtel and 22qtel specific probes. The patient is therefore trisomic for 19qter and monosomic for 22qter. The patient's mother was found to have a translocation (19;22)(q13.42;q13.31). We also re-examined chromosomes from two patients previously diagnosed with 22q deletions who were not known to have a rearrangement using the multi-telomere assay. One of these patients was found to have a derivative chromosome 22 (der(22)t(6;22)(p25;q13)). No evidence of rearrangement was detected in the other patient. Thus we have found the 22q13 deletion to be associated with a translocation in three of four patients. This report illustrates the usefulness of examining patients with hypotonia, severe language delay, and mild facial dysmorphism for this syndrome and suggests that most of these deletions may be unbalanced subtelomeric rearrangements.
Climate Change and the Integrity of Science Sills, Jennifer
Science (American Association for the Advancement of Science),
05/2010, Letnik:
328, Številka:
5979
Journal Article
We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of ...neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.
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