Maureen O. Meade, MD, MSc; Deborah J. Cook, MD, MSc; Gordon H. Guyatt, MD, MSc; Arthur S. Slutsky, MD; Yaseen M. Arabi, MD; D. James Cooper, MD; Andrew R. Davies, MD; Lori E. Hand, RRT, CCRA; Qi Zhou, PhD; Lehana Thabane, PhD; Peggy Austin, CCRA; Stephen Lapinsky, MD; Alan Baxter, MD; James Russell, MD; Yoanna Skrobik, MD; Juan J. Ronco, MD; Thomas E. Stewart, MD; for the Lung Open Ventilation Study Investigators
JAMA. 2008;299(6):637-645.
Context Low-tidal-volume ventilation reduces mortalityin critically ill patients with acute lung injury and acuterespiratory distress syndrome. Instituting additional strategiesto open collapsed lung tissue may further reduce mortality.
Objective To compare an established low-tidal-volume ventilationstrategy with an experimental strategy based on the original"open-lung approach," combining low tidal volume, lung recruitmentmaneuvers, and high positive-end–expiratory pressure.
Design and Setting Randomized controlled trial with concealedallocation and blinded data analysis conducted between August2000 and March 2006 in 30 intensive care units in Canada, Australia,and Saudi Arabia.
Patients Nine hundred eighty-three consecutive patientswith acute lung injury and a ratio of arterial oxygen tensionto inspired oxygen fraction not exceeding 250.
Interventions The control strategy included target tidalvolumes of 6 mL/kg of predicted body weight, plateau airwaypressures not exceeding 30 cm H2O, and conventional levelsof positive end-expiratory pressure (n = 508). Theexperimental strategy included target tidal volumes of 6 mL/kgof predicted body weight, plateau pressures not exceeding 40cm H2O, recruitment maneuvers, and higher positive end-expiratorypressures (n = 475).
Main Outcome Measure All-cause hospital mortality.
Results Eighty-five percent of the 983 study patientsmet criteria for acute respiratory distress syndrome at enrollment.Tidal volumes remained similar in the 2 groups, and mean positiveend-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimentalgroup vs 9.8 (SD, 2.7) cm H2O among controls during the first72 hours (P < .001). All-cause hospital mortalityrates were 36.4% and 40.4%, respectively (relative risk [RR],0.90; 95% confidence interval [CI], 0.77-1.05; P = .19).Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75;P = .33). The experimental group had lower ratesof refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86;P = .01), death with refractory hypoxemia (4.2% vs8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previouslydefined eligible use of rescue therapies (5.1% vs 9.3%; RR,0.61; 95% CI, 0.38-0.99; P = .045).
Conclusions For patients with acute lung injury and acuterespiratory distress syndrome, a multifaceted protocolized ventilationstrategy designed to recruit and open the lung resulted in nosignificant difference in all-cause hospital mortality or barotraumacompared with an established low-tidal-volume protocolized ventilationstrategy. This "open-lung" strategy did appear to improve secondaryend points related to hypoxemia and use of rescue therapies.
Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein 相似文献
The integrity of sperm DNA is crucial for the maintenance of genetic
health. A major source of damage is reactive oxygen species (ROS)
generation; therefore, antioxidants may afford protection to sperm DNA. The
objectives of the study were, first, to measure the effects of antioxidant
supplementation in vitro on endogenous DNA damage in spermatozoa using the
single cell gel electrophoresis (comet) assay and, second, to assess the
effect of antioxidant supplementation given prior to X-ray irradiation on
induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll
centrifugation in the presence of ascorbic acid (300, 600 microM), alpha
tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5,
10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand
breakage was measured using the comet assay. Sperm DNA was protected from
DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60
microM) and urate (400 microM). These antioxidants provided protection from
subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or
ascorbate and alpha tocopherol together induced further DNA damage.
Supplementation in vitro with the antioxidants ascorbate, urate and alpha
tocopherol separately has beneficial effects for sperm DNA integrity.
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Twenty-six patients over the age of 50 years with proven iron deficiency anaemia were identified, investigated and followed up in general practice over a five-year period. The anaemia was symptomatic in 50% of patients but only 20% had symptoms related to the gut. Faecal occult blood testing was positive in five patients only and negative tests occurred in three patients with significant disease, including one caecal carcinoma. All patients agreed to oesophagogastroduodenoscopy (OGD) and fibreoptic sigmoidoscopy carried out on the same occasion. In eight patients, significant abnormalities were found on OGD and in two patients on sigmoidoscopy. Four patients declined barium enema examinations, two of whom had significant OGD abnormalities. Barium enema examination of the other 22 patients showed polyposis of the colon and a caecal carcinoma and initially missed one carcinoma of the caecum which was found subsequently. The likelihood of finding significant disease in iron-deficient patients over 50 years of age is high and should be assumed to be due to blood loss into the gut. Investigation by OGD, sigmoidoscopy and barium enema in the first instance seems warranted and is a condition that can be safely managed by the GP. (Br J Clin Pract 1997; 51(2) : 78-80) 相似文献
The amino acid sequence of guinea pig MSEL-neurophysin has been determined using tryptic peptides derived from the performic acid-oxidized protein and staphylococcal proteinase peptides obtained from the reduced-carboxamidomethylated neur-ophysin. Guinea pig MSEL-neurophysin consists of a 93-residue polypeptide chain that shows 12 substitutions and 2 deletions when compared to bovine MSEL-neurophysin. It displays the highest number of variations among known mammalian MSEL-neurophysins. These variations are mainly found in the C-terminal region (residues 88–93). Moreover guinea pig MSEL-neurophysin, like rat homologous protein, exhibits substitutions in positions 2, 5, 29 and 81 and lacks an arginine in the penultimate position. Comparison between eight mammalian MSEL-neurophysins reveals a highly conserved region (residues 1 to 88) and a hypervariable region (residues 89 to 93/95). On the other hand the eight species examined are endowed with arginine vasopressin except pig, which has a lysine vasopressin. In the vasopressin-MSEL-neurophysin precursor, the hormonal moiety and the MSEL region of neurophysin (residues 1–9) are encoded by a common exon in ox, rat and man; it can be concluded that this exon is evolutionarily conservative in contrast to the one encoding the C-terminal region of MSEL-neurophysin. 相似文献