5 research outputs found
Maximal γ-globin expression in the compound heterozygous state for –175 <sup>G</sup>γ HPFH and β<sup>0</sup>39 nonsense thalassaemia: a case study
The –175 (T→C) Gγ hereditary persistence of fetal haemoglobin is a very rare promoter mutation occurring in Caucasians as well as in African-Americans. Heterozygotes for this non-deletional HPFH show 20% HbF, mostly of Gγ type. We describe here a healthy Sardinian man who coinherited –175 (T→C) Gγ HPFH with the β-thalassaemia codon 39 nonsense mutation in trans; he showed 64% HbF, 100% of Gγ type. Although the β-globin haplotype pattern (II/II) was indicative of the presence of the AγT allele on both chromosomes, the AγT expression was undetectable by HPLC even in red cell populations separated by age. The proband was, moreover, homozygous for the –4 bp deletion at position -225 to -222 of Aγ promoter which has recently been associated with decreased AγT globin expression. These findings suggest that this maximal overexpression of Gγ-globin probably reflects intensified stimulation of the mutated Gγ promoter in this hitherto undescribed genetic condition
Hb Tigraye [β79(EF3)Asp→His] in a Caucasian family from Sardinia
We describe here the occurrence of the Hb Tigraye, or beta79(EF3)Asp→His, first discovered in a healthy male of Ethiopian descent, in four members of a Sardinian family, two adults and two newborns, providing additional biochemical and molecular data. Sequencing of the beta globin gene showed the presence of the GAC→CAC mutation at the level of codon 79
Fetal hemoglobin expression in compound heterozygotes for -117 (G→A) <sup>A</sup>γ HPFH and β<sup>0</sup>39 nonsense thalassemia
The-117(G→A) Aγ hereditary persistence of fetal hemoglobin (Greek HPFH) and β039-thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and β039-thal to haplotype II. Haplotype II β039-thal chromosome carries the AγT gene which is a useful marker of γ-gene expression. Since the Hb F level in these compound heterozygotes was significantly higher than in 46 -117 HPFH carriers, the Aγt, and Gγ globin level was determined. AγT was underexpressed while Gγ was significantly increased, which suggests that in -117 Aγ HPFH/β039-thal healthy subjects the increase in Hb F production is determined only by the -117 mutated Aγ gene and the adjacent Gγ gene
Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study
Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general
anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use
of neuromuscular blocking agents is associated with postoperative pulmonary complications.
Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in
28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital
procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge
were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination
within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative
pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were
adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and
adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513.
Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular
blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who
had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI
–5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised
without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49;
ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7)
were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex
instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at
a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes.
Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an
increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of
neuromuscular blockade against the increased risk of postoperative pulmonary complications