In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic ...injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.
Aims
Fabry disease (FD) is a rare X‐linked genetic disorder caused by α‐galactosidase A (AGALA) deficiency. Whereas ‘classic’ variant has multisystemic manifestation, the more recently described ...‘later‐onset’ variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM).
Methods and results
Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso‐Gb3) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity <1.2 μmol/h/L and in females with either low AGALA activity or lyso‐Gb3 > 3.5 ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1 ± 4.3 mm). The average age was 58.4 ± 14.7 years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later‐onset cardiac FD.
Conclusions
We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non‐selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.
Abstract Background The long-term efficacy and safety of alcohol septal ablation (ASA) has recently been demonstrated. However, there is still debate about the outcome of younger patients who should ...be treated using myectomy, according to American College of Cardiology Foundation/American Heart Association guidelines. The aim of this study was to evaluate the long-term outcome of patients ≤ 50 years of age after ASA for hypertrophic obstructive cardiomyopathy (HOCM). Methods We retrospectively evaluated consecutive, highly symptomatic patients aged ≤ 50 years with HOCM who underwent ASA. Results Institutional databases of 3 cardiovascular centres identified 290 patients with HOCM who underwent ASA; 75 (26%) of them were aged ≤ 50 years at the time of their first ASA. Median duration of follow-up was 5.1 years (range, 0.1-15.4 years). Four patients (5%) died during the study period (438 patient-years; the annual mortality rate was 0.91%; 95% confidence interval CI, 0.25-2.34%; the annual mortality rate combined with the first appropriate implantable cardioverter-defibrillator discharge was 1.43%; 95% CI, 0.52-3.10%). Survival free of all-cause mortality at 1, 5, and 10 years was 97% (95% CI, 89-99%), 94% (95% CI, 84-98%), and 94% (95% CI, 84-98%), respectively. Conclusions Results of this first study focused on HOCM patients aged ≤ 50 years who underwent ASA suggest a low risk of all-cause death or appropriate implantable cardioverter-defibrillator discharge in the long-term follow-up.
BACKGROUNDC-reactive protein (CRP) level is a sensitive marker of inflammation and a probable predictor of cardiovascular risk. The aim of this study was to assess the relationship between the ...presence and the extent of coronary atherosclerosis and CRP level in patients referred for coronary angiography for stable angina pectoris or a pathological exercise test.
PATIENTS AND METHODSA group of 200 patients were prospectively analyzed for the relationship between the presence and extent of coronary atherosclerosis and high-sensitivity CRP. Patients with stable angina pectoris or a pathological exercise test were included.
RESULTSFor the whole group the CRP geometric mean was 2.92 mg/l and the median 3.0 mg/l. There was no difference between groups of patients with different extents of coronary lesions (P = 0.320, one-way analysis of variance). In patients without significant coronary disease the CRP geometric mean was 3.1 (2.28–4.21) mg/l with a variation coefficient of 118.4%; in patients with coronary artery disease the geometric mean was 2.83 (2.34–3.43) mg/l with a variation coefficient of 104.0%. The difference in CRP between both groups was not significant (P = 0.601). There was also no significant difference in CRP levels between groups of patients with and without a history of myocardial infarction (2.65 (2.08–3.36) mg/l and 3.18 (2.54–3.98) mg/l, P = 0.266) respectively. There was no correlation between the classification of angina pectoris and the logarithm of CRP level (P = 0.331). This relationship was not confirmed even in the group of patients with significant coronary artery disease (P = 0.693).
CONCLUSIONSCRP level is not related to the extent or the presence of coronary atherosclerosis assessed by coronary angiography, history of myocardial infarction or class of stable angina pectoris in patients referred for coronary angiography for stable angina pectoris or a pathological exercise test.
BACKGROUNDImplantation of coronary stents after predilatation is a standard approach in the treatment of most coronary lesions. Stenting without predilatation could be a possible alternative way of ...treating a certain subset of patients.
OBJECTIVETo identify a group of patients suitable for this optional method, to evaluate their immediate clinical and angiographic outcomes and to test the feasibility and safety of this new therapeutic concept.
METHODSNinety selected patients with 91 lesions were treated by implantation of coronary stents without predilatation.
RESULTSThe mean duration of this procedure was 12.3 ± 9.1 min and the fluoroscopic time was 3.6 ± 2.9 min. The stenoses before and after this procedure were 77 ± 10 and 5 ± 9%, respectively. Predilatation, postdilatation or implantation of an additional stent was necessary for seven patients. Primary success rate was 92% with an excellent immediate clinical and angiographic outcome. No major complications occurred during direct stenting.
CONCLUSIONDirect stenting is feasible using commercially available stents and could be performed for about 20% of patients for whom coronary intervention is indicated. The proper selection of lesions is of crucial importance. Lesions eligible for direct stenting should be without visible calcifications and on vessels without proximal tortuosity. This procedure proved to be safe and successful in this series of coronary interventions.
Fungal homoserine dehydrogenase (HSD) is required for the biosynthesis of threonine, isoleucine and methionine from aspartic acid, and is a target for antifungal agents. HSD from the yeast
...Saccharomyces cerevisiae was overproduced in
Escherichia coli and 25 mg of soluble dimeric enzyme was purified per liter of cell culture in two steps. HSD efficiently reduces aspartate semialdehyde to homoserine (Hse) using either NADH or NADPH with
k
cat/
K
m in the order of 10
6–7 M
−1 s
−1 at pH 7.5. The rate constant of the reverse direction (Hse oxidation) was also significant at pH 9.0 (
k
cat/
K
m≈10
4–5 M
−1 s
−1) but was minimal at pH 7.5. Chemical modification of HSD with diethyl pyrocarbonate (DEPC) resulted in a loss of activity that could be obviated by the presence of substrates. UV difference spectra revealed an increase in absorbance at 240 nm for DEPC-modified HSD consistent with the modification of two histidines (His) per subunit. Amino acid sequence alignment of HSD illustrated the conservation of two His residues among HSDs. These residues, His79 and His309, were substituted to alanine (Ala) using site directed mutagenesis. HSD H79A had similar steady state kinetics to wild type, while
k
cat/
K
m for HSD H309A decreased by almost two orders of magnitude. The recent determination of the X-ray structure of HSD revealed that His309 is located at the dimer interface B. DeLaBarre, P.R. Thompson, G.D. Wright, A.M. Berghuis, Nat. Struct. Biol. 7 (2000) 238–244. The His309Ala mutant enzyme was found in very high molecular weight complexes rather than the expected dimer by analytical gel filtration chromatography analysis. Thus the invariant His309 plays a structural rather than catalytic role in these enzymes.
A number of synthetic tropolones and hydrophobic S-blocked glutathione analogues were investigated as potential inhibitors of glyoxalase I from Saccharomyces cerevisiae and glyoxalase II from bovine ...liver. Several tropolones containing a free C-2 hydroxy group were found to be potent inhibitors of glyoxalase I, whereas the glutathione conjugates were found to be modest to poor inhibitors of this enzyme. Most tropolones and glutathione conjugates, except 5-p-tolylazotropolone and S-carbobenzoxy-L-glutathione, were found to be poor inhibitors of glyoxalase II. A recent report on an extremely active glyoxalase system from Plasmodium falciparum suggested that several of the more potent inhibitors may have antimalarial properties. A number of these compounds in fact, exhibited antimalarial activity in the low micromolar range. Further studies are required to fully elucidate the mechanism(s) of the antimalarial properties of these compounds.
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