Left bundle branch block (LBBB) complicates the diagnosis of acute myocardial infarction (AMI). The Sgarbossa criteria were developed from GUSTO I to surmount this diagnostic challenge but have not ...been prospectively validated in a large population with presumed AMI. We evaluated their utility in the diagnosis and risk stratification of AMI patients in ASSENT 2 & 3.
Baseline electrocardiograms (ECG) of LBBB patients were scored using Sgarbossa's criteria (0-10) by 2 readers blinded to the CK/CK-MB data and clinical outcomes; 267 (1.2%) patients had LBBB on their baseline ECG.
Among 253 LBBB patients with available peak CK/CK-MB data, 158 (62.5%) had peak CK/CK-MB levels >2× ULN, thereby qualifying for the diagnosis of AMI. A Sgarbossa score of 3 was shown in 48.7% of LBBB patients with elevated CK/CK-MB versus in 12.6% of those without a CK/CK-MB rise (
P < .001). Patients with higher Sgarbossa scores, ie, 3, had a higher mortality compared with those with a score <3, (23.5% vs 7.7% at 30 days
P < .001; and 33.7% vs 20.2% at 1 year,
P < .001, respectively).
Our findings validate the utility of Sgarbossa criteria for diagnosing AMI in the setting of LBBB. These criteria provide a simple and practical diagnostic approach to risk stratify this diagnostically challenging high-risk group and optimize risk-benefit of acute therapy.
Many freely motile microorganisms can perceive and transduce external photic stimuli to the motor apparatus, eventually moving, by means of various behavioural strategies, into environments in which ...the illumination conditions are the most favourable for their life. In different microorganisms, a wide range of chromophores operate as light detectors, each of them set in a special molecular pocket that, in its turn, can be linked to another component of the transduction chain. The diverse photosensors are organized in special (and in many cases dedicated) photoreceptor units or subcellular organelles. The main molecular mechanisms connecting the early event of photon absorption to the formation of the signalling state down to the dark steps of the transduction chain are discussed in a selected number of case examples. The possible importance of an intensive multidisciplinary approach to these problems in an evolutionary perspective is finally briefly outlined.
Molecular interactions between hypericin and α-, β- and γ-crystallin proteins have been studied by means of absorption and steady-state fluorescence spectroscopy, aiming to clarify if and how the ...pigment binds to the proteins and to investigate the effects of visible-light irradiation on these molecular systems. Such a study is a prerequisite for assessing the possibility of using hypericin as a mild antidepressant and/or as a photodynamic agent for the treatment of eye tumors and eye viral and bacterial diseases without side injuries to the lens. We have shown that in dark-kept samples, with increasing α-crystallin concentration, both the fluorescence emission intensity and the ratio of the absorption maxima around 590 and 550 nm of hypericin increase. These effects have been attributed to the monomerization of nonfluorescent hypericin aggregates caused by the binding of the pigment to α-crystallin. The binding constant of hypericin has been evaluated to be of the order of 3.0 (mg/mL)−1, corresponding to a dissociation constant of the order of 0.3 mg/mL. Following irradiation with light of wavelengths over 400 nm, at an irradiance of 20 mW/cm2, both tryptophan and hypericin fluorescence emission intensities decrease. These effects are suggested to be the consequence of a spatial rearrangement of the protein framework which takes place following the α-crystallin photopolymerization sensitized by hypericin itself described in the literature. For the sake of comparison hypericin has been studied also in the presence of βH-, βL- and γ-crystallins at the same concentration.
The interaction of blepharismin (BP) and oxyblepharismin (OxyBP) with bovine alpha-crystallin (BAC) has been studied both by steady-state and femtosecond spectroscopy, with the aim of assessing the ...possible phototoxicity of these compounds toward the eye tissues. We showed that these pigments form with BAC potentially harmful ground-state complexes, the dissociation constants of which have been estimated to be 6 +/- 2 micromol L(-1) for OxyBP and 9 +/- 4 micromol L(-1) for BP. Irradiation with steady-state visible light of solutions of blepharismins in the presence of BAC proved to induce a quenching of both the pigment and the intrinsic protein fluorescences. These effects were tentatively rationalized in terms of structural changes of alpha-crystallin. On the other hand, femtosecond transient absorption spectroscopy was used to check the occurrence of any type I photoactivity of oxyblepharismin bound to alpha-crystallin. The existence of a particular type of fast photoinduced reaction, not observed in former studies with human serum albumin but present in the natural oxyblepharismin-binding protein, could here be evidenced but no specific reaction was observed during the first few nanoseconds after excitation. Partial denaturation of alpha-crystallin was however found to alter the excited-state behaviour of its complex with oxyblepharismin, making it partly resemble that of free oxyblepharismin in solution.
Among chaperone-like functioning proteins, the lens α-crystallins are of particular interest because they are not renewed, and even minor alterations can hurt their function of maintaining the proper ...refractive index and avoiding cataract formation in the lens. Several reports have suggested the occurrence of remarkable structural modifications in lens proteins in the presence of endogenous and exogenous sensitizers upon exposure to light. In particular, it has been shown in vitro that hypericin, the active ingredient of Hypericum, can bind to and, in the presence of light, cause the photopolymerization of α-crystallin. On the basis of these results it has also been suggested that a subsequent significant impairment of the protein function can occur. Using absorption and emission spectroscopic techniques, as well as circular dichroism, we have studied the structural modifications of α-crystallin resulting from its interaction with hypericin after irradiation with visible light. To investigate the chaperone-like function of α-crystallin, the heat-induced aggregation kinetics of another lens protein, βLow-crystallin, was monitored by measuring the apparent absorption due to scattering at 360 nm as a function of time, and no apparent damage to its functional role was observed. Spectroscopic results, on the contrary, show a prominent reduction in both tryptophan and hypericin fluorescence emission intensity after light irradiation, suggesting an alteration in the tryptophan microenvironment and a high degree of packing of the chromophore due to photoinduced modification of the molecular framework. Control experiments on α-crystallin structurally modified by light in the presence of hypericin indicated that the protein still retains its ability to chaperone both lens crystallins and insulin.
Prior research suggests that patients may be entered into clinical trials with different electrocardiographic (ECG) findings than specified by study protocol criteria; the extent and impact of this ...variability in a large-scale trial have not been previously described.
We evaluated the relationship between case report form (CRF) categorization of the admission ECG and a Core Laboratory and subsequent outcome in a retrospective analysis of a trial of patients with acute ischemia and a broad spectrum of ECG changes (the GUSTO-IIb trial).
In 11
037 patients with CRF information and an interpretable ECG, there was agreement in 89.1% of ST-elevation and 81.9% of non–ST-elevation cases. Among patients designated as having no ST elevation on the CRF, 1-year mortality rates were significantly higher in the subgroup of patients with Core Laboratory–determined ST elevation as compared with those where both the CRF and Core Laboratory classification were in agreement (8.8% vs 6.8%,
P = .0093). Among patients designated as having ST elevation by the CRF, 1-year mortality rates were similar in both the subgroup of patients with and without Core Laboratory agreement (7.7% vs 8.2%,
P = .72).
These findings have important implications for clinicians in routine practice because even a simple evaluation (presence or absence of ST elevation) on the admission ECG was often discordant and was associated with adverse clinical outcome.
In spite of a normal pacemaker function, syncope still occurs in some patients with sick sinus syndrome (SSS). Causes often remain unknown. To identify predictors and etiologies of this bothersome ...symptom, we studied 507 patients who received atrial, ventricular, and dual-chamber pacemakers for SSS. During a mean follow-up of 62 +/- 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagal (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias (11.5%), ventricular tachycardia (5%), acute myocardial ischemia (2.5%), and pacemaker/lead malfunction (6.5%). In 13 patients (29.5%), syncope remained unexplained. The only preimplant predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow-up.
(1) syncope in paced patients with SSS has multiple etiologies and may be multifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holter monitoring is not useful to document bradycardiac origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would provide an explanation for recurrent syncope in patients with normal pacemaker function.
Dolichol, the polyisoprenoid lipid found in all eukaryotic cells and suggested to represent a biomarker of aging, is inserted into cell membranes, also in tissues exposed to light such as the skin. A ...general question about its physiological role is whether dolichol may play the role of a natural barrier for the noxious components of solar radiation. In order to clarify this point, we established that dolichol is a component of human sebum and we performed an " in vitro " study of the effects of UV radiation on the spectral properties of dolichol in isopropanol. Our data clearly show that, following UV irradiation, the optical absorption spectrum of dolichol undergoes remarkable modifications below 400 nm: a significant, strongly dose-dependent, increase of the optical density around 320 nm and a minor, very slightly dose-dependent, raise of the absorbance at 250 nm. On the contrary, UV irradiation causes only minor changes in HPLC profiles and the formation of photooxidative products can be considered negligible in our experimental conditions. These results suggest that dolichol can be considered an innate, unusually efficient and promising UV screen for skin protection.
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