Could receptors for advanced glycation end products be considered cardiovascular risk markers in obese children?

Early development of increased cardiovascular risk in obese children and the possible related cardiovascular diseases into adulthood have been shown; however, the underling pathogenetic mechanisms implicated are not yet completely defined. Receptors for advanced glycation end products (RAGE) pathway play a pivotal role in the genesis of abnormality of arterial wall. However, whether obese prepubertal children present impaired levels of endogenous and soluble secretory receptor for advanced glycation end products (esRAGE/sRAGE) and whether an association exists between RAGE levels and carotid intima media thickness (cIMT) are not yet evaluated in this age group. We note that esRAGE and sRAGE were significantly lower in obese children than controls and were independently related to cIMT. Our findings lead to the hypothesis that RAGE system seems to be related to the development of atherosclerosis even in obese prepubertal children.     

Facioscapulohumeral muscular dystrophy and occurrence of heart arrhythmia

BACKGROUND: Subjects with facioscapulohumeral muscular dystrophy (FSHD) do not generally suffer from significant cardiac symptoms. Although with heterogeneous results, studies reported to date indicate that heart alterations unrelated to cardiomyopathy are possible in FSHD. PATIENTS AND METHODS: We describe the findings of a multicenter investigation aimed at detecting cardiac abnormalities in 83 FSHD patients, 44 males and 39 females with a mean age of 47 years. All patients underwent clinical heart examination, 12-lead electrocardiography and 24-hour Holter monitoring; echocardiography was also performed on most patients. RESULTS: Among the 83 patients, 62 with no cardiovascular risk factors were identified. Ten of them manifested clinical or subclinical cardiac involvement: 5 reported symptoms represented mostly by frequent palpitations secondary to supraventricular arrhythmia and another 5 exhibited electrocardiographic signs of short runs of supraventricular paroxysmal tachycardia. In the absence of cardiovascular risk factors, we found symptoms or signs of heart involvement of mainly arrhythmic origin in 10 of our 83 FSHD patients (12%). CONCLUSIONS: Considering our data and those available in the literature as a whole, arrhythmic alterations seem to be detected more frequently than expected in FSHD patients.     

Spatial Distribution of Brainstem Auditory Evoked Potentials and Their Alterations in Lesions of the VIIIth Nerve and Brainstem1

Abstract

Brainstem auditory evoked potentials (brainstem AEPs) were simultaneously recorded from 13 scalp and earlobe electrodes from normal subjects employing a noncephalic reference. The scalp distributions of the individual components (waves I-V) were presented as isopotential maps with the use of a topographic computer display system. Binaural clicks produced symmetrically distributed brainstem AEPs over the scalp. With monaural stimulation, the topography of the responses differed in locus of maximum amplitude for each of the components, suggesting that different generators are involved in the production of these components (for example, wave V is of maximal amplitude with the shortest peak latency over the contralateral frontal area). Wave I was the only component that reversed its polarity according to electrode locations. Other waves were positive over the scalp and earlobes in confonnity with the concept that they are volume conducted, far field potentials. Brainstem AEPs in subjects with lesions in the Vlllth nerve and brainstem have different distributions from those of normal subjects, that is, reversal of polarities of the components after wave I at the ipsilateral earlobe and generalized reduction of their amplitudes over the scalp and contralateral earlobe. Thus an accentuation as well as an attenuation should be carefully evaluated in the clinical assessment of brainstem AEP changes associated with brainstem lesions, for brainstem AEPs are commonly recorded from the vertex referenced to the ipsilateral earlobe. These alterations in the observed field distributions, including polarity reversals of brainstem AEPs, seem to reflect changes in the spatial properties of the generators associated with brainstern lesions, such as a reduction in the magnitude of currents with a possible deviation of the dipole axes assuming that the generator for a given component is approximated by an equivalent dipole layer source.

Brainstem auditory evoked potentials (brainstem AEPs) that can be recorded from the scalp of humans have been considered far field reflections of the potentials generated within the brainstem auditory pathways. In contrast to the long-latency AEPs, it was suggested that the position of the scalp electrode is not critical in determining the waveforms of brainstern AEPs because of the large distance of the electrode from the supposed generators. The concept of far field thus defined by Jewett and Williston (1971) has led many workers to record the potentials only from a single electrode at the vertex with the earlobe or mastoid ipsilateral to stimulation as a reference in clinical applications.

In our laboratory, however, simultaneous bilateral recordings with C₃ to A_l and C₄ to A₂ configurations have been employed. Brainstem AEPs obtained froin both sides were similar in morphology in normal subjects except for wave I, and in lesins of the VIIIth nerve and brainstem considerable asymmetries were recorded. These asymmetries of the brainstem AEPs were correlated with the site of the lesions (Hashimoto et al., 1978; Hashimoto et al., 1979a). Apart from the clinical implications of the asymmetric brainstem AEPs, we think that such profound differences seen at the different locations on the scalp are seemingly inconsistent with the definition of the volume conducted far field potentials.

To our knowledge, there have been few studies involving detailed mapping of the distribution of the potentials in humans (Picton et al., 1974; Streletz et al., 1977; Martin and Moore, 1977). In mapping studies, however, amplitudes and latencies of the brainstem AEP components were measured on separate recordings from various locations on the scalp, presenting the obvious problem of run-to-run variability.

The main objectives of the present study were (1) to map the scalp distribution of each component of brainstem AEPs in normal subjects and patients with VIIIth nerve and brainstem lesions on the basis of simultaneous recordings from multiple electrodes and (2) to relate the altered distributions to the lesions involving various levels of the brainstem. The scalp distributions of the components were presented as isopotential maps with the use of a topographic computer display system (Veno and Matsuoka, 1976).     

The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood

The advanced glycation end products/receptor for advanced glycation end products (AGE–RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = −0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.     

Vasoconstrictor effect of endothelin on the canine coronary artery: is a novel endogenous peptide involved in regulating myocardial blood flow and coronary spasm?

We examined the effect of endothelin on the canine coronary artery (N = 20). The left circumflex coronary artery was cannulated and perfused with arterial blood at constant pressure. Coronary blood flow was monitored by an electromagnetic flowmeter. Intracoronary endothelin provoked a vasoconstriction that was dose-dependent. At a dose of 500 pmol, coronary blood flow was reduced remarkably (91.0 +/- 5.4%, n = 4), and endothelin subsequently produced a fall in systemic blood pressure and ST elevation in the electrocardiogram. At a dose of 100 pmol (n = 9), coronary flow decreased from 16.4 +/- 1.5 ml/min to 12.5 +/- 1.5 ml/min (p less than 0.001) and coronary vascular resistance increased from 6.3 +/- 0.8 mm Hg/ml/min to 9.9 +/- 1.9 mm Hg/ml/min (p less than 0.005). A cumulative dose-response curve to endothelin was obtained and the curves were shifted to the right after both verapamil and nifedipine administration. Therefore endothelin has a potent vasoconstrictor action that is attenuated by the calcium-channel blocker.     

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.