New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview

Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult‐to‐manage patients characterized by early‐onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta‐analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self‐sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population‐based, birth and patient cohorts show that early‐onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high‐risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high‐risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss‐of‐function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.     

Ventricular dysrhythmias, left ventricular hypertrophy, and sudden death

Left ventricular hypertrophy has been documented to be a powerful risk factor for sudden death, acute myocardial infarction, and other cardiovascular morbidity and mortality. The major determinant of left ventricular mass is the hemodynamic burden. However, the hypertrophic process is modified by demographic parameters (age, sex, race), nutritional parameters (salt intake, alcohol, obesity), and neuroendocrine factors (angiotensin, catecholamines, growth hormones, etc.). Ventricular ectopy and more serious arrhythmias are commonly seen in patients with left ventricular hypertrophy. Specific antihypertensive therapy will reduce left ventricular hypertrophy, although not all antihypertensive drugs are equipotent in this regard. A reduction in left ventricular hypertrophy has been shown to diminish left-ventricular-hypertrophy-associated arrhythmias. However, it remains to be shown that patients with left ventricular hypertrophy and ventricular ectopy are at a higher risk of sudden death than those without ventricular ectopy and that the reduction of left-ventricular-hypertrophy-associated ventricular ectopy indeed confers a clinical benefit that exceeds the one from the reduction in arterial pressure alone.Modified with permission. Messerli FH and Soria F: Left ventricular hypertrophy and ventricular ectopy. In Podrid PJ and Kower PR, eds.Arrhythmia: A Clinical Approach. ¢ Williams & Wilkins, 1994.     

Left bifascicular block and percutaneous mitral valvuloplasty]

In some patients, the inflation of balloons through the mitral orifice during percutaneous mitral valvuloplasties may impair intraventricular conduction. In some cases, this appears to correspond to a block of the anterior and middle network within the left branch of the bundle of His. This left "biblock" is characterized by extreme left axial deviation of AQRS, of about -60 to -70 degrees, with a QS aspect on D2 and D3, RS on V1 and R on V6 with no major prolongation of ventricular activation time. If this hypothesis is correct, it would support the "trifascicular" concept of the left branch of the bundle of His.     

Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase, inhibits endothelial cell proliferation induced by angiogenic factors in vitro and angiogenesis in in vivo models

Cerivastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It inhibits the biosynthesis of cholesterol and its precursors: farnesyl pyrophosphate and geranylgeranyl pyrophosphate (GGPP), which are involved in Ras and RhoA cell signaling, respectively. Statins induce greater protection against vascular risk than that expected by cholesterol reduction. Therefore, cerivastatin could protect plaque against rupture, an important cause of ischemic events. In this study, the effect of cerivastatin was tested on angiogenesis because it participates in plaque progression and plaque destabilization. Cerivastatin inhibits in vitro the microvascular endothelial cell proliferation induced by growth factors, whereas it has no effect on unstimulated cells. This growth arrest occurs at the G(1)/S phase and is related to the increase of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). These effects are reversed by GGPP, suggesting that the inhibitory effect of cerivastatin is related to RhoA inactivation. This mechanism was confirmed by RhoA delocalization from cell membrane to cytoplasm and actin fiber depolymerization, which are also prevented by GGPP. It was also shown that RhoA-dependent inhibition of cell proliferation is mediated by the inhibition of focal adhesion kinase and Akt activations. Moreover, cerivastatin inhibits in vivo angiogenesis in matrigel and chick chorioallantoic membrane models. These results demonstrate the antiangiogenic activity of statins and suggest that it may contribute to their therapeutic benefits in the progression and acute manifestations of atherosclerosis.     

Inversion of the normal interatrial septum convexity in acute myocardial infarction: incidence, clinical relevance and prognostic significance

Inversion of the normal interatrial septum convexity has been described in patients with right atrial pressure or volume overload, but there is no reference to this abnormality in acute myocardial infarction. A group of 576 consecutive patients with acute infarction and serial echocardiographic studies were prospectively evaluated during a mean follow-up period of 406 days. Inverted interatrial septum convexity was found in 30 patients (5.2%); 29 of the 30 presented with inferior infarction with right ventricular involvement (29 [24.4%] of 119) and the remaining presented with cardiac tamponade secondary to heart rupture. The incidence of inverted interatrial septum convexity rapidly decreased, and after 3 months it was present in only five patients. All patients with inverted interatrial septum convexity had a right atrial pressure greater than or equal to pulmonary capillary pressure, a relation found in only 2 of 43 patients with right ventricular involvement and normal septal convexity. In patients with right ventricular infarction, right atrial pressure was higher in the presence of inverted septal convexity (15.9 +/- 4.1 versus 10.5 +/- 4.1 mm Hg, p less than 0.0001) and the incidence of hypotension (10 [34.4%] of 29 versus 15 [17.4%] of 90, p = 0.04) and third degree atrioventricular block (10 [34.4%] of 29 versus 11 [12.2%] of 90, p = 0.006) as well as the mortality rate after 3 months (9 [31%] of 29 versus 11 [12.2%] of 90, p = 0.04) were higher in the presence of inverted convexity than in patients with normal septal convexity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Episodes of increased fibronectin level observed in a patient suffering from recurrent thrombosis related to congenital hypodysfibrinogenaemia (fibrinogen Malmoe)

A study has been conducted in a Swedish patient with severe thrombotic disease and repeated miscarriages related to a hypodysfibrinogenaemia with defective thrombin binding to the abnormal fibrin. The hypodysfibrinogenaemia was found in several members of the family. The patient also had an increased concentration of fibronectin in her plasma at two different occasions. This would appear to be unrelated to the abnormal fibrinogen since a normal concentration of fibronectin has been found in her relatives presenting the same fibrinogen anomaly, and in the patient at two other times. In conclusion, the thrombotic disorder in this patient presenting a congenital hypodysfibrinogenaemia may be explained by the defective thrombin binding to fibrin.