Aeration properties of a new sleeping surface for infants.

BACKGROUND: Prone sleeping position, use of soft mattresses and head covering by bedclothes are known risk factors for sudden infant death syndrome (SIDS). Rebreathing carbon dioxide (CO(2) ) may be a possible mechanism or a confounding factor of SIDS. OBJECTIVE: To compare the aeration properties of a new concept of infant sleeping surface (Net) to three commercial mattresses advertised to improve aeration and to two standard infant mattresses. DESIGN: Two experiments were performed: (I) A container (head box), filled with 7% CO(2) mixture, was opened to the mattress to allow gas mixture to passively diffuse outside and equilibrate with the surrounding room air. (II) Simulation of normal breathing of an infant, using a unidirectional reciprocal syringe, to determine CO(2) accumulation within the head box. METHODS: CO(2) concentrations in the head box were continuously measured until CO(2) levels fell below 1% or for 5 min (experiment I), or until CO(2) accumulation levels plateaued or for 6 min (experiment II). RESULTS: The Net had a significantly faster rate of CO(2) elimination (88.5 ± 4.6 and 91.9 ± 0.9 sec, Net alone and when covered with a sheet, respectively) compared to 238.3 ± 14.2 sec to 387.8 ± 7.9 sec for the other mattresses (P < 0.001). Only the Net was able to prevent CO(2) accumulation with maximal CO(2) levels (0.56 ± 0.03% and 1.16 ± 0.05%; Net alone and when covered with a sheet, respectively) significantly lower than the range of 4.6-6.3% for the other mattresses (P < 0.001). CONCLUSIONS: The new sleeping surface exhibited significantly better aeration properties in dispersing CO(2) and in preventing its accumulation.

[Hereditary angioedema: new mechanisms and therapeutic options].

Hereditary angioedema (HAE) is a rare genetic disorder, manifested by recurrent bouts of swelling in various tissues. The biochemical basis leading to HAE manifestations is either a quantitative or qualitative deficiency in plasma C1 esterase inhibitor (C1-INH). Its proposed physiological role is regulation of vascular permeability, by inhibiting certain steps in the complement, coagulation and the fibrinolytic pathways. Recent evidence implies that bradykinin, a plasma kinin, is the main mediator of HAE, Leading to vasodilatation and hyperpermeability of small vessels. Bradykinin receptors have been recently identified, Leading to significant progress in our understanding of the physiologic mechanisms leading to edema. HAE is characterized by edema of the extremities, face, tongue, Larynx, genitalia and severe abdominal pains. Edema of the tongue and Larynx are life-threatening, and fataloutcomes have been described. Diagnosis of HAE is frequently missed, due to the rarity, non-specific symptoms and lack of awareness of physicians to the diagnosis and treatment. In this review, the authors describe the mechanisms of HAE and the clinical approach to diagnosis and management, according to accepted international guidelines. Furthermore, new treatment modalities that have recently been developed are presented: novel molecules targeting bradykinin, either by inhibiting its generation from plasma kininogens or by direct inhibition of its specific receptors on blood vessels, replacement therapy with human recombinant C1-INH produced in transgenic rabbits. HAE is a chronic disabling diseasewith serious consequences for the patients and their families, severely affecting the quality of life. Recently, new clinical guidelines were published and treatment centers, specializing in the management of HAE were established. The authors are convinced that the increased awareness of the medical staff, in addition to new data and novel treatments, will reduce the burden of the disease, improve its grim prognosis and enable a better quality of life for HAE patients.

Characterization of two missense variants in the hydroxymethylbilane synthase gene in the Israeli population, which differ in their associations with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis caused by molecular defects in the hydroxymethylbilane synthase (HMBS) gene. In this study, we report two novel missense sequence variations in the HMBS gene, T59I (C176T) and V215M (G643A), in two patients with clinical symptoms compatible with acute attacks of porphyria. However, only the patient who carried V215M presented with full AIP-affirming biochemical evidence. Both variant proteins were expressed in a prokaryotic system and characterized in vitro. Recombinant T59I and V215M had residual activity of 80.6% and 19.4%, respectively, of that of the wild type enzyme. Moreover, changes in K(m), V(max) and thermostability observed in the recombinant V215M suggest a causal relationship between V215M and AIP. The association between the T59I substitution and AIP is less obvious. Based on our investigation, substitution T59I is more likely to be a mutation with a weak effect than a rare form of polymorphism. This study demonstrates that in vitro characterization of missense variations in the HMBS gene can provide valuable information for the interpretation of clinical, biochemical and genetic data, for establishing a diagnosis of AIP. It also highlights the fact that there are still many aspects to be investigated concerning AIP and corroborates the need to report new data that can help to clarify the genotype-phenotype relationship.

Hereditary angioedema: new hopes for an orphan disease.

Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities, new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE--icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.