Impact of oral immunotherapy on quality of life in children with cow milk allergy: a pilot study.

Quality of life is negatively affected in children with food allergy. Oral immunotherapy is an approach to food allergy that leads to patient desensitization by administering gradually increasing amounts of a given food allergen. The aim of this pilot study is to evaluate how oral immunotherapy affects quality of life in children allergic to cow milk proteins. Thirty children (aged 3-12 years) with cow milk allergy were recruited. Their parents were provided with a validated disease specific quality of life questionnaire (the food allergy quality of life questionnaire -- parent form, FAQLQ-PF) before and again 2 months after completing an oral immunotherapy protocol with cow milk. A significant improvement in all the investigated domains -- emotional impact, food anxiety and social and dietary limitations -- was found. The separate analysis of the different age groups demonstrated that the emotional impact and the food-related anxiety improved in children older than 4, while the social domains improved in each age group. In this pilot experience, oral immunotherapy significantly improves quality of life in children with cow milk allergy. The improvement seems particularly evident in children over 4 years old, who are most likely to benefit from the oral immunotherapy approach. Further placebo-controlled studies are needed to confirm these preliminary results.

Pronóstico a largo plazo de la epilepsia ausencia juvenil / Long term prognosis of juvenile absence epilepsy

Introducción: La epilepsia ausencia juvenil (EAJ) es un tipo de epilepsia generalizada idiopática que se caracteriza por la presencia de crisis de ausencia (CA) que comienzan en la adolescencia, con un EEG típico de punta-onda generalizada, y que puede acompañarse de mioclonías y crisis tónico-clónicas generalizadas (CTCG). El pronóstico a largo plazo es incierto. Material y métodos: Seleccionamos de manera retrospectiva todos los pacientes que cumplían los criterios diagnósticos de EAJ de la ILAE 1989, analizamos las variables clínicas, el tratamiento farmacológico, el estar libre de crisis y la posibilidad de retirar el tratamiento. Resultados: Encontramos 21 pacientes, 17 mujeres y 4 varones, el 86% presentó también CTCG y el 14% mioclonías. La edad de inicio de las CA fue de 17 años (rango: 10-44). Cuatro pacientes comenzaron con CA en la edad adulta. El seguimiento medio fue de 25 años (intervalo: 10-43). El 90% recibió tratamiento con valproato y el 62% requirió politerapia. El 43% de los pacientes están actualmente libres de crisis, aunque todos ellos en tratamiento farmacológico. Todos los intentos de retirar la medicación fracasaron, pese a largos períodos sin crisis.Conclusiones: Menos de la mitad de los pacientes con EAJ están libres de crisis. El tratamiento antiepiléptico es necesario durante toda la vida a pesar de largos períodos de remisiones (AU)

Introduction: Juvenile absence epilepsy (JAE) is a generalized form of epilepsy, characterizedby absence seizures (AS) initiated in adolescence, with a typical EEG showing generalized spikewavedischarges. Apart from absences, other seizure types may be observed such as myocloniaand generalized tonic-clonic seizures (GTCS). Its long-term prognosis is uncertain Material and methods: We retrospectively selected all patients who met the 1989 ILAE diagnostic criteria for JAE. We analysed clinical variables, pharmacological treatment, and seizure remission with medical treatment and seizure relapse after stopping medical treatment. Results: We identified 21 patients, 17 women and 4 men, 86% of whom had suffered GTCS and 14% myoclonias. Mean age at AS onset was 17 years old (range 10-44), 4 patients debuted with AS in adulthood. Mean follow up duration was 25 years (range 14-43). Ninety per cent of the patients were treated with valproate and 62% needed polytherapy. Currently 43% have achieved seizure freedom under medical treatment. All attempts to stop treatment failed, in some cases after long periods of seizure remission. Conclusions: Less than fifty per cent of patients with JAE achieve remission, antiepileptictreatment is mandatory during all life, despite having long periods of remission (AU)

Long term prognosis of juvenile absence epilepsy.

INTRODUCTION: Juvenile absence epilepsy (JAE) is a generalized form of epilepsy, characterized by absence seizures (AS) initiated in adolescence, with a typical EEG showing generalized spike-wave discharges. Apart from absences, other seizure types may be observed such as myoclonia and generalized tonic-clonic seizures (GTCS). Its long-term prognosis is uncertain. MATERIAL AND METHODS: We retrospectively selected all patients who met the 1989 ILAE diagnostic criteria for JAE. We analysed clinical variables, pharmacological treatment, and seizure remission with medical treatment and seizure relapse after stopping medical treatment. RESULTS: We identified 21 patients, 17 women and 4 men, 86% of whom had suffered GTCS and 14% myoclonias. Mean age at AS onset was 17 years old (range 10-44), 4 patients debuted with AS in adulthood. Mean follow up duration was 25 years (range 10-43). Ninety per cent of the patients were treated with valproate and 62% needed polytherapy. Currently 43% have achieved seizure freedom under medical treatment. All attempts to stop treatment failed, in some cases after long periods of seizure remission. CONCLUSIONS: Less than fifty per cent of patients with JAE achieve remission, antiepileptic treatment is mandatory during all life, despite having long periods of remission.

Randomised comparison of the efficacy and safety of a novelDES with biodegradable polymer and cobalt-chromium alloy -Inspiron I trial

Aims: The efficacy of a novel drug eluting stents with biodegradable polymer andcobalt-chromium alloy should be tested in the context of randomised trials, evenwhen using drugs known to be effective, such as sirolimus. The objective of thepresent study was to evaluate the safety and efficacy of a novel formulation of asirolimus-eluting stent with biodegradable polymer and cobalt-chromium alloyagainst a stent with the same metallic structure but without polymer coating or drugelution.Methods and results: The INSPIRON-I trial is a multicenter 2-arm randomisedtrial, conducted in 4 Brazilian institutions, which included 58 patients allocated forthe Inspiron sirolimus-eluting stent or the Cronus bare metal stent in a 2:1 ratio.Patients had de novo coronary lesions in native vessels with a diameter between2.5 and 3.5 mm, amenable for treatment with a single stent of 19 mm or less in length. The primary objective was to compare the in-stent late loss at 6 months of the sirolimus-eluting versus the control bare metal stent. Important secondary objectives included the comparison of major adverse cardiac events (MACE) ofdeath, myocardial infarction and target lesion revascularisation at 12 months. The study randomised 58 patients, 39 in the Inspiron group and 19 in the Cronusgroup. The great majority of the patients included had stable angina (76%).Baseline clinical and angiographic characteristics from both groups were similar, and 55.6% of the lesions were B2/C. The angiographic restudy at 6 months showed that percent diameter stenosis was significantly lower in the Inspiron group (15.8% vs. 38.7%, respectively; p=0.03), as well as late lumen loss (0.18 vs. 0.67 mm; p=0.009). Binary restenosis was also lower for Inspiron group, but without statistical difference (p=0.42)...

Prospective study of the burden of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years of age, in Padova, Italy.

BACKGROUND: Data on the burden of rotavirus gastroenteritis in Europe are needed to help understand the potential impact of introducing new rotavirus vaccines. MATERIALS AND METHODS: As part of prospective observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in Public Health and Society Study, REVEAL) conducted in 2004--2005 in seven European countries, we studied, the characteristics of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years in primary care, emergency room and hospital settings (Padova, Italy). RESULTS: A total of 757 children with acute gastroenteritis were included and enzyme-linked immunoabsorbent assay (ELISA) results were available for 725 cases. The overall estimated annual incidence for rotavirus gastroenteritis was 4.7%. Overall, rotavirus gastroenteritis was estimated to account for 43.6% of acute gastroenteritis cases. Among children with acute gastroenteritis (AGE) aged 6-23 months, 61.2% were rotavirus positive. Rotavirus gastroenteritis (RVGE) was responsible for 68.8% of hospitalizations, 61% of emergency consultations, and 33% of primary care consultations. The most prevalent serotype was G9 (84.4%) followed by G1 (11.8%). The relative risk for rotavirus gastroenteritis of being referred to hospital after an initial consultation in primary care was 3.37 (95% CI: 1.77-6.43) and 3.38 (95% CI: 2.28-5.01) for emergency room referral. Children with rotavirus gastroenteritis generally had more severe disease than children with rotavirus-negative gastroenteritis. CONCLUSION: Rotavirus accounts for a significant proportion of acute gastroenteritis cases in children less than 5 years in Italy, many of whom require frequent primary care consultations, or care in emergency room or hospital settings.

Minisatellite and HPRT mutations in V79 and human cells irradiated with gamma rays.

The induction of mutations at the Hprt locus and minisatellite sequences was studied in V79 cells, peripheral blood lymphocytes (PBL) and lymphoblastoid cells (CCRF-CEM) exposed to gamma rays. In V79 cells the Hprt mutant frequency increased with dose at least up to 6.0 Gy, whereas the number of HPRT mutant lymphocytes increased up to 3 Gy. Clones derived from single irradiated cells were screened for mutations at minisatellite sequences by DNA fingerprint analysis. In V79 cells, a dose-response curve for minisatellite alterations was obtained up to 4.5 Gy. In contrast, very few mutations at minisatellite sequences (2/137) were detected among clones isolated from PBL of two donors irradiated with 1-4 Gy. Similar results were observed in lymphoblastoid CCRF-CEM cells irradiated with 2-3 Gy (4 mutants/180 clones), suggesting that in human lymphoid cells minisatellite DNA is more stable than in other mammalian and human cell lines.

Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil.

Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial). The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment.

High versus low-pressure balloon inflation during multilinktrade mark stent implantation: acute and long-term angiographic results.

We compared the impact of low and high-pressure balloon inflation on acute and late angiographic results of Multilink stent. Low-pressure balloon inflation (9.5 +/- 1.9 atm) was used in 43 stents and high pressure (17.1 +/- 1.5 atm) in 44. A larger immediate luminal gain was achieved in stents with high-pressure balloon inflation (1.80 +/- 0.26 vs. 1.47 +/- 0.62; P = 0.002), resulting in a larger mean diameter in this group (2.71 +/- 0.37 vs. 2.48 +/- 0.47; P = 0.017). At follow-up, a larger luminal diameter was achieved in the high pressure group (1.93 +/- 0.72 vs. 1.45 +/- 0.66; P = 0.002) and a trend to a lower rate of angiographic restenosis (15% vs. 38%, P = 0.08).

Biochemical interactions of the neuronal pentraxins. Neuronal pentraxin (NP) receptor binds to taipoxin and taipoxin-associated calcium-binding protein 49 via NP1 and NP2.

Neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and neuronal pentraxin receptor (NPR) are members of a new family of proteins identified through interaction with a presynaptic snake venom toxin taipoxin. We have proposed that these three neuronal pentraxins represent a novel neuronal uptake pathway that may function during synapse formation and remodeling. We have investigated the mutual interactions of these proteins by characterizing their enrichment on taipoxin affinity columns; by expressing NP1, NP2, and NPR singly and together in Chinese hamster ovary cells; and by generating mice that fail to express NP1. NP1 and NP2 are secreted, exist as higher order multimers (probably pentamers), and interact with taipoxin and taipoxin-associated calcium-binding protein 49 (TCBP49). NPR is expressed on the cell membrane and does not bind taipoxin or TCBP49 by itself, but it can form heteropentamers with NP1 and NP2 that can be released from cell membranes. This is the first demonstration of heteromultimerization of pentraxins and release of a pentraxin complex by proteolysis. These processes are likely to directly effect the localization and function of neuronal pentraxins in neuronal uptake or synapse formation and remodeling.

Single coronary arteries: two cases with distinct and previously undescribed angiographic patterns.

Single coronary artery is a rare congenital anomaly, sometimes associated with myocardial ischemia. We present the clinical and angiographic features of two symptomatic patients with documented myocardial ischemia and with distinct and previously undescribed patterns of single right coronary arteries. These cases are new variants of the types R-I and R-II-A, in which the most probable mechanisms of ischemia are the insufficient blood supply, due to the long trajectories of the single arteries and the presence of underdeveloped vessels. Also, our second case presented with a fistulae from the LCX to the left ventricle, which is another determinant of myocardial ischemia.

Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding protein 49.

We have identified the first putative integral membrane pentraxin and named it neuronal pentraxin receptor (NPR). NPR is enriched by affinity chromatography on columns of a snake venom toxin, taipoxin, and columns of the taipoxin-binding proteins neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and taipoxin-associated calcium-binding protein 49 (TCBP49). The predominant form of NPR contains an putative NH2-terminal transmembrane domain and all forms of NPR are glycosylated. NPR has 49 and 48% amino acid identity to NP1 and NP2, respectively, and NPR message is expressed in neuronal regions that express NP1 and NP2. We suggest that NPR, NP1, NP2, and TCBP49 are involved in a pathway responsible for the transport of taipoxin into synapses and that this may represent a novel neuronal uptake pathway involved in the clearance of synaptic debris.

Mirror image motifs mediate the interaction of the COOH terminus of multiple synaptotagmins with the neurexins and calmodulin.

I have previously reported that the COOH-terminal 34 amino acids of synaptotagmin 1 are capable of interacting with the presynaptic proteins, the neurexins. Multiple synaptotagmins and a synaptotagmin-like protein, rabphilin 3A, are conserved in this domain, raising the possibility that many different synaptotagmins may interact with neurexins. Here 1 report that the COOH termini of synaptotagmins 1, 2, 4, 5, 6, 7, and 9 and rabphilin 3A are capable of interacting with neurexins. The COOH terminus of rabphilin 3A is still capable or substantial enrichment of neurexins from solubilized brain membranes even though only 11 of 33 residues are identical with the COOH terminus of synaptotagmin 1. Like the purification of neurexins on the COOH terminus of synaptotagmin 1, purification by the COOH terminus of rabphilin 3A is calcium-independent. The conservation between carboxyl termini of these proteins suggests symmetrical motifs are necessary for neurexin binding. These include the sequence Leu-X-His-Trp, followed by 13 amino acids, and the sequence Trp-His-X-Lcu. Deletion of the first motif or substitution of residues in the second of these motifs greatly reduces neurexin enrichment. Interestingly, these same COOH termini yield substantial calcium-dependent enrichment of calmodulin mediated by the first of these sequence motifs. This correlates with the binding of 125I-labeled calmodulin by recombinant pieces of synaptotagmn 1 containing the carboxyl terminus. These data suggest that multiple synaptotagmins may interact with neurexins to mediate docking or regulation of neurotransmitter release and that synaptotagmins may be calcium-regulated via interaction with calmodulin.

Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic structure, and chromosomal localization.

We have previously identified novel members of the pentraxin family (neuronal pentraxin 1 and 2) that are expressed in the nervous system. Neuronal pentraxin 1 (NP1) was identified as a rat protein that may mediate the uptake of synaptic material and the presynaptic snake venom toxin, taipoxin. NP2 was identified as a separate gene discovered by screening for a human homolog for NP1. Here, we report human cDNA and mouse genomic DNA sequences for NP1 (gene symbol NPTX1). Human NP1 and mouse NP1 show 95 and 99% amino acid identity, respectively, with rat NP1 and conserve all potential glycosylation sites. Like rat NP1, human NP1 message is large (6.5 kb) and is exclusively localized to the nervous system. The mouse NP1 gene is 13 kb in length and contains four introns that break the coding sequence of NP1 in the same positions as the introns of the human NP2 gene. The human and mouse NP1 genes are localized to chromosome 17q25.1-q25.2 and chromosome 11e2-e1.3, respectively. These data demonstrate the existence of a separate family of pentraxin proteins that are expressed in the human brain and other tissues and that may play important roles in the uptake of extracellular material.

Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization.

We have previously identified a novel rat neuronal member of the pentraxin family (neuronal pentraxin) that may mediate the uptake of synaptic material and the presynaptic snake venom toxin, taipoxin. Here we report human cDNA and genomic sequences of a second neuronal pentraxin. This pentraxin, which we propose to name neuronal pentraxin II (NPII; gene symbol NPTX2), shows 54% amino acid identity to rat neuronal pentraxin (NPI) with 69% identity over the carboxyl-terminal half of NPI and is 88% identical to a newly identified sperm acrosomal pentraxin p50/apexin. Northern blot analysis reveals that NPII message is present in brain, testis, pancreas, liver, heart, and skeletal muscle, so, unlike NPI, NPII is not exclusively localized to neurons. Like NPI, NPII has potential N-linked glycosylation sites. The human NPII gene is 11 kb in length, contains four introns, and is localized to chromosome 7q21.3-q22.1. These data demonstrate the existence of a family of pentraxin proteins that are expressed in the brain and other tissues and that may play important roles in the uptake of extracellular material.

Novel reticular calcium binding protein is purified on taipoxin columns.

We identified, by affinity chromatography, two putative binding proteins for the presynaptic snake venom toxin taipoxin. We have previously characterized one of these proteins [neuronal pentraxin (NP)] as a neuronally secreted protein with homology to acute-phase proteins. Here we report the identification of the second protein as a 49-kDa lumenal calcium binding protein that we have named taipoxin-associated calcium binding protein 49 (TCBP-49). This protein contains six EF-hand putative calcium binding domains and the carboxyl-terminal sequence His-Asp-Glu-Leu (HDEL), identical to the yeast endoplasmic reticulum retention signal. Message for this protein is present in brain, liver, muscle, heart, kidney, and testis. Antibodies to this protein label reticular organelles of neurons and glia. This localization and the specific enrichment of native and recombinant TCBP-49 on columns of immobilized taipoxin raise the possibility that this protein interacts with internalized taipoxin, perhaps mediating its activation. The availability of pure TCBP-49 will allow direct tests of whether TCBP-49 alters the integrity of the oligomeric structure, phospholipase activity, or toxicity of taipoxin.

Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system.

We have identified, by affinity chromatography, a binding protein for the snake venom toxin taipoxin. The sequence of this 47 kDa protein is unique, is characteristic of a secreted protein, and has homology to the acute phase proteins serum amyloid P protein and C-reactive protein of the pentraxin family. We have named this protein neuronal pentraxin (NP), as Northern analysis and in situ hybridization demonstrate high message levels in neurons of cerebellum, hippocampus, and cerebral cortex. Because NP may be released synaptically and has homology to immune proteins potentially involved in uptake of lipidic, toxic, or other antigenic material, we suggest that NP may be involved in a general uptake of synaptic macromolecules.

Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission.

Cloning and characterization of the Drosophila syntaxin-1A gene, syx-1A, reveal that it is present in several tissues but is predominantly expressed in the nervous system, where it is localized to axons and synapses. We have generated an allelic series of loss-of-function mutations that result in embryonic lethality with associated morphological and secretory defects dependent on the severity of the mutant allele. Electrophysiological recordings from partial loss-of-function mutants indicate absence of endogenous synaptic transmission at the neuromuscular junction and an 80% reduction of evoked transmission. Complete absence of syx-1A causes subtle morphological defects in the peripheral and central nervous systems, affects nonneural secretory events, and entirely abolishes neurotransmitter release. These data demonstrate that syntaxin plays a key role in nonneuronal secretion and is absolutely required for evoked neurotransmission.