The newborn drug development initiative workshop: Summary proceedings from the neurology group on neonatal seizures.

Background: The neonatal period eclipses all other epochs of the human life span for the highest incidence of seizures. Neonatal seizures are most commonly incited by serious acute illnesses such as hypoxic-ischemic encephalopathy, birth trauma, or infection.

Objective: The goal of this article was to summarize some of the Neurology Group's discussion on neonatal seizures and their treatment with phenobarbital (PB).

Chronic Chlamydia pneumoniae infection may promote coronary artery disease in humans through enhancing secretion of interleukin-4.

Atherosclerosis is an inflammatory response, probably to a range of initiating causes. Chronic infection with Chlamydia pneumoniae (C.pn) has been suggested as one cause, but the nature of the association is controversial, in large part due to lack of an identified mechanism to link infection with the atherosclerotic process in man.

Prolonged electroencephalogram monitoring for seizures and their treatment.

This article reviews the diagnosis of neonatal seizures using routine electroencephalogram (EEG) examinations and long-term EEG monitoring. EEG is considered the gold standard for identifying the presence and quantifying the burden of neonatal seizures. The most common medication used to treat neonatal seizures is phenobarbital, although its efficacy has never been demonstrated by a formal, randomized, placebo-controlled drug trial.

Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block.

The role of cardiocytes in physiologic removal of apoptotic cells and the subsequent effect of surface binding by anti-SSA/Ro and -SSB/La antibodies was addressed. Initial experiments evaluated induction of apoptosis by extrinsic and intrinsic pathways. Nuclear injury and the translocation of SSA/Ro and SSB/La antigens to the fetal cardiocyte plasma membrane were common downstream events of Fas and TNF receptor ligation, requiring caspase activation.

The Illness Management and Recovery program: rationale, development, and preliminary findings.

The Illness Management and Recovery (IMR) program was developed based on a comprehensive review of research on teaching illness self-management strategies to clients with schizophrenia and other severe mental illnesses and "packaged" in a resource kit to facilitate dissemination. Despite growing dissemination of this program, it has not yet been empirically validated. This article describes the development and theoretical underpinnings of the IMR program and presents pilot data from the United States and Australia (N = 24, 88% schizophrenia or schizoaffective) on the effects of individual-based and group-based treatment over the 9-month program and over a 3-month follow-up.

Anti-La/SSB antiidiotypic antibodies in maternal serum: a marker of low risk for neonatal lupus in an offspring.

Objective: The anti-La/SSB response to major B cell epitopes of La/SSB can be blocked by an active idiotypic/antiidiotypic network, which can be identified using synthetic complementary epitopes deduced from the sequence of the major B cell epitopes of the molecule. This study evaluated the role of this network in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies in the development of neonatal lupus syndrome (NLS).

Methods: Sixty-three serum samples collected from anti-Ro/anti-La-positive women during pregnancy or within 6 months after delivery were obtained from the Research Registry for Neonatal Lupus and the PR Interval Dexamethasone Evaluation study.

Summary proceedings from the neurology group on neonatal seizures.

One of the highest risk periods for seizures during the human life span is the first month of life. Most neonatal seizures are triggered by acute illness such as hypoxic-ischemic encephalopathy, stroke, or infection; rarely are they triggered by epilepsy per se. Seizures are the most common and important sign of acute neonatal encephalopathy, are a major risk for death or subsequent neurologic disability, and by themselves may contribute to an adverse neurodevelopmental outcome.

Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence.

Polarized immune response to Helicobacter pylori and induction of chronic inflammation may increase the risk of gastric atrophy and adenocarcinoma. We studied the association of the response of IgG1 and IgG2 antibodies to H. pylori with grade of gastric chronic inflammation and atrophy in a population with a high prevalence of H.

Effect of dopamine on rat diaphragm apoptosis and muscle performance.

The purpose of this study was to determine whether dopamine (DA) decreases diaphragm apoptosis and attenuates the decline in diaphragmatic contractile performance associated with repetitive isometric contraction using an in vitro diaphragm preparation. Strenuous diaphragm contractions produce free radicals and muscle apoptosis. Dopamine is a free radical scavenger and, at higher concentrations, increases muscle contractility by simulating beta2-adrenoreceptors.

Dystrophic neuritic processes in epileptic cortex.

Cortical dysplasia is a frequent finding in cortical resections from children with refractory epilepsy. Diagnostic criteria and a classification scheme for cortical dysplasia has been proposed, though the relationship between specific cortical dysplasia features and their causal relationship with epilepsy is poorly understood. We reviewed 28 surgical resections from children and identified a common and easily recognized feature of cortical dysplasia: maloriented, misshapen and occasionally coarse neurofilament stained process forming a dystrophic neuritic background.

Neurodevelopmental outcome after early repair of a ventricular septal defect with or without aortic arch obstruction.

Objectives: Cross-sectional studies of intermediate-term survivors of infant cardiac surgery have revealed a high frequency of neurodevelopmental disabilities. Few data exist regarding neurodevelopmental outcome of infants undergoing surgical intervention for a ventricular septal defect. The purpose of this study was to evaluate the neurodevelopmental outcome at 1 year of age of children who had surgical repair in infancy of a ventricular septal defect or a ventricular septal defect with aortic arch obstruction.

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

Background: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes.

Objective: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality.

Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection.

Background: Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance.

Aim: To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy.

The relationship of postoperative electrographic seizures to neurodevelopmental outcome at 1 year of age after neonatal and infant cardiac surgery.

Objective: The occurrence of a seizure after the arterial switch operation is associated with a worse long-term neurodevelopmental outcome. The significance of seizures after neonatal and infant repair of other congenital heart defects is not known.

Methods: A recent study at our institution demonstrated seizures documented by 48-hour electroencephalographic monitoring in 20 (11%) of 178 neonates and infants after surgery for complex congenital heart defects, including hypoplastic left heart syndrome or variants.

Exposure and binding of selected immunodominant La/SSB epitopes on human apoptotic cells.

Objective: Opsonization of apoptotic cells by autoantibodies bound to surface membrane-translocated La/SSB antigens may initiate tissue damage in the setting of congenital heart block. By injecting pregnant mice with human anti-La antibodies, we previously demonstrated the formation of IgG-apoptotic cell complexes in the developing mouse fetus; however, the binding of anti-La antibodies to human-specific epitopes could not be addressed. Accordingly, the objective of the current study was to delineate the epitope specificity of human La antibodies that are exposed on the surface of apoptotic cells.

Effect of congenital heart disease on neurodevelopmental outcomes within multiple-gestation births.

Objectives: We sought to assess the effect of congenital heart disease requiring surgical intervention with cardiopulmonary bypass at 6 months of age or less on developmental outcomes and growth at 1 year of age while controlling for socioeconomic status, prematurity, home environment, and parental intelligence.

Methods: We performed within-family comparison of 11 multiple-gestation births in which one child had congenital heart disease. At 1 year of age, the Bayley Scales of Infant Development II were administered, and growth parameters were assessed.

Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures.

Objective: Electroencephalographic seizures have been shown to occur in 5% to 20% of neonates and infants after biventricular repair of a variety of cardiac defects. Occurrence of a seizure is a predictor of adverse long-term neurodevelopmental sequelae. The contemporary incidence of postoperative seizures after repair of cardiac defects such as hypoplastic left heart syndrome and other forms of single ventricle is not known.

Probiotics under the regulatory microscope.

This review examines current knowledge regarding the safety of probiotic bacteria in man. Tighter and more comprehensive standards and regulations will be developed as probiotic therapy moves from a limited number of products used in the food industry, into more defined therapeutic categories and more complex organisms. A new framework considering probiotics as nonspecific promoters of mucosal immunity, defines probiotic characteristics and the clinical circumstances in which it is used.

Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects.

Objective: To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52-kd SSA/Ro (Ro 52).

Methods: Serum from mothers enrolled in the Research Registry for Neonatal Lupus and the observational PR Interval and Dexamethasone Evaluation (PRIDE) study was evaluated for reactivity against peptide aa200-239 of Ro 52 (p200), recently reported to be associated with a higher risk of CHB.

Results: The majority of 156 Ro 52-positive sera tested were reactive with p200 (>3 SD above control), irrespective of the clinical status of the child.

Pressure-support ventilation and diaphragm shortening in the rat model.

Little is known about how pressure-support ventilation affects diaphragm performance because there is no direct measurement of diaphragm function in the clinical setting. An indicator of diaphragm performance or work is the product of diaphragm muscle shortening and intrathoracic pressure during inspiration. We studied the effect of pressure-support ventilation on diaphragm shortening, diaphragm work, and other cardiopulmonary parameters.

Selective reduction of anti-Helicobacter pylori IgG subclass antibody in gastric carcinoma.

Background: Epidemiological studies have demonstrated strong links between Helicobacter pylori infection and gastric adenocarcinoma. Recent studies suggest that cell-mediated immunity influences the outcome of infection, including the development of gastric adenocarcinoma. The T-cell response can be characterized in terms of the secreted cytokine profile, which in turn influences the B-cell response including the balance of IgG subclass antibody.

Autoantibodies against the serotoninergic 5-HT4 receptor and congenital heart block: a reassessment.

The specificity of autoantibodies against the serotoninergic 5-HT4 receptor in congenital heart block has led to conflicting observations. In order to clarify the situation, a collaborative effort was undertaken to discover the reasons for these discrepancies and to reassess the importance of such autoantibodies by making use of the Research Registry for Neonatal Lupus. Sera from 128 patients (101 anti-SSA/Ro52 positive mothers among which 74 have children with congenital heart block (CHB), 9 anti-SSA/Ro52 negative patients of which 1 had a child with heart block and 18 healthy donors) were assessed in a single blind test using an ELISA coated with a 5-HT4 receptor-derived peptide.

Enhanced clearance of Candida albicans from the oral cavities of mice following oral administration of Lactobacillus acidophilus.

Orally administered live Lactobacillus acidophilus was assessed for its capacity to enhance clearance from the oral cavity of DBA/2 mice shown previously to be 'infection prone'. L. acidophilus fed to DBA/2 mice significantly shortened the duration of colonization of the oral cavity compared to controls.