Neurocognitive functions in pediatric renal transplant patients.

Neurocognitive dysfunction is one of the major complications of chronic renal failure (CRF). Uremic state during CRF encompasses a wide spectrum of neurobehavioral and neurological disturbances. Recent studies showed that the pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels of uremic solutes. Successful renal transplantation improves renal, metabolic, and endocrine functions and the quality of life. The aim of our study was to determine the state of neurocognitive function in pediatric renal transplant recipients. We prospectively performed a neurological examination and neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and Visual and Auditory Number Assay Test) in 20 pediatric renal transplant recipients between 6 and 16 years of age. Twenty healthy children and 20 children with CRF were included in the study as the control groups. Mean age of the renal transplant recipients was 13.50 ± 3.40 years old. Mean evaluation time after transplantation was 2.0 ± 0.5 years. Bender-Gestalt Test result was abnormal in 40% of patients. The results of the Cancellation Test and the Visual and Auditory Number Assay Test showed significant decline in pediatric renal transplant patients when compared with the control. We found that neurocognitive dysfunction was frequent in pediatric renal transplantation patients. Awareness of this potential problem may be helpful for early recognition and treatment. Our findings suggest that periodic neurocognitive assessments may be indicated in transplant recipients.

A comparison between IgE and IgG4 as markers of allergy in children: an experimental trial in a model of natural antigen avoidance.

IgG4 have been hypothesized to act as blocking antibodies capable of preventing IgE-mediated effector cell triggering. This study aims to evaluate the changes in IgG4 in children during a period of natural antigen avoidance. Serum IgE and IgG4 were evaluated in a group of asthmatic children, aged between 7 and 17 years, admitted to the residential house Istituto Pio XII (Misurina, BL, Italy), located at 1,756 m, in a natural model of antigen avoidance. All the patients were skin prick test positive to at least two of the following allergens: Dermatophagoides pteronissynus, Dermatophagoides farinae, cat epithelium, timothy grass pollen and Parietaria pollen. During the 180 days of hospitalization, serum specific IgE and IgG4 were measured six times. A significant decrease (p≤0.05) in serum specific IgE to house dust mite and pollen allergens was observed; by contrast, no significant variations were shown by IgG4 and IgG4/IgE ratio. No significant relationship was found between serum specific IgE, IgG4 and IgG4/IgE ratio variations and the re-exposure to house dust mite allergens during the Christmas holidays. A positive correlation between specific IgE and specific IgG4 was observed at each considered time (T0: r=0.57, p=0.08; T1: r=0.85, p=0.001; T3: r=0.76, p=0.01). The positive correlation between specific IgE and specific IgG4, enduring throughout the entire time of study, suggests a relationship between these classes of immunoglobulins.

Targeting the nasal cavity in rhinitis and sinusitis.

Successful aerosol therapy depends mainly on targeting an adequate dose of drug to the appropriate receptors in the respiratory tract. Over the last years, major innovations have occurred in the delivery of inhaled drugs to the lungs. Despite the fact that more individuals suffer from rhinitis or sinusitis than from asthma or COPD, research into nasal delivery of aerosolized drugs remains scarce. Knowledge of the delivered dose, its regional distribution, and the manner in which drug targeting may be affected by nasal anatomy, air flow and disease condition is very important. Challenges to delivery of aerosolized medications to appropriate targets in the nasal cavity have been scarcely considered. A less-than-optimal technique can result in decreased delivery, reduced efficacy, increased risk of side-effects and high drug wasting. Knowledge of the actual dose and the site of deposition of the delivered drug would permit precise assessment of the relative performance of the delivery systems employed for a specific drug. Optimal physical aerosol characteristics and patient delivery profiles need to be definitively researched for each inhaled drug. There is a strong need to develop new engineered drug inhalation devices well-matched with improved drug formulations for the treatment of rhinitis or sinusitis.

[Hexadactylism of the four limbs: a case report]. / Esadattilia dei quattro arti: un insolito caso.

An unusual case of postaxial hexadactylism of the hands and feet in one female Caucasian neonate is described. The clinical picture was characterized by symmetrical duplication of the 5th finger in both hands and of the 4th finger in both feet. Malformations of the extremities both in the paternal and in the maternal family were reported. No other associated malformations have been found in the baby and her karyotype was normal. The performed analysis of the literature confirmed the peculiarity of the associated features of this case.

Delivery of nebulized budesonide is affected by nebulizer type and breathing pattern.

The aim of this study was to determine the output in-vitro of budesonide from two different nebulizers under simulated breathing conditions. The BimboNeb and Nebula nebulizers were used to nebulize 2 mL of budesonide (500 microg) suspension. Particle size was determined by inertial impaction after a 5-min nebulization. Total outputs of the drug from both nebulizers were measured using a sinus flow pump to create simulated breathing conditions. Paediatric and adult breathing patterns were used, with drug output measured after 5 and 10 min nebulization. The mass median aerodynamic diameter of budesonide using the BimboNeb (4.5 microm) was significantly greater than that from the Nebula (3.4 microm) (P<0.01). With the simulated adult breathing pattern, the total drug output after 5 min with the BimboNeb (61.5 microg) was twice that from the Nebula (30.7 microg). For the paediatric breathing pattern, total outputs were very similar for both nebulizers. In all cases, nebulizing for 10 min produced greater drug outputs compared with those after 5 min, particularly for the paediatric breathing pattern. The amount of aerosolized drug available for inhalation needs to be assessed for each nebuliser used and the effect of the patient's breathing pattern should also be taken into account.

Oxidative response and membrane modification of diabetic platelets challenged with PAF.

Alterations in the functional activities of platelets (PLT) in type I diabetes have been widely observed. These changes play a key role in the development of cardiovascular complications in diabetes. Various functional activities of PLT are the result of the interaction of numerous stimuli with PLT plasma membrane. This study was designed to evaluate the oxidative response and membrane modifications of diabetic PLT stimulated by platelet activating factor (PAF). The oxidative response was assessed by employing luminol- and lucigenin-amplified chemiluminescence. Luminol-amplified chemiluminescence is sensitive to the release of hydrogen peroxide whereas lucigenin-amplified chemiluminescence is sensitive to the production of superoxide anion. Membrane fluidity and polarity were studied using fluorescence spectroscopy. Membrane fluidity was investigated by measuring steady-state fluorescence anisotropy of 1-[4-trimethylammonium-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and membrane polarity was studied by measuring the steady-state fluorescence emission and excitation spectra of 2-dimethylamino[6-lauroyl]-naphthalene (Laurdan). The diabetic group consisted of 20 type I diabetic children with good metabolic control. Our results show a significant decrease in the luminol- and lucigenin-amplified chemiluminescence of PAF stimulated PLT in the diabetic group with respect to controls. These data indicate a decrement in the release of reactive oxygen species by diabetic PLT. We observed a significant increase in steady-state fluorescence anisotropy of diabetic PLT membrane that reflects a decrease in membrane fluidity. Laurdan showed a blue shift of the fluorescence emission and excitation spectra in diabetic PLT with respect to the control group, indicating a decrease in membrane polarity. The addition of PAF to PLT induced a red shift of Laurdan spectra in both groups, indicating an increase in membrane polarity. Our study [table: see text] demonstrates an altered oxidative response to PAF stimulation of diabetic PLT, probably due to altered generation or handling of reactive oxygen species, and alterations in the physico-chemical properties of the plasma membrane which could influence various functional activities of PLT.

Plasma membrane polarity of polymorphonuclear leucocytes from children with primary ciliary dyskinesia.

BACKGROUND: Polymorphonuclear leucocytes (PMN) from subjects with primary ciliary dyskinesia (PCD) can have abnormal locomotory systems. The locomotory activity of PMN is the result of biochemical events mediated by the plasma membrane. In this study we investigated plasma membrane polarity of PMN from children with PCD. DESIGN: Membrane polarity was studied in 11 children with PCD and in healthy controls by measuring the steady-state fluorescence excitation and emission spectra of 2-dimethylamino[6-lauroyl]naphthalene (Laurdan), which is known to be incorporated at the hydrophobic-hydrophilic interface of the bilayer, displaying spectral sensitivity to the polarity of its surroundings. Laurdan shows a marked steady-state emission red shift in polar solvents, with respect to nonpolar solvents. Moreover, the effect of the microtubule disassembling agent colchicine on PMN membrane polarity was evaluated. RESULT: Our results show a red shift of the fluorescence excitation and emission spectra of Laurdan in PMN from the PCD group with respect to the control group. These data indicate an increase in membrane polarity of PMN from the PCD group. Treatment of PMN with colchicine induced a red shift in the Laurdan excitation and emission spectra with the same trend observed in PMN from the PCD group. CONCLUSION: PMN from children with PCD are characterized by an increased plasma membrane polarity. These changes could be the basis of the modifications in the locomotory activities of PMN. The observed alterations may be attributed to abnormalities in the cytoskeleton.

Plasma membrane fluidity and polarity of polymorphonuclear leukocytes from children with type I diabetes mellitus.

Polymorphonuclear leukocytes (PMN) from diabetic subjects have been found to be abnormal in various functional activities. These activities are mediated by the plasma membrane. This study was designed to evaluate plasma membrane fluidity and polarity in children with type I diabetes mellitus using fluorescence spectroscopy. PMN membrane fluidity and polarity were assessed in a group of 32 diabetic children. Membrane fluidity was investigated by measuring steady-state fluorescence anisotropy and fluorescence decay of 1-[4-trimethylammonium-phenyl]-6-phenyl- 1,3,5-hexatriene (TMA-DPH), whereas membrane polarity was studied by measuring the steady-state fluorescence emission and excitation spectra of 2-dimethylamino[6-lauroyl]-naphthalene (Laurdan). TMA-DPH and Laurdan are known to be incorporated at the hydrophobic-hydrophilic interface of the bilayer. Our data show a significant increase in steady-state fluorescence anisotropy in diabetic PMN that reflects a decrease in membrane fluidity, and a decrease in TMA-DPH lifetime distribution indicating a decrease in membrane heterogeneity. Laurdan shows a blue shift of the fluorescence emission and a red shift of the excitation spectra in diabetic PMN with respect to the control group, indicating a decrease in membrane polarity. The results demonstrate a decrease in the phospholipid order at the membrane surface and a decrease in membrane polarity in diabetic PMN. These alterations in the physico-chemical properties of the plasma membrane could be the basis of the modifications in functional activities of PMN. The changes in the plasma membrane of PMN could be the result of metabolic and chemical modification associated with type I diabetes.

Minor cerebral alterations observed by magnetic resonance imaging in syndromic children with mental retardation.

OBJECTIVE: To evaluate the anomalies of the central nervous system (CNS) by magnetic resonance imaging (MRI) in normal subjects and in syndromic patients. METHODS AND MATERIAL: Seventy-three normal subjects and 50 different syndromic patients with mental retardation (from 3 months to 16 years) were studied utilizing several morphometric parameters (degree of myelination of the white matter, evaluation of liquoral spaces, septo-caudate distance, Evans index, Aboulezz method, and length, width and angles of corpus callosum). RESULTS: A high frequency of anomalies of the corpus callosum, the Chiari anomaly and alterations either of the white matter or of the ventricular and periencephalic system have been observed. CONCLUSION: The authors point out the importance of cerebral MRI in the study of CNS in patients with malformation syndromes. The present research, carried out on a large number of both normal subjects and patients with malformation syndromes, represents one of the first systematic studies in this field.

Antioxidant activities of different hemoglobin derivatives.

The antioxidant activity of hemoglobin was examined by studying both its peroxidase activity and its interaction with the superoxide anion. The peroxidase activity of both the subunits (alpha and beta) was reduced with respect to the alpha 2 beta 2 tetramer and heme-oxidation was found to be associated with a decrease in this activity. Lucigenin-amplified chemiluminescence experiments have shown that at low pH, the presence of hemoglobin reduces the level of superoxide anion generated by the xanthine/xanthine oxidase system (met-Hb is more efficient in reducing the level of O2- than oxy-hemoglobin). These results confirm that hemoglobin may be of importance in providing protection against oxidative damage to erythrocytes.

[Protective effect of oxatomide in infantile bronchial asthma. Double-blind study vs placebo]. / Effetto protettivo dell'oxatomide sull'asma bronchiale infantile. Studio in doppio cieco verso placebo.

BACKGROUND: This study has been designed to assess the protective effect of oxatomide in allergic bronchial asthma of the seasonal type in young children. METHODS: The study was carried out in a paediatric clinic; sixteen children divided into two balanced groups took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, or placebo for a period of 2 months. Eight patients (7 males, 1 female), aged 22 months +/- 2.83 (mean +/- SD) took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, while the other eight (3 males, 5 females; 22.13 months +/- 3.48) took placebo. Efficacy was assessed by monitoring cough, dyspnea at rest, dyspnea following exercise, wheezing, sleep disorders at baseline and after 15, 30 and 60 days of treatment, on the basis of a semiquantitative scale. All side effects were recorded. RESULTS: Persistent coughing was significantly reduced (p < 0.05) after two weeks' treatment with oxatomide. Sleep disorders and other symptoms remarkably improved. Dyspnea at rest and following exercise disappeared after 15 days' therapy, while the intensity of wheezing decreased after 30 days' active treatment. In all parameters examined, oxatomide was significantly more active than placebo at the first examination (p < 0.05 and p < 0.01). Oxatomide was well tolerated and only 2 patients complained of drowsiness which required a reduction in dosage. CONCLUSIONS: Oxatomide, at the dose of 1 mg/kg/day, obtained a good control of respiratory symptoms.

Interaction of trout hemoglobin with H2O2: a chemiluminescence study.

Erythrocytes from trout Salmo irideus are characterized by four different hemoglobin components (HbI, HbII, HbIII and HbIV), HbI and HbIV being predominant. In this study we describe the interaction between trout hemoglobin (HbI and HbIV) and H2O2 using a chemiluminescence assay. Our data show that the reaction of hemoglobins with H2O2 produces a time-limited and significant increase of chemiluminescence signal. The half-life of the decay of this chemiluminescence signal was characteristic for each type of hemoglobin used. These results indicate the formation of excited molecules related to the interaction between trout hemoglobin and H2O2.

Platelet plasma membrane in subjects with primary nocturnal enuresis: effect of desmopressin.

Plasma membrane fluidity of platelets (PLT) obtained from subjects with primary nocturnal enuresis (PNE) and healthy controls was investigated before and after addition of desmopressin (DDAVP). Membrane fluidity was studied by measuring steady-state fluorescence anisotropy of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3, 5-hexatriene incorporated into PLT plasma membrane. Our results show an increase in membrane fluidity at the surface level of PLT from subjects with PNE. Moreover, the addition of DDAVP induces a stable and significant decrease of membrane fluidity in both groups. These results suggest alterations of the lipid order in the exterior part of the PLT plasma membrane from patients with PNE.

Effect of inhaled nedocromil sodium therapy on blood gas changes in children challenged with ultrasonically nebulized distilled water. A comparison of 8 mg versus 16 mg daily dose.

Changes in time course of blood partial pressures of oxygen (PtcO2) and carbon dioxide (PtcCO2) before, during and after challenge with ultrasonically nebulized distilled water (UNDW) were evaluated in 22 children with mild asthma in basal conditions, and after 8 weeks of therapy with inhaled nedocromil sodium at a daily dosage of 8 or 16 mg. PtcO2 and PtcCO2 were followed using transcutaneous O2 and CO2 monitoring system. All asthmatic subjects presented a significant decrease in PtcO2 and/or PtcCO2 (> 20% basal value) during or after challenge. After therapy, the decrease in PtcO2 and PtcCO2 was normalized in the group treated with 16 mg/day, whereas only a partial yet significant reduction in the decrease of O2 and CO2 was observed in the group assuming 8 mg/-day. These data indicate that inhaled nedocromil is effective in treating bronchial hyperresponsiveness in childhood and that the dose required to achieve this effect is of 16 mg/day.

A sensitive detection of neutrophil activation by fluorescence quenching of membrane inserted singlet oxygen probe.

Fluorescence emission intensity of 1,3-diphenylisobenzofuran incorporated in polymorphonuclear granulocytes plasma membranes was investigated in basal conditions and during stimulation with different activators. Phorbol myristate acetate, known as the most effective "oxygen burst" inducer, produced a larger decrease in 1,3-diphenylisobenzofuran fluorescence intensity than 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) and N-formyl-methionyl-leucyl-phenylalanine, known as weak stimulants of oxygen uptake. Diphenyl iodonium an inhibitor of leukocyte NADPH oxidase, and the singlet oxygen selective trap alpha-terpinene inhibited the quenching effect of phorbol myristate acetate on 1,3-diphenylisobenzofuran fluorescence. These data suggest formation of singlet oxygen in activated leukocytes and demonstrate that measurement of 1,3-diphenylisobenzofuran fluorescence intensity provides a new sensitive method of detection of neutrophils activation.

Respiratory distress in a newborn with primary ciliary dyskinesia, situs inversus and Turner syndrome.

A report is given of a newborn girl with situs inversus and Turner syndrome that presented respiratory distress. The patient had a mosaic karyotype 45,X/46,X + mar (80%/20%). Ciliary motion analysis demonstrated a total absence of ciliary motion whereas, ultrastructural studies revealed typical features of primary ciliary dyskinesia (PCD) (absence or short outer/inner dynein arms in 90% of the cilia). We regard this rare combination (PCD, situs inversus and Turner syndrome) as a coincidental occurrence.

Successful interferon gamma therapy in a patient with X-linked chronic granulomatous disease, McLeod syndrome and hyper-IgE. Case report.

Recent studies have shown clinical benefit resulting from recombinant interferon gamma (rIFN-gamma) therapy in patients affected by chronic granulomatous disease (CGD), which represents an important adjunct to conventional therapy. In order to evaluate the effect of interferon gamma therapy, we investigated clinical and haematological parameters in a child with X-linked CGD, McLeod phenotype (kell negative) and hyper-IgE, before and after 8 months of therapy. Our results show no significant effect of rIFN-gamma on the respiratory burst of peripheral polymorphonuclear leukocytes. This notwithstanding, we observed improved clinical and haematological conditions. These results support the view that interferon gamma may benefit these subjects by influencing oxygen-independent antimicrobial activity or other immunological parameters.

Polymorphonuclear leukocyte-generated oxygen metabolites decrease beat frequency of human respiratory cilia.

We investigated the effect of polymorphonuclear leukocyte (PMN)-generated oxygen metabolites on the ciliary beat frequency. PMNs were incubated with human respiratory cilia obtained by nasal brushing. The oxidative metabolism was stimulated by opsonized zymosan, and ciliary beat frequency was evaluated before and after activation of PMNs. Ciliary beat frequency was studied using video microscopy. Our results demonstrate a significant decrease in ciliary beat frequency after activation of PMNs. This effect was reduced by catalase. These data suggest that the PMN-generated oxygen metabolites, particularly H2O2, decrease beat frequency of human respiratory cilia.

A study of the Interaction Between Cetirizine and Plasma Membrane of Eosinophils, Neutrophils, Platelets and Lymphocytes using A fluorescence Technique.

The effect of cetirizine on plasma membrane fluidity and heterogeneity of human eosinophils, neutrophils, platelets and lymphocytes was investigated using a fluorescence technique. Membrane fluidity and heterogeneity were studied by measuring the steady-state fluorescence anisotropy and fluorescence decay of 1-(4- trimethylammonium-phenyl)-6-phenyl-1, 3, 5-hexatriene (TMA-DPH) incorporated in the membrane. The results demonstrate that cetirizine (1 mug/ml) induced a significant increase in the Hpid order in the exterior part of the membrane and a decrease in membrane heterogeneity in eosinophils, neutrophils and platelets. Moreover, cetirizine blocked the PAF induced changes in membrane fluidity in these cells. Cetirizine did not influence significantly the plasma membrane of lymphocytes. These data may partially explain the effect ofcetirizine on inflammatory cell activities.