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Biomedical subjects

S Perrone

Publications and source records attributed to S Perrone.

At least 19 recordsLinked to original sources

Early oxidative stress in amniotic fluid of pregnancies with Down syndrome.

OBJECTIVE: Some evidence suggests that oxidative stress, due to an imbalance between oxidants and antioxidants, occurs in babies with Down syndrome (DS). This study tests the hypothesis that oxidative stress occurs early in DS pregnancies. DESIGN AND METHODS: Isoprostanes (IPs), a new marker of free radical-catalyzed lipid peroxidation, were measured in amniotic fluid from pregnancies with normal, growth restricted and DS fetuses, diagnosed by karyotype analysis of amniotic cells cultured. RESULTS: A nine-fold increase in IP concentrations was found in amniotic fluid of pregnancies with DS fetuses. This increase (595.15; 542.96-631.64 pg/ml, median; 95% CI), was greater than in pregnancies with fetal growth-restricted fetuses (155; 130.57-172.23 pg/ml, median; 95% CI) and normal fetuses (67; 49.82-98.38 pg/ml, median; 95% CI; p<0.0001). CONCLUSIONS: The study reveals that oxidative stress occurs early in pregnancy and supports the idea of testing whether prenatal antioxidant therapy may prevent or delay the onset of oxidative stress diseases in the DS population.

Adult↗

Neonatal pain analyzer: development and validation.

We developed a pain analyzer (ABC analyzer) to perform automatic acoustic analysis of neonatal crying and to provide an objective estimate of neonatal pain. The ABC analyzer uses a validated pain scale (ABC scale) based on three acoustic parameters: pitch frequency, normalized RMS amplitude, and presence of a characteristic frequency- and amplitude-modulated crying feature, defined as "siren cry". Here we assessed the reliability of the analyzer. We enrolled 57 healthy neonates. Each baby was recorded with a video camera during heel prick. Pain intensity was evaluated using a validated scale [Douleur Aigue du Nouveau-Né (DAN) scale] and the analyzer and the two scores were compared. We found a statistically significant concordance between the DAN score and ABC analyzer score (p < 0.0001). The ABC analyser is a novel approach to cry analysis that should now have its properties carefully evaluated in a series of studies, just as is necessary in the development of any other pain measurement tool.

Acoustics↗

Non protein bound iron concentrations in amniotic fluid.

OBJECTIVES: To investigate whether amniotic fluid concentrations of non protein bound iron (NPBI) vary with growth in healthy fetuses and also offer a reference curve in the second trimester of pregnancy. DESIGN AND METHODS: Amniotic fluid concentrations of NPBI were measured by HPLC in 118 women with physiological singleton pregnancies, who underwent amniocentesis for fetal karyotype between weeks 15 and 18 of gestation. RESULTS: NPBI increased progressively from weeks 14--15 to weeks 15--16, peaking at 17--18 weeks of gestation. NPBI values regressed positively with gestational age (GA). Multiple linear regression analysis between NPBI, as dependent variable, and various fetal parameters, as independent variables, showed a statistically significant regression coefficient with GA, bi-parietal diameter and transverse cerebellar diameter. CONCLUSIONS: The present data constitutes the first quantification of NPBI concentrations in amniotic fluid under physiological conditions. Correlations with GA and ultrasound fetal biometry suggest that NPBI may play a role in fetal growth.

Adult↗

Ante partum bed rest and unexplained infantile crying.

AIM: The aim of this study was to assess whether bed rest during pregnancy is a risk factor for infantile colics. METHODS: In a previous paper a questionnaire was administered to 86 women (43 of whom had stayed in bed during pregnancy for a mean of 3.4+/-1.2 months, and 43 were controls) about the clinical history and the present state of their 11-15 year old babies. In the present paper we traced these women and assessed the presence/absence of unexplained infant crying (UIC, infantile colic), diagnosed by a physician in the first year of life of these children. Forty mothers answered the inquiry, and we compared their answers with 40 control mothers. RESULTS: Babies born after maternal bed rest during pregnancy had a higher incidence of UIC than the control group (26/40 vs 11/40; P=0.0015). No significant correlation was found between UIC and allergies or between UIC and maternal or artificial breast feeding. CONCLUSIONS: Our retrospective study shows a possible association between bed rest and UIC: further studies, including other important variables (stress, drugs, smoking) are needed.

Bed Rest↗

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

Adult↗

Clinical evaluation of internal hemodiafiltration (iHDF): a diffusive-convective technique performed with internal filtration enhanced high-flux dialyzers.

AIM: Efficiency in removing middle molecules such as beta2-microglobulin (beta2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration/back filtration phenomenon can be used. The recent development of a so-called "internal filtration enhanced dialyser" prompted us to compare the removal of beta2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF). METHODS: Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and beta2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane. RESULTS: No significant differences have been observed in removal rate switching from HDF to iHDF except for beta2-MG removal, which was slightly higher in HDF than in iHDF Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average). CONCLUSIONS: iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.

Aged↗

Encephalocraniocutaneous lipomatosis (Haberland syndrome) with bilateral cutaneous and visceral involvement.

Encephalocraniocutaneous lipomatosis, or Haberland syndrome, is a rare congenital neurocutaneous disease. It is characterized clinically by unilateral lipomatous hamartomata of the scalp, eyelid, and outer globe of the eye, ipsilateral porencephalic cysts with cortical atrophy, cranial asymmetry, marked developmental delay and mental retardation. This syndrome should be distinguished from other mosaic neurocutaneous phenotypes such as as Delleman syndrome, Schimmelpenning syndrome, Goltz syndrome, Goldenhar syndrome and Proteus syndrome. Here we report a case of Haberland syndrome with bilateral involvement which underscores the extreme heterogeneity of clinical presentation of this and related syndromes.

Biopsy↗

Oxidant injury in neonatal erythrocytes during the perinatal period.

UNLABELLED: It has been known for many decades that oxidative stress leads to oxidation of hemoglobin and damage to the erythrocyte membrane. More recently, the factors involved in denaturating of membrane proteins and lipid peroxidation have been investigated in detail, as well as the mechanism of reactive oxygen species formation in red cells. Oxidative stress depletes adenosine triphosphate (ATP) and adenine nucleotides, whereas adenosine monophosphate (AMP) deaminase seems to depress energy metabolism by blocking the salvage pathway of purine nucleotides. Depletion of ATP and activation of AMP deaminase are related to calcium ion concentrations. Denaturating of membrane proteins generally precedes lipid peroxidation and consequent phagocytosis due to caspase activation. Extensive investigations demonstrated the key role of oxidative stress and iron release in a reactive form causing membrane protein damage via the Fenton reaction and hydroxyl radical production. In the absence of efficient protection by antioxidant factors and other molecules such as flavonoids, oxidative stress is responsible for the release of iron in reactive form, predisposing red cells to hemolysis through the formation of senescence antigen. Other well-known sources of oxidative stress in red cells are free radical production outside the red cell by activated phagocytes, endothelial metabolism, hyperoxia, ischemia-reperfusion and the arachidonic acid cascade. CONCLUSION: The recent insight into the mechanism of oxidative injury of red cells and evidence of relationships between erythrocyte oxidative stress and hypoxia suggest that increased hemolysis is induced by severe hypoxia and acidosis in the fetus as well as the newborn.

Asphyxia Neonatorum↗

New biomarkers of fetal-neonatal hypoxic stress.

UNLABELLED: The complex pathophysiological mechanisms underlying perinatal hypoxia make it difficult to define early markers of severe hypoxia-ischemia encephalopathy. However, as progress in the development of neuroprotective therapeutic measures continues, the early identification of neonates at risk of severe hypoxic-ischemic encephalopathy is an important goal for appropriate decision making. Although the timing of perinatal hypoxic brain damage may vary and is sometimes unknown, high levels of non-protein-bound iron and high nucleated red blood cell counts in cord blood indicate an antepartum origin of neurological impairment, because they can occur only as a consequence of a pre-existing asphyxic event. CONCLUSION: The combined assessment of nucleated red blood cells and non-protein-bound iron at birth seems extremely useful for the early identification of newborns at high risk of brain damage. Activin A also seems to be a reliable marker of perinatal hypoxia. Prospective long-term follow-up studies are needed to verify their predictive role.

Activins↗

Free radicals and brain damage in the newborn.

Newborns and particularly preterm infants are at high risk of oxidative stress and they are very susceptible to free radical oxidative damage. Indeed, there is evidence of an imbalance between antioxidant- and oxidant-generating systems which causes oxidative damage. The brain may be especially at risk of free radical-mediated injury because neuronal membranes are rich in polyunsaturated fatty acids and because the human newborn has a relative deficiency of brain superoxide dismutase and glutathione peroxidase. The brain of the term fetus is at higher risk of oxidative stress than that of the preterm fetus, as a consequence of its higher concentration of polyunsaturated fatty acids and the maturity of the N-methyl-D-aspartate receptor system at term. There seems to be a maturation-dependent window of vulnerability to free radical attack during oligodendrocyte development. Early in its differentiation, the oligodendrocyte may be vulnerable because of active acquisition of iron for differentiation at a time of relative delay in the development of certain key antioxidant defenses in the brain. Excess free iron and deficient iron-binding and -metabolizing capacity are additional features favoring oxidant stress in premature infants. Free radicals may be generated by different mechanisms, such as ischemia-reperfusion, neutrophil and macrophage activation, Fenton chemistry, endothelial cell xanthine oxidase, free fatty acid and prostaglandin metabolism and hypoxia. Reactive oxidant production by these different mechanisms contributes in a piecewise manner to the pathogenesis of perinatal brain injury.

Brain Diseases↗

Red blood cell involvement in fetal/neonatal hypoxia.

Free radical release plays an important role in the development of brain injury following hypoxic-ischemic encephalopathy. It causes endothelial cell damage and anomalies in NMDA receptors, synaptosome structure and astrocyte function. Mitochondrial dysfunctions caused by asphyxia, reperfusion after ischemia, arachidonic acid cascade, catecholamine metabolism and phagocyte activation are known sources of reactive oxygen species, particularly the superoxide anion (O2(-)). O2(-) mainly induces peroxidation by the Fenton/Haber Weiss reaction or via iron-oxygen complexes. Since both reactions require reactive heavy metals, non-protein-bound iron (NPBI) is essential for the induction of lipid peroxidation. Experimental studies have demonstrated the neurotoxicity of iron in ischemia-reperfusion. Normal axonal transport of brain iron is also reported to be disrupted in hypoxia-ischemia, leading to a buildup of iron in the white matter. The free iron content of erythrocytes (ICRBC) is considered a marker of oxidative stress. Free iron release is accompanied by the oxidation of membrane proteins and the appearance of senescent antigen, as measured by autologous IgG binding. Our preliminary results suggest a significant positive correlation between plasma free iron and the number of nucleated red cells in cord blood, currently considered a reliable index of lasting intrauterine asphyxia but also possessing a high predictive value for poor neurodevelopmental outcome. The rate of erythropoiesis and the entity of ICRBC are related to the degree of asphyxia and the probability of neurological impairment. Since even an increase in NPBI during asphyxia is related to a poor outcome, iron released by red cells could possibly also contribute to NPBI levels.

Asphyxia Neonatorum↗

[Free radicals and brain damage in newborns with hypoxic-ischemic lesion].

Free radicals (FR) are highly reactive chemical molecules containing one or more unpaired electrons. Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), are normally produced in living organisms. When over produced, they are major mediators of cell and tissue injury. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress in vivo is a degenerative process due to the over production and propagation of FR reactions. FR reactions lead to oxidation of lipids, proteins, polysaccharides and to DNA damage. Newborns and particularly preterm infants are very susceptible to FR oxidative damage. In these subjects, there is evidence of an imbalance between antioxidant and oxidant-generating systems enhancing oxidant injury.

Brain Damage, Chronic↗

Early diagnosis of recurrence of Trypanosoma cruzi infection by polymerase chain reaction after heart transplantation of a chronic Chagas' heart disease patient.

Heart transplantation is contraindicated as an effective treatment for end-stage Chagas' heart disease because of post-operative recurrence of Trypanosoma cruzi infection and reactivation of disease after immunosupression. In a follow-up study of a heart transplanted patient with Chagas' disease, we prospectively evaluated the usefulness of the polymerase chain reaction (PCR) for early diagnosis of reactivation. We monitored post-operative recurrence of Trypanosoma cruzi infection with microscopic observation of the parasite in peripheral blood (Strout's method), endomyocardial biopsies (EMBs), skin lesions, and 2 PCR assays, based on the amplification of specific T cruzi kinetoplastid and nuclear DNA sequences. During follow-up, parasite DNA was amplified in blood samples and EMB sections 41 days before we observed patent parasitemia and cutaneous manifestations of reactivation, proving that PCR is much more sensitive than direct microscopic observation for early diagnosis of disease reactivation in heart-transplanted Chagas' disease patients.

Animals↗

Biofilms invade nephrology: effects in hemodialysis.

Bacteria attach to surfaces and aggregate in a biopolymer matrix to form biofilm. Studies on biofilm have shown its presence in many prosthetic devices used in nephrology as well as in fluid pathways of hemodialysis plants and monitors. Once present, this community of bacteria increases resistance to biocide due to slime production and, as a result, chemical products for dialysis monitor disinfection and descaling procedures do not result in an effective treatment. Ultrapure dialysate is a goal in modern hemodialysis, and ultrafiltration is used to obtain sterile and apyrogen fluids. Microbial colonisation of ultrafilters may occur if, due to inadequate disinfection protocols, membrane is exposed to persistent bacterial contamination, and biofilm is allowed to form and to grow. As more and more data link final dialysate microbial contamination to clinical effects of bioincompatibility from chronic inflammation in dialysis patients, attention has to be focused on possibilities of biofilm avoidance.

Biofilms↗

Total hydroperoxide and advanced oxidation protein products in preterm hypoxic babies.

Previous studies have shown that plasma lipoproteins are a common target of free radical-induced oxidative stress in hypoxic newborn infants. In contrast to lipids, the reaction of proteins with various oxidants during hypoxia has not been extensively studied. We tested the hypothesis that tissue hypoxia results in increased production of protein oxidation in cord blood of preterm newborns. Heparinized blood samples of 39 hypoxic and 16 control preterm newborns were obtained from the umbilical vein, after cord clamping immediately after delivery. Plasma levels of total hydroperoxide (TH), advanced oxidation protein products (AOPP), hypoxanthine (Hx), xanthine (Xa), and uric acid (UA) were measured. Higher Hx, Xa, UA, TH, and AOPP levels were found in hypoxic newborn infants than in controls. Statistically significant correlations were observed between: TH and Hx (r = 0.54, p = 0.003, n = 28), AOPP and Hx (r = 0.64, p = 0.0001, n = 27), and TH and AOPP plasma levels (r = 0.50, p = 0.02, n = 21). In summary, TH, AOPP, Hx, Xa, and UA production is increased in fetal blood during hypoxia. The more severe the hypoxia, the higher the lipid and protein damage by free radicals.

Blood Proteins↗

[Pre- and post-natal corticosteroids: side effects].

It is well known that prenatal steroid therapy (ST) reduces the mortality rate and the incidence of respiratory distress syndrome and intraventricular haemorrhage in premature infants. The benefits and safety of repeated courses of antenatal ST are doubtful due to possible side effects in the mother and baby. Experimental studies in animals have shown that multiple courses of antenatal ST have deleterious effects on lung growth and organisation, brain myelination, hypothalamic-pituitary-adrenal function and retina development. In humans, exposure to multiple courses of antenatal ST is associated with small head circumference at birth and increased incidence of maternal endometritis and early-onset neonatal sepsis. When administered soon after birth, ST may enable a reduction in ventilator settings and facilitate weaning from mechanical ventilation, but although associated with rapid improvement in lung function, it does not modify mortality or long-term outcome and has many acute side effects. Deleterious effects on lung maturation and neuro-developmental outcome, including cerebral palsy, have also been reported. The paucity of follow-up data is a major problem, and further prospective trials are needed.

Adrenal Cortex Hormones↗

Mesenteric cystic neoformations: report of two cases.

The authors present two case reports of mesenteric cystic neoformations which they themselves observed and, with the help of the literature regarding this pathology, discuss the problems of both diagnosis and treatment.

Adult↗