Transition from ziprasidone im to oral formulation in agitated patients with acute exacerbation of schizophrenia: an open trial.

INTRODUCTION: A transition from IM to oral formulation of an antipsychotic agent is often required during the long-term management of schizophrenia. This multicenter trial evaluates the IM/oral sequential administration of ziprasidone in agitated subjects with an exacerbation of schizophrenia. METHODS: Adult patients requiring IM therapy for schizophrenic symptoms were assigned to IM ziprasidone 10 mg for 3 days, followed by oral ziprasidone (initial dose: 80 mg/day) for 8 weeks. The primary efficacy outcomes were the change in the total PANSS and in the CGI-S scores vs. baseline values. RESULTS: In total, 150 patients were included in the study. A decline in the PANSS and CGI-S scores was observed throughout the study (p < 0.0001 vs. baseline): these reductions became significant at the point of transition from IM to oral formulation (p < 0.0001 vs. baseline). DISCUSSION: Even with the limitations of any non-comparative study, these results suggest that the IM/oral sequential administration of ziprasidone is an effective and well tolerated therapeutic option in the management of acute exacerbations of schizophrenia in agitated patients.

Delayed closure of ductus arteriosus in term newborns with congenital hypothyroidism: effect of L-thyroxine therapy.

Congenital hypothyroidism is associated with increased incidence of congenital defects (15.6%), frequently involving the heart (5.8%). Only few studies have evaluated the association between congenital hypothyroidism and patent ductus arteriosus. We report on two term newborns affected by thyroid agenesis and patent ductus arteriosus that closed after starting L-thyroxine substitutive therapy. This association suggests a close relation between hypothyroidism and patent ductus arteriosus. Hypothyroidism should be considered in term infants with patent ductus arteriosus because thyroid hormone production is among the prerequisites for postnatal ductal closure.

Early low-dose hydrocortisone in very preterm infants: a randomized, placebo-controlled trial.

BACKGROUND: Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension. Low-dose hydrocortisone (HC) may allow for beneficial effects. OBJECTIVE: Our aim was to assess whether HC is able to increase survival without chronic lung disease. METHODS: We performed a double-blind, randomized, placebo-controlled trial. Fifty mechanically ventilated infants (birth weight: 500-1,249 g) were randomized to receive treatment (HC 0.5 mg/kg/12 h for 9 days, then HC 0.5 mg/kg/24 h for 3 days) or placebo. Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age (O(2)-free survival). RESULTS: The basic characteristics were similar between the two groups. O(2)-free survival was higher in the HC group (64 vs. 32%). The advantage was particularly evident among infants without antenatal steroids. The mortality rate was 16% in the HC group versus 40% in the control group (difference not significant). Hypotension after recruitment was reduced by HC (0 vs. 30%). The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups. CONCLUSIONS: HC prophylaxis improved O(2)-free survival and early cardiocirculatory function in our population, without important short-term effects. The neurodevelopmental outcome will be assessed at 2 years.

Does calprotectin represent a regulatory factor in host defense or a drug target in inflammatory disease?

Calprotectin, a protein composed by two subunits of 8 and 14 kD respectively, is released by neutrophils in the biological fluids under inflammatory states. For instance, detection of calprotectin in faeces represents a diagnostic tool in the case of inflammatory bowel disease. Quite interestingly, calprotectin is increased in the stool of healthy newborns from day three up to day thirty and, physiologically, this increase may be interpreted as a defense mechanism against yeast and fungi. Therapeutic attempts at inhibiting the deleterious effect of calprotectin have been experimentally made by using lycoricinidol. This natural compound is able to hamper the calprotectin-induced apoptosis on the one hand. On the other hand, the same compound plays a prophylactic role in the course of experimental arthritis in rats.

Multichannel intraluminal impedance to detect relationship between gastroesophageal reflux and apnoea of prematurity.

BACKGROUND: The association between gastroesophageal reflux and apnoea of prematurity is still controversial. Available data are biased by the heterogeneity of the infants enrolled as regard to some confounding factors and by the use of the traditional pH monitoring that is unable to detect non acid reflux events which might be prevalent in infants receiving frequent milk feeding. Multichannel intraluminal impedance has been recently introduced as a pH-independent method to investigate the bolus transport in hollow organs. OBJECTIVE: To assess if combined multichannel intraluminal impedance-pH study could be useful to detect an association between gastroesophageal reflux and apnoea of prematurity. METHODS: We prospectively evaluated a group of premature infants with apnoea of prematurity in absence of any confounding factors (ventilatory support, treatment with caffeine, permanent nasogastric tube, post-natal age older than 30 days) by simultaneous recording of 24-h multichannel intraluminal impedance-pH and cardiorespiratory monitoring. A temporal relationship between an apnoea and a reflux event was considered if both commenced within 20s of each other. RESULTS: Six premature infants [three male; median gestational age 31 weeks (range 27-36); birth weight 1335g (range 1200-2350); age at study 17 days (range 7-28)] were studied. A total of 405 reflux events [306 (76%) weakly acid and 99 acid reflux] and 142 apnoeas were detected. The frequency of apnoeas occurring during the reflux events period was significantly greater than the one calculated for reflux-free period [0.42/min (0.00-1.28) versus 0.016/min (0.003-0.028); p<0.05]. The sub-analysis based on chemical composition and duration of refluxate showed that the frequency of apnoeas associated with weakly acid reflux events was significantly greater than the one calculated for reflux-free period [0.416/min (0.00-1.30) versus 0.016/min (0.003-0.028), respectively; p<0.05] and that the frequency of apnoeas occurring during reflux events longer than 30s was significantly higher than those occurring during shorter reflux events (22% versus 11%; p<0.004). CONCLUSION: Our data show that weakly acidic reflux events are more prevalent than acid reflux events in premature infants, confirming the need for the use of multichannel intraluminal impedance-pH monitoring for diagnosis of gastroesophageal reflux in those patients. Gastroesophageal reflux and apnoea of prematurity are both common occurrences and, in our experience, may be temporally related especially as regard to weakly acid refluxate and reflux events longer than 30s.

Plasma protein Z levels in healthy and high-risk newborn infants.

AIM: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants. METHODS: A longitudinal observational study was conducted. Inclusion criteria were: healthy term and preterm newborns normal for gestational age and newborns belonging to one of the following groups: newborns small for gestational age (SGA), newborns affected by respiratory distress syndrome (RDS), newborns from mothers with pre-eclampsia. Newborns with sepsis, congenital malformation or haemorrhagic disorders were excluded. Plasma PZ levels, protein C (PC) concentration, PC activity and protein-induced vitamin K absence levels were measured. RESULTS: 53 newborns were enrolled into the study. PZ and PC antigen levels varied significantly among analysed subgroups on day 1 (p < 0.01): lower levels of these inhibitors were found in RDS newborns (group C), newborns from mothers affected by pre-eclampsia (group D) and SGA newborns (group E) than in healthy term and preterm newborns (groups A and B). CONCLUSION: PZ deficiency occurs in newborns affected by severe RDS, in newborns from pre-eclamptic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last condition.

Calprotectin levels in meconium.

AIM: To evaluate the effect of gender, gestational age, birthweight, mode of delivery, 5'-Apgar score and maternal conditions on calprotectin concentrations in meconium. METHODS: Calprotectin was measured in 131 neonates, in the first passed meconium. RESULTS: Calprotectin levels (mean +/- SD) resulted in 145.2 +/- 78.5 mg kg(-1) meconium, significantly correlated with birthweight (r = -0.333; p < 0.001), gestational age (r = -0.206; p = 0.018) and 5'-Apgar score (r = -0.243, p = 0.035). The estimated regression model was: calprotectin levels (mg kg(-1)) = 269.58-41.54 weight (kg): r = 0.383, p < 0.001. No differences were found in relation to gender, mode of delivery and maternal conditions. CONCLUSION: Calprotectin is already present in the first passed meconium, with higher levels in preterm and low birthweight neonates, as well as in neonates with some degree of perinatal asphyxia, as indicated by the negative correlation with 5'-Apgar score. These findings are probably secondary to both the immaturity of the intestinal mucosa and its hypoxic-ischaemic damage.

Vertical transmission of hepatitis C virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective study.

BACKGROUND: Mother to infant transmission of hepatitis C virus (HCV) has been extensively studied in mothers with human immunodeficiency virus (HIV) infection, whereas fewer data are available on the vertical HCV transmission in HIV-negative women. METHODS: Between January 1995 and June 1997, 78 consecutive HCV-positive/HIV-negative women with their offspring entered this prospective study aimed to define the prevalence of and risk factors for HCV vertical transmission. Risk factors for HCV were carefully sought, and HCV viral load and genotype were determined in all positive mothers. The infants were tested for alanine aminotransferase (ALT) and HCV-RNA at birth and at 4, 8, 12, 18, and 24 months of age. RESULTS: Eight of 60 (13.3%) infants born to HCV-RNA positive mothers acquired HCV infection, but only 2 (3,3%) were still infected by the end of follow-up. Infants' genotypes matched that of the mothers. ALT levels were in the normal range in all study subjects throughout the follow-up. High maternal viral load (P < 0.05), possession of HCV risk factors (P < 0.004), and history of blood transfusion (P < 0.05) were associated with increased risk of HCV vertical transmission. CONCLUSIONS: This long-term prospective study shows that, although vertical transmission from HIV-negative mothers occurs in 13% of cases, there is a high rate of spontaneous viral clearance (75%). High maternal viral load and mothers belonging to HCV risk categories were the only variables predictive of the vertical transmission.

Mild ventriculomegaly as a counselling challenge.

OBJECTIVE: Our purpose was to evaluate the outcome of a group of fetuses with mild ventriculomegaly. METHODS: We retrospectively collected all cases of antenatally diagnosed mild enlargement of the lateral cerebral ventricles (transverse diameter of the atrium between 10 and 15 mm) between 1992 and 1997. Cases were included in the study if no other ultrasonic anomalies (including soft markers) were found. TORCH screening, karyotyping, search for associated anomalies and neurological examination (including imaging) were performed. Outcome information was available for all cases up to 30 months. RESULTS: Fourteen cases were examined. TORCH was always negative, 1 case with a microdeletion of chromosome 1 was identified. During the course of pregnancy, 2 fetuses showed progression to frank hydrocephalus. Five cases of agenesis of the corpus callosum, 1 of lissencephaly and 1 of heterotopia were eventually diagnosed. After birth 2 syndromes were identified. Three babies died during the follow-up period, among the survivors 4 had severe neurological damage, 2 of them had no associated dysmorphic findings. DISCUSSION: A heterogeneous group of central nervous system disorders may manifest antenatally as mild ventriculomegaly. The current management may not be able to identify dangerous conditions that present subtle dysmorphic features, or be able to predict abnormal outcome in most of the cases.

Gastric electrical activity and gastric emptying in preterm newborns fed standard and hydrolysate formulas.

BACKGROUND: Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying, the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a standard preterm formula. METHODS: Thirty-six preterm newborns with a gestational age of 32.2 +/- 2.3 weeks were assigned randomly to standard formula or hydrolyzed formula. Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal. All recording sessions were performed 1 week after infants had reached full enteral feeding. RESULTS: No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas. In particular, regurgitation and vomiting were observed in 78% versus 64% of preterm newborns after standard and hydrolyzed formula, respectively (Fisher exact test, not significant). No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups. CONCLUSIONS: It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants.

Renal vein thrombosis in a newborn with prothrombotic genetic risk factors.

Environmental and genetic risk factors interact to cause venous thromboembolism. Renal vein thrombosis in the newborn has been frequently associated with "risk factors" as catheters, surgery or trauma, but it has also been demonstrated a pathogenetic role of genetic prothrombotic risk factors, i.e. activated protein C resistance and FV Leiden. The treatment of neonatal venous thrombosis varies worldwide and different approaches have been proposed. We present a case of renal vein thrombosis in a female newborn with normal plasma levels of protein C, protein S and antithrombin III, but with her genotype characterized by the presence of three prothrombotic risk factors: factor V Leiden, methylentetrahydrofolate reductase and platelet glycoprotein IIIa polymorphisms. The treatment with recombinant tissue plasminogen determined complete thrombus dissolution.

Cord blood endothelin-1 and perinatal asphyxia.

UNLABELLED: Discordant data have been reported on endothelin-1 (ET-1), a potent endothelium-derived vasoconstriction peptide, during the neonatal period, and elevated levels have been found in various neonatal diseases. This study evaluated ET-1 in the cord blood of 74 neonates of different gestational age, birthweight, mode of delivery and 5'-Apgar score. CONCLUSION: Higher ET-1 levels were found in neonates born by emergency caesarean section, and in newborns with low 5'-Apgar score, suggesting that ET-1 could be a marker of perinatal asphyxia.

Dosage regimens of intranasal aerosolized surfactant on otitis media with effusion in an animal model.

OBJECTIVE: To determine optimal dosage regimens of intranasal metered dose aerosolized surfactant with and without other medications in the treatment of otitis media with effusion (OME). STUDY DESIGN: Resolution of experimental OME in gerbils was determined based on otomicroscopy and tympanometry. Experimental intranasal drugs were: surfactant, surfactant with betamethasone, surfactant with phenylephrine, and a normal saline solution placebo. Medications were administered once or twice daily via a metered dose inhaler. RESULTS: For twice-daily dosing, mean days to OME resolution were 8.5 for the aerosolized surfactant, 6.3 for the surfactant with betamethasone, 18.7 for the surfactant with phenylephrine, and 16 each for control and placebo. Resolution with the once-daily dosage was longer for all conditions. Results were comparable using tympanometry. CONCLUSION: OME resolved faster than the natural course when treated with intranasal surfactant with and without steroids. Twice-daily dosing was statistically superior. SIGNIFICANCE: This study reiterates the effectiveness of OME treatment with an aerosolized synthetic surfactant with and without steroids and establishes a superior twice-daily dosage schedule.

Intranasal surfactant aerosol therapy for otitis media with effusion.

OBJECTIVE: To determine the effect of surfactant alone and with other medications delivered intranasally as a metered dose inhaler (MDI) aerosol on the resolution of experimentally induced otitis media with effusion (OME). BACKGROUND: Eustachian tube dysfunction is a primary factor in the pathogenesis of OME. Intranasal surfactant via MDI has been shown in this laboratory to reduce passive opening pressure of the eustachian tube in normal gerbils and mice. STUDY DESIGN: OME was developed in 35 gerbils by transtympanic injection of 10 microg lipopolysaccharide from Klebsiella pneumoniae. Pretreatment otomicroscopy and tympanometry were performed to exclude pre-existing middle ear disease, and postinfection evaluations were performed on alternate days for a period of 30 days. Five animals received no treatment (control group); four were treated with propellant only (placebo); seven received surfactant alone; eight received surfactant and betamethasone; and six received surfactant with phenylephrine. All medications were sprayed intranasally as an aerosolized MDI and administered daily from postinfection day 2 onward. RESULTS: OME resolved after 16.0 +/- 0.44 days (mean + SD) in controls. There was no difference seen in the placebo or the surfactant with phenylephrine groups. Treatment with surfactant yielded resolution in 10.57 +/- 0.37 days; this was reduced to 8.57 +/- 0.37 days with surfactant plus betamethasone. These differences are statistically significant. There was no recurrence of OME in any group. CONCLUSION: This study demonstrates that using an aerosolized MDI surfactant with and without betamethasone decreases the duration of OME in this in vivo gerbil model.

Gastric electrical activity and gastric emptying in term and preterm newborns.

The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28-32 weeks, 11 preterm newborns with a gestational age of 32-36 weeks, and 10 full-term newborns with a gestational age of 36-40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7-92.3) vs. 29.6% (3.7-78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4-87.4), 60.9% (38.1-89.7), 77.8% (66.4-84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T(1/2) was longer in the preterm newborns of 28-32 weeks than preterm newborns of 32-36 weeks and full-term newborns (fasting antral area: 0.96 cm2 (0.6-1.5), 0.63 cm2 (0.4-1.2), 0.55 cm2 (0.1-0.9) respectively, P < 0.05; T(1/2): 83.4 min (76.0-108.5), 70 min (57.5-89.5) and 71.8 min (54.9-81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28-32 weeks compared to full-term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age.

[Echographic measurement of subcutaneous adipose tissue as fetal growth index]. / Misurazione ecografica del tessuto adiposo sottocutaneo come indice di crescita fetale.

OBJECTIVE: To evaluate, by 3rd trimester ultrasound examination, fetal adipose tissue to predict fetal growth and birthweight. PATIENTS AND METHODS: Thirteen pregnant women (group 1) with uncomplicated pregnancy and 9 diabetic women (group 2) have been enrolled. We have examined adipose tissue at the cross sectional level of arm, thigh and abdomen and at the longitudinal sectional level of shoulder. During 3rd trimester measurements were taken at the beginning (28-32 gestational weeks), at the middle (34-38 gestational weeks) and at term (39-41 gestational weeks). At birth we recorded the skinfolds of arm, thigh and shoulder and the neonatal weight. Subsequently, by regression analyses ultrasound parameters of physiological pregnancies were correlated to skinfolds measurements at birth, while abdomen thickness was compared to birthweight. In addition, ultrasound markers of the physiological pregnancies were compared to those of diabetic pregnancies by the t-test. RESULTS: Fetal limbs examination had not a prognostic value at any gestational week. Shoulder ultrasound measurements appeared well correlated to the shoulder skinfold after birth since the 34th week. Diabetic mothers' fetuses presented much more adipose tissue than control cases, particularly of arm and thigh at 28-32 weeks, of shoulder at 34-38 weeks and in all the markers at term pregnancy. CONCLUSION: Ultrasound examination of fetal adipose tissue seems to have a predictive value for fetal growth both in physiological and diabetic pregnancy.

[Blood lead levels during pregnancy in th the newborn period. Study of the population of Bari]. / Livelli ematici di piombo in gravidanza e in età neonatale. Studio della popolazione di Bari.

Blood lead levels during pregnancy and in neonates immediately after birth have been evaluated, showing higher values in mothers compared to neonates (5.81 +/- 3.05 vs 4.87 +/- 3.60 micrograms/100 ml) and a positive correlation between maternal and neonatal levels (r = 0.82). On the basis of the results derived from the population examined, it has been observed that 6% of newborns have blood lead levels higher than 10 micrograms/100 ml a value recently identified by the Centers for Disease Control (CDC, Atlanta, USA) as a limit for toxicity in children. Moreover, neonatal Pb levels were higher than those found in infants from 6 to 12 months (4.87 +/- 3.60 vs 2.24 +/- 0.54 micrograms/100 ml). During the first week of life there is a steady decrease of blood lead levels, together with increasing renal lead excretion. This study was carried out at the "Dipartimento di Biomedicina dell'Età Evolutiva" University of Bari, southern Italy.

Maternal and neonatal lead exposure in southern Italy.

We evaluated the blood lead levels in 159 pregnant women and in their healthy newborns at birth. The blood lead levels were higher in mothers as compared with neonates, with a linear correlation between maternal and neonatal levels. The blood lead levels were also higher in neonates as compared with infants aged 6-12 months, and, besides, 2.5% of the newborns had blood lead levels > 10 microg/dl, the actual level of concern according to the Center for Disease Control. The study of blood and urinary lead levels during the 1st week of life showed a steady decrease of blood lead levels, together with increasing levels of urinary lead. The mechanism of renal elimination is important to avoid persistently high free blood lead levels, with possible deposition in tissues with high lead affinity, such as bone. In newborns, the possibility of a functional renal insufficiency during the first days of life suggests that newborns with high cord blood lead levels and impaired renal function could be at high risk of lead toxicity, so that it could be advisable to perform a careful and prolonged follow-up.

Rapid detection of neonatal sepsis using polymerase chain reaction.

Clinical diagnosis of sepsis in newborn infants is not easy and there is no laboratory test with 100% specificity and sensitivity, with the exception of blood culture, the results of which are not available for at least 48-72 h. Polymerase chain reaction methodology has been used to diagnose different bacterial, viral and protozoal infections, and the possibility of amplifying the DNA region common to all bacteria could represent an optimal method for the diagnosis of sepsis. The authors have performed PCR in a group of 33 neonates at risk for early-onset sepsis, correlating molecular data with blood culture results. The presence of bacterial DNA in blood samples was evaluated, amplifying the DNA region encoding the 16S rRNA. There were no false negative results (four positive blood cultures and four positive PCR), with competitive costs and time. This method also allows the diagnosis of sepsis due to uncommon species and also, using a second PCR with specific primers, an aetiological diagnosis.