Blind serosurvey of HIV antibodies in newborns in 92 Italian hospitals: a method for monitoring the infection rate in women at time of delivery.

In Italy, drug abusers are the major risk category for HIV infection, representing 67% of all the reported cases of AIDS. This can in part explain the higher incidence of the infection observed in Italian females (17.7%) in comparison with the data reported in Europe (11.5%) or in the U.S. (8.5%). Therefore, anti-HIV screening in newborns reflects the serologic pattern of the respective mothers and can provide a useful tool in evaluating the incidence of the infection in a relatively unselected population. Furthermore, the data collected can provide a good predictive parameter for the rate at which pediatric AIDS will develop. Blood samples were collected on filter paper for routine screenings from 39,102 consecutive newborns in 92 hospital nurseries, from eight different Italian regions, during the period June 1988-April 1989. Blood-saturated disks were screened for anti-HIV antibodies (HIV Ab) using an ELISA; positive results were confirmed using a Western blot. Among the 39,102 blood samples tested, 51 (0.00130, 95% confidence intervals, Poisson distribution of 0.00097-0.00171) were found to be positive for HIV Ab. The distribution pattern of the positive samples among the different regions correlates to the cumulative AIDS incidence rate, with a higher prevalence in urban and industrialized areas.

Immunologic follow-up of infants treated with granulocyte transfusion for neonatal sepsis.

The immunologic status and the occurrence of alloimmunization against granulocytes, platelets, lymphocytes, and red cells was evaluated in 33 babies who received granulocyte transfusion because of neonatal sepsis. Nine age-matched babies were examined as control. A first group of 19 infants was examined only once between 6 and 23 months of age. Alloantibodies were searched by the following serologic methods: standard techniques for red cell antibodies; lymphocytotoxicity test; agglutination and immunofluorescence tests on granulocytes and platelets. No antibodies were demonstrated. The immunologic profile was investigated by determining the Ig levels, the percentage of E rosette-forming cells, and the lymphocyte blastic response to phytohemagglutinin and concanavalin A. Granulocyte function was studied by phagocytosis and killing of Candida. No significant differences were observed between treated and control babies. In a second group of 14 infants the occurrence of early immunization within 3 to 9 weeks after the last transfusion was investigated. No evidence of early immunization was found. The present data suggest that following neonatal granulocyte transfusion the risk of adverse immune reactions should be low.

Interleukin 6 in neonates with early and late onset infection.

OBJECTIVE: To assess the utility of determining interleukin 6 (IL-6) concentrations for diagnosing early (< or = 48 h of life) and late onset infection in a neonatal intensive care setting. METHODS: We measured serum IL-6 values in five groups of neonates on both postnatal Days 1 and 2 (early sampling): Group 1, patients with clinical and microbiologic evidence of early onset infection; Group 2, patients with negative body fluid cultures but strong evidence of infection (clinical septicemia); Group 3, patients without clinical and microbiologic evidence of infection; Group 4, patients in whom infection could be neither confirmed nor excluded; and Group 5, healthy neonates with a normal postnatal course. We also measured IL-6 values in older neonates who during their hospital stay developed systemic infection (late sampling). Three controls matched for duration of hospital stay and birth date were chosen for each patient. RESULTS: On postnatal Day 1 IL-6 values were elevated in all four patient groups compared with those in healthy neonates (P < 0.05 by analysis of variance (ANOVA)). There were no significant differences found among patient groups. On postnatal Day 2 IL-6 concentrations were persistently elevated in Groups 1 and 2 compared with values from those in Group 3, Group 4 and healthy controls (P < 0.01). At this time no significant differences in IL-6 values were found between uninfected symptomatic patients (Group 3), patients with uncertain findings (Group 4) and healthy controls. IL-6 concentrations were significantly higher in patients with late onset infection at presentation than in the patient controls (P < 0.0001) and returned to low values in those who recovered from infection. CONCLUSIONS: There are differences in the serum concentrations of IL-6 that can be helpful in detecting early and late onset infection in preterm and term neonates. During the first 48 h of life serial IL-6 determinations are necessary so as not to overdiagnose infection in a neonatal intensive care setting.

Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies.

OBJECTIVE: To compare maternal and perinatal outcomes in twin pregnancies conceived via assisted reproductive techniques (ART) compared with spontaneous twin pregnancies. STUDY DESIGN: This retrospective study examined 345 dichorionic, di-amniotic twin pregnancies (207 conceived spontaneously and 138 conceived via ART), delivered between January 2007 and June 2011 at the San Pietro Fatebenefratelli Hospital, Rome, a tertiary medical centre. Maternal and perinatal outcomes were compared. A multiple logistic regression analysis was performed to calculate risk estimates as odds ratios (OR) adjusted for maternal age, parity and systemic diseases. Patient data were obtained from a computerized database and analyzed using Statistical Package for the Social Sciences Version 17. RESULTS: Gestational age and birth weight were lower in the ART group, and preterm delivery, gestational diabetes and placental abruption were higher in the ART group compared with the spontaneous conception group. The incidence rates of respiratory complications, patent ductus arteriosus and admission to the neonatal intensive care unit were higher among ART newborns. Length of hospital stay for mothers and newborns was longer in the ART group. No differences in mode of delivery, Apgar score at 5min, congenital anomalies, perinatal mortality, and other considered pregnancy and neonatal complications were found between the two groups. Multivariate analysis adjusted for maternal age, parity and systemic diseases revealed that only the rates of placental abruption [OR 7.45, 95% confidence interval (CI) 2.05-26.98] and patent ductus arteriosus (OR 3.39, 95% CI 1.01-11.46) were significantly higher for the ART group. CONCLUSIONS: Twin pregnancies conceived via ART are at greater risk of poorer outcomes than spontaneous twin pregnancies. This may be related to the type of conception and specific negative features of subfertile patients undergoing infertility treatment.

Blood transfusion therapy in the newborn.

This review deals with the various indications, the choice of blood products and the main aspects of their administration for transfusing neonates. Some special problems peculiar to neonatal age, that both neonatologists and blood transfusion services have to take into account, are emphasized. Exchange transfusion in the procedure most frequently used in blood transfusion therapy of neonatal hyperbilirubinaemia of various aetiology, severe anaemia and hyperviscosity due to polycythaemia. The procedure also represents a rational therapeutic approach in the bleeding thrombocytopenic newborn. More recently exchange transfusion has been utilized in the management of DIC, RDS and sepsis. Besides its advantages, metabolic, haemorrhagic and cardiac hazards of this "massive transfusion" are considered. Just as at any other age, the red cell preparation is the blood component most frequently utilized in the transfusion therapy of the neonate, considering not only the treatment of anaemia without hypovolaemic shock, but also the cases of iatrogenic blood loss, a common problem in the high risk neonatal intensive care unit. As transfusion of small increments of blood may often be required for the sick neonate and premature infant, different methods to cope with such conditions are discussed.

A rapid method for the separation of functional lymphoid cell populations of human and animal origin on PVP-silica (Percoll) density gradients.

Subclasses of lymphocytes can be separated on gradients of non-toxic polyvinylpyrrolidone-coated colloidal silica (Percoll) by virtue of differential densities. Such gradients can yield functionally active lymphocyte populations after brief centrifugation. Gradients can be generated in a discontinuous step fashion and centrifuged in standard table-top laboratory centrifuges or as self-generating gradients during ultracentrifugation. The density medium has low viscosity and can be made isotonic for virtually any use. Gradients have proved useful in both human and experimental animal studies, and high percentage yields allow for separations from small cell numbers. Methods are described for separation of whole blood and lymphoid subpopuctions. The cytoxic capability of various density fractions was evaluated for mixed lymphocyte culture-induced allogeneic killing and spontaneous, so-called "natural" killer cell activity. The lower density associated with blast transformation allows for significant enrichments of stimulated cells from in vitro cultures. Higher thymidine incorporation, restimualtion in mixed lymphocyte reactions, and greater cytotoxic capacity are associated with these "blast" fractions.

Anti-HIV 1 antibodies prevalence in parturients through newborn testing: results of the Italian anonymous serosurvey. The Italian Collaborative Study Group of HIV Prevalence in Newborns.

A prevalence assessment of HIV infection among parturients was performed in order to estimate the future incidence of pediatric AIDS cases and obtain data on the trend of the infection in Italy. Consecutive whole blood samples from newborns collected on filter paper from all regions of Italy (October-December 1990) for routine metabolic screenings, were anonymously examined for HIV-1 antibodies by an ELISA technique. Positive results were confirmed by Western blot. Among 97,658 blood samples tested, 121 (0.124%, 95% confidence interval Poisson distribution 0.103-0.148) were positive. A high prevalence of HIV infection (> 0.2%) was observed in four regions from North and Central Italy while, in some regions in the South, the seroprevalence was ten times lower. In the Lazio Region, namely in Rome, 5 inner-city hospitals with a particularly high prevalence of HIV infection were identified. Assuming that the prevalence of HIV infection observed in the population in this study may reflect the infection rate in the total population of childbearing women, we estimate that approximately 700 newborn babies were delivered from HIV-positive mothers in Italy during 1990. The identification of high prevalence areas could allow for the development of "targeted" testing programs to plan and provide adequate counselling and care of HIV-infected women and their infants.

Off-label and non-classical prescriptions of antipsychotic agents in ordinary in-patient practice.

OBJECTIVE: To estimate the proportion of off-label prescriptions of antipsychotics (APs) in ordinary in-patient practice. METHOD: From the South-Verona Psychiatric Case Register all admissions to the in-patient unit during 2001-02 were extracted. Prescriptions of APs were defined off-label when dispensed outside the licensed indications. In addition, the proportion of "non-classical prescriptions" was calculated. RESULTS: During the 2 years surveyed AP agents were prescribed in 311 cases. Nearly 50% of second-generation AP prescriptions were for an off-label indication. In contrast, <15% of first-generation AP prescriptions were for an off-label indication. About 30% of first- and second-generation agents were prescribed for a non-classical indication. CONCLUSION: Approved labels for second-generation AP agents cover a much narrower range of indications than any of the first-generation agents, and this explains the higher proportion of off-label prescriptions. In contrast, the everyday use of first- and second-generation APs cover a similar range of clinical indications.

Diffusing capacity for carbon monoxide in children with type 1 diabetes.

AIMS/HYPOTHESIS: Few data are available on lung dysfunction in children with diabetes. We studied the association of pulmonary function variables (flows, volumes and alveolar capillary diffusion) with disease-related variables in children with type 1 diabetes mellitus. METHODS: We studied 39 children with type 1 diabetes (mean age 10.9+/-2.6 years, disease duration 3.6+/-2.4 years, insulin.kg(-1).day(-1) 0.77+/-0.31) and 30 healthy control children (mean age 10.4+/-3.0 years). Pulmonary function tests included spirometry, N(2) wash-out and the single-breath diffusing capacity for carbon monoxide (DL(CO)) corrected for the alveolar volume (DL(CO)/V(A)). Glycaemic control was assessed on the basis of HbA(1)c, with HbA(1)c values of 8% or less considered to indicate good glycaemic control, and HbA(1)c values of 8% or more considered to indicate poor control. RESULTS: Children with poor glycaemic control had comparable percentage values for predicted flows and volumes but lower DL(CO)/V(A) values than children with good glycaemic control and healthy control children (86.7+/-12.6 vs 99.8+/-18.4 and 102.0+/-15.7; p<0.05). The predicted DL(CO)/V(A) percentages correlated with HbA(1)c levels (r=-0.39, p=0.013). A multiple regression analysis (stepwise model) controlling for HbA(1)c levels and other disease-related variables (age of disease onset, disease duration, daily insulin dose/kg, sex) identified HbA(1)c levels as the sole predictor of DL(CO)/V(A) in percent. CONCLUSIONS/INTERPRETATION: In children with type 1 diabetes, the diffusing capacity diminishes early in childhood and is associated with poor metabolic control. Although low DL(CO)/V(A) levels in these children probably reflect pulmonary microangiopathy induced by type 1 diabetes, other factors presumably influencing CO diffusion capacity measurements (e.g. a left shift in HbA(1)c resulting in high O(2) binding and low CO binding) could explain the apparent capillary and alveolar basal membrane dysfunction.

[Potentials and limitations of viscometry in hemorheological studies]. / Potenzialità e limiti della viscosimetria negli studi emoreologici.

The problems of viscometric studies are discussed in depth on the basis of the most recent advances in hemorheology. We present here our contribution to the solution of numerous methodological problems. Particular emphasis was set on the problem of optimization and standardization of viscometric techniques for the study of erythrocyte deformation and aggregation.

Temporal and geographical trends of anti-HIV-1 antibodies screening among newborns in Italy, 1990-1993. Italian Collaborative Study Group for HIV Prevalence in Newborns.

To describe the dynamic of HIV-1 prevalence in Italian childbearing women and to estimate the future incidence of pediatric AIDS due to vertical transmission, dried-blood specimens collected from a consecutive sample of newborns in all Italian regions were examined for the presence of anti-HIV-1 antibodies (HIV-Ab) after the routine neonatal screening program was completed. Of 555,722 blood samples collected and examined for HIV-Ab between 1990 and 1993, 550 (0.099%) were positive. Nationwide, the HIV seroprevalence decreased between 1990 and 1992 (0.124% in 1990, 0.100% in 1991, 0.085% in 1992), and increased, as compared with that in the previous year, in 1993 (0.096%). In an univariate analysis, HIV seroprevalence was positively was positively associated with being born in regions having higher AIDS cumulative incidence and in metropolitan areas, but negatively associated with year of delivery. In a multiple logistic regression analysis, only the AIDS cumulative incidence level of the delivery area and being born in a metropolitan area remained independently associated with HIV seroprevalence. Our results show significant geographical variation in the spread of HIV infection among childbearing women in Italy and provide useful indications to target prevention and care strategies for HIV-infected women and their children and to estimate the potential impact of implementing programs aimed at preventing vertical transmission of HIV infection.

Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates.

We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

Antibody production in infants born to HIV-1-infected mothers.

Naturally occurring antibodies to polysaccharide antigens of pathogens commonly isolated from HIV-1-infected subjects were analyzed in serially collected sera of children born to seropositive mothers. Purified polysaccharides from type 14 Streptococcus pneumoniae, group C Neisseria meningitidis, type b Haemophilus influenzae, glucomannoprotein from Candida albicans and diphtheria toxoid antigens were used in an ELISA test to assess antibody levels. A significant rise of anti-pneumococcus antibody titres was noticed both in HIV-1-infected and in non-HIV-1-infected children aged 18 months or more. Anti-C. albicans and anti-group C N. meningitidis antibodies were elevated only in HIV-1-infected children older than 12 months. Anti-type b H. influenzae antibodies remained at low titres in both groups. Anti-diphtheria toxoid antibodies, analyzed as a model of humoral response to a protein antigen, were similar in both groups of HIV-1-infected and noninfected children.

Prenatal exclusion of purine nucleoside phosphorylase deficiency.

We report on the prenatal exclusion of purine nucleoside phosphorylase (PNP) deficiency in a fetus whose parents were known to be heterozygotes for the enzyme defect. Prenatal investigation was performed in the 16th week of gestation on amniotic fluid and cultured amnion cells using sensitive techniques. The results suggested that the fetus was either normal or a heterozygote. PNP activity in cord red cells confirmed the heterozygous status of the baby.

Clonal dominance among T-lymphocyte infiltrates in arthritis.

Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) beta-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders.