Genotoxic potential associated with low levels of the Fusarium mycotoxins nivalenol and fusarenon X in a human intestinal cell line.

This study aims to assess the genotoxic potential of nivalenol (NIV) and fusarenon X (FusX), produced by various Fusarium on cereals. Toxins were applied in time and dose-dependent experiments to the human enterocyte-like Caco-2 cell-line, both in dividing (undifferentiated) and in 10-12 days post-confluent cells (differentiated). Genotoxicity was evaluated through the alkaline Comet assay in a concentration range defined for each toxin as below the cytotoxicity threshold IC(10), determined by the MTS and the neutral red assays, to prevent false positive results because of DNA damage stemming from necrosis. Thus, genotoxicity was explored in the sub-cytotoxic 0-0.5 microM and 0-0.05 microM ranges respectively for NIV and FusX as the latter was found about 10-fold more cytotoxic than NIV. For both toxins, a 3h exposure did not cause any DNA damage, unlike after 24 and 72 h exposure in post confluent Caco-2 cells where DNA damage was significantly observed with a dose-dependent relationship. In dividing cells, only FusX increases DNA strand breaks in the 0.01-0.05 microM range after 72 h. These results demonstrated the existence of a genotoxic potential for NIV and FusX at low exposure levels and could contribute to the risk assessment process of these toxins that are of growing concern.

A novel strategy based on genomics and specific PCR reveals how a multidrug-resistant Mycobacterium tuberculosis strain became prevalent in Equatorial Guinea 15 years after its emergence.

OBJECTIVE: Molecular epidemiology techniques in tuberculosis (TB) can identify high-risk strains that are actively transmitted. We aimed to implement a novel strategy to optimize the identification and control of multidrug-resistant (MDR) TB in a specific population. METHODS: We developed a strain-specific PCR tailored from whole genome sequencing (WGS) data to track a specific MDR prevalent strain in Equatorial Guinea (EG-MDR). RESULTS: The PCR was applied prospectively on remnants of GeneXpert reaction mixtures owing to the lack of culture facilities in Equatorial Guinea. In 147 (93%) of 158 cases, we were able to differentiate between infection by the EG-MDR strain or by any other strain and found that 44% of all rifampicin-resistant TB cases were infected by EG-MDR. We also analysed 93 isolates obtained from Equatorial Guinea 15 years ago, before MDR-TB had become the problem it is today. We found that two of the scarce historical MDR cases were infected by EG-MDR. WGS revealed low variability-six single nucleotide polymorphisms acquired by this strain over 15 years-likely because of the lack in the country of a specific program to treat MDR-TB. CONCLUSIONS: Our novel strategy, which integrated WGS analysis and strain-specific PCRs, represents a low-cost, rapid and transferable strategy that allowed a prospective efficient survey and fast historical analysis of MDR-TB in a population.

Diverse roentgenographic manifestations of the rare pulmonary involvement in myeloma.

Roentgenographic manifestations of two cases of pulmonary involvement with myeloma were presented. One showed a nodular mass lesion extending from an extramedullary mediastinal plasmacytoma into the lung parenchyma while the other showed diffuse reticulonodular infiltrate by myeloma cells in association with alveolar septal amyloidosis. These two cases demonstrate the extreme variability of pulmonary involvement by myeloma, which can mimic a solitary tumor or an inflammatory infiltrate.

Preferences of pregnant women and physicians for 2 strategies for prevention of early-onset group B streptococcal sepsis in neonates.

OBJECTIVES: To assess preferences of pregnant women, pediatricians, and obstetricians for the policies of the American College of Obstetrics and Gynecology (ACOG) and American Academy of Pediatrics (AAP) for reducing the incidence of neonatal group B streptococcal (GBS) sepsis. DESIGN: An interactive interview using a computer-based decision-making model (analytic hierarchy process) and a self-administered survey assessing the interview process. SETTING: An obstetric clinic at a university center and offices of practicing physicians from the Birmingham, Ala, area. PARTICIPANTS: Ninety-two pregnant women selected by a systematic sampling technique and 40 pediatricians and 40 obstetricians selected randomly. MAIN OUTCOME MEASURE: Ranking of the ACOG and AAP policies and the 5 criteria on which the decision was based: risk of infection to an infant, knowledge of maternal GBS status, risk of anaphylaxis to mother, diagnostic tests received by healthy infants, and cost. Satisfaction with the interview process also was measured. RESULTS: Eighty-three women (90%), 40 pediatricians, and 40 obstetricians (100%) provided responses suitable for analysis. Sixty-seven pregnant women (81%), 26 pediatricians (65%), and 6 obstetricians (15%) preferred the AAP strategy. The ACOG policy was the preferred strategy by 34 (85%) obstetricians. The 3 groups ranked risk of infection in an infant as the most important criterion in their decisions. Ranks for the other criteria differed among the 3 groups. Women ranked knowledge of maternal GBS status more important than did pediatricians and obstetricians. Thirty obstetricians (75%), 35 pediatricians (87.5%), and 72 pregnant women (86.7%) liked the interview. Seventy-three women (88%), 29 pediatricians (72.5%), and 17 obstetricians (42.5%) thought physicians should use this type of interview to assist in managing patients. CONCLUSIONS: Pregnant women, pediatricians, and obstetricians had different priorities when making a decision about GBS policies. These differences led obstetricians to prefer a different policy than that of pediatricians and pregnant women. Obstetricians were less likely to endorse the use of this decision-making technique in their practice than were patients and pediatricians.

Impact of maternal group B streptococcal screening on pediatric management in full-term newborns.

BACKGROUND: The American Academy of Pediatrics strategy to prevent early-onset neonatal sepsis with group B streptococcus (GBS) relies on maternal antepartum GBS cultures, while the American College of Obstetrics and Gynecology strategy does not. OBJECTIVE: To evaluate the impact of the 2 strategies on the care of asymptomatic full-term newborns. DESIGN/SETTING: Self-administered survey mailed to a national random sample of US pediatricians who were members of the American Academy of Pediatrics. PARTICIPANTS: A total of 461 members of the American Academy of Pediatrics who routinely care for newborns. MAIN OUTCOME MEASURE: Self-report of diagnostic and treatment strategies for asymptomatic full-term newborns who were born under different clinical scenarios. Maternal risk factors, antepartum maternal GBS screening status, and maternal treatment with intrapartum antibiotics were varied across the scenarios. RESULTS: Pediatricians treating asymptomatic full-term newborns born to risk factor-negative mothers reported ordering tests (63.3% in GBS-positive cases vs 6.7% with GBS unknown; P = .001) and antibiotics (21.5% in GBS-positive cases vs 0.9% with GBS unknown; P = .001) more frequently when presented with a positive maternal GBS screening result. Maternal intrapartum treatment had little impact on pediatric practice when risk factors were absent. In risk factor-positive mothers, pediatricians reported an increase in their antibiotic usage in response to a positive maternal GBS screen (61.8% in GBS-positive cases vs 36.9% with GBS unknown; P = .001). In risk factor-positive mothers with unknown results of GBS screening, use of intrapartum antibiotics increased the number of pediatricians who reported that they would prescribe antibiotic therapy. CONCLUSIONS: Obstetrical strategies to decrease the risk of neonatal GBS sepsis increase pediatric services provided to full-term healthy newborns. This increase in services by pediatric practices is likely to be greater with the screening-based strategy recommended by the American Academy of Pediatrics.

The pediatric costs of strategies for minimizing the risk of early-onset group B streptococcal disease.

OBJECTIVE: To estimate the pediatric costs associated with the Centers for Disease Control and Prevention (CDC) guidelines for the management of infants born to mothers receiving intrapartum antimicrobial prophylaxis for prevention of early-onset group B streptococcal disease. METHODS: For an annual United States birth cohort of 3.95 million infants, we estimated the cost of pediatric care provided to full-term asymptomatic infants when pediatricians followed the CDC algorithm for the management of infants exposed to intrapartum antimicrobial prophylaxis under culture-based and risk factor-based maternal care approaches. We calculated the relative contribution of pediatric costs to the total costs of preventing a case of early-onset group B streptococcal sepsis. RESULTS: Total pediatric costs were $41 million for a culture-based approach and $33 million for a risk factor-based approach. Hospital and physician costs accounted for more than 78% of this total. The majority (over 95%) of the pediatric costs were associated with vaginal deliveries. Incorporating pediatric costs into previous cost-effectiveness analyses increased the cost per sepsis case averted by as much as 51% for culture-based strategies and by as much as 112% for risk factor-based strategies. Pediatric costs varied with the average length of stay for full-term infants and with the average cost of a hospital day. CONCLUSION: Substantial pediatric costs are associated with the implementation of an obstetric strategy for minimizing the risk of early-onset group B streptococcal disease. Such costs should be included in future cost-effectiveness analyses of different strategies for minimizing the risk of group B streptococcal disease in newborns.

Influence of acid-base status at birth and Apgar scores on survival in 500-1000-g infants.

OBJECTIVE: To evaluate the influence of acid-base status at birth and Apgar scores on survival in very low birth weight infants. METHODS: We evaluated 1073 infants born alive and weighing 500-1000 g during 1979-1991; 658 had umbilical artery gas values examined. Apgar scores were assigned at 1 and 5 minutes after birth. Umbilical artery blood samples were collected at delivery for pH, carbon dioxide pressure (PCO2), and bicarbonate. Infants were grouped at 23-24, 25-26, 27-28, and 29 weeks or more. Using survival as the dependent variable, multiple logistic regression analyses were performed controlling for gestational age, birth weight, plurality, antenatal glucocorticoid use, mode of delivery, and year of birth, as well as for Apgar scores and cord blood gases. RESULTS: In every gestational age grouping, compared with infants with a pH lower than 7.05, survival was higher in infants with an umbilical artery pH of 7.05 or higher, significantly so at 27-28 weeks. There was no consistent relationship between umbilical artery PCO2 or bicarbonate and survival. However, with the exception of the 1-minute Apgar score at 23-24 weeks, the relationship of Apgar scores to survival was significant in all gestational age periods. Using multiple logistic regression analyses, the only significant relationships between any of the cord blood gases, Apgar scores, and mortality involved low 1-minute (odds ratio [OR] 2.7 [95% confidence interval (CI) 2.0-3.6]) and low 5-minute Apgar scores (OR 2.8 [95% CI 2.0-3.8]) and a bicarbonate less than 21 mEq/L (OR 1.6 [95% CI 1.1-2.4]). CONCLUSION: One- and 5-minute Apgar scores are better predictors of survival than umbilical artery blood gases in neonates weighing 500-1000 g at birth.

Behavioral and socioemotional competence problems of extremely low birth weight children.

OBJECTIVE: To examine behavioral and social-emotional problems in extremely low birth weight (ELBW) children and to assess factors associated with behavioral and social competency outcomes at 30 to 36 months adjusted age. STUDY DESIGN: A total of 696 ELBW (401 to 1000 g) children from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were included. Behavioral and social-emotional problems were assessed using the Brief Infant-Toddler Social and Emotional Assessment administered to parents. Unadjusted comparisons were performed between children with or without behavioral or social-emotional problems. Logistic regression was used to examine factors associated with behavioral outcomes. RESULT: Parents reported behavioral problems in 46.8%, deficits in social-emotional competence in 20.4% and having both behavioral and social-emotional competence problems in 15.4% of ELBW children. Characteristics associated with behavioral problems in logistic regression included female gender, lower household income and a Bayley Psychomotor Developmental Index (PDI)<70. Deficits in social competence were associated with Bayley Mental Developmental Index (MDI) and PDI scores<70 and Hispanic or Other races compared with White non-Hispanic. CONCLUSION: Half of the (51.9%) ELBW children showed behavioral or social-emotional competence problems at 30 months. Low socioeconomic status and low Bayley MDI and PDI scores were associated with behavioral and socioemotional difficulties.

[Experimental reproduction of lactic acidosis in the pony]. / Reproduction expérimentale de l'acidose lactique chez le poney.

One pony has been subjected to the intravenous injections of L-lactic acid. Two other ponies have been trained to intracaecal administration of L-lactic acid or sucrose. The obtained results show that: Intravenous injection of lactic acid increases the concentration of histamin and lactic acid, decreases the level of magnesium and reduces the pressure of carbon dioxide in the blood (the control animals and the treated animals) without the clinical symptoms of lactic acidosis. Intracaecal administration of lactic acid induces a high liberation of histamin in the caecum (the control animals and the treated animals), however, the level of histamin in the blood is not modified. Intracaecal administration of sucrose decreases pH and increases the concentration of lactic acid in the caecum, although, in this case, the accumulation of histamin in the caecum appears only in the non-fasting ponies, the starved animals, and the fed animals, which suggests the necessity of food's proteins for histamin synthesis.

Growth of adolescents who were born at extremely low birth weight without major disability.

OBJECTIVE: To compare growth between adolescents who were born at extremely low birth weight (ELBW, /=2500 g). DESIGN/METHODS: Cross-sectional design. Fifty-three ELBW and 53 NBW adolescents without a major neurodevelopmental disability were matched by sex, race, age, and socioeconomic status. Anthropometrics (z scores), bone age, body composition (Lunar DPX-L densitometry), and sexual maturity were assessed. ELBW adolescents were classified as being born small for gestational age (SGA) or not (NSGA). RESULTS: Subjects were 58.5% female, 43.4% black, and 56.6% white. The mean birth weight for ELBW subjects was 849 g and 3355 g for NBW subjects. The mean age was 14.85 years. On average, ELBW adolescents were 4.8 cm shorter and 9.1 kg lighter than NBW adolescents. ELBW adolescents had lower mean z scores for height (P <.0001), weight (P <.0001), and head circumference (P <.0001) than NBW adolescents. ELBW/SGA subjects had lower mean z scores for height (P <.0001) and weight (P =.001) than NBW subjects. Head circumference z scores were lower for the ELBW/SGA group than the ELBW/NSGA group or the NBW group (P =. 003). Sexual maturity and relative body composition were similar between groups. Bone age, measured in SD units, was more advanced in the ELBW group (0.86 vs. 0.42, P =.039). CONCLUSIONS: ELBW adolescents who survive without a major neurodevelopmental disability attain lower growth measurements compared with NBW adolescents but have similar sexual maturation and relative body composition.

Acid-base status at birth and subsequent neurosensory impairment in surviving 500 to 1000 gm infants.

OBJECTIVE: The purpose of this study was to assess, in infants born weighing < or = 1000 gm, if umbilical cord blood acid-base measures at birth are associated with an additional increase in neurosensory impairment. STUDY DESIGN: Of 289 surviving infants with a birth weight of 500 to 1000 gm born from 1979 to 1989, 219 had umbilical cord acid-base status measured at birth and were followed prospectively for > or = 1 year. Measures of neurologic impairment used in this study included mental retardation, cerebral palsy, and major neurosensory impairment. RESULTS: Gestational age was inversely associated with all neurosensory impairments and was a better predictor of subsequent impairment in this population than was birth weight. Very low umbilical cord pH values were also significantly related to adverse outcomes. There was also an inverse relationship between cord blood bicarbonate levels and major neurosensory impairment. The highly significant relationship between cord blood bicarbonate and pH values and the development of neurosensory impairments persisted in spite of adjustment for gestational age, birth weight, plurality, use of general anesthesia, maternal race, and presence of hypertension. CONCLUSION: An adverse acid-base status at birth is additive to the effect of gestational age in predicting neurosensory impairment in infants weighing < or = 1000 gm.