Efficacy of recombinant human granulocyte colony-stimulating factor in a murine model of pneumococcal pneumonia: effects of lung inflammation and timing of treatment

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a murine model of pneumococcal pneumonia was examined. Intranasal inoculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (low inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly improved survival when initiated 24 h or 10 min before, but not when initiated 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increased circulating neutrophil count 24, 48, and 72 h after infection. In contrast, rhG-CSF did not improve survival of animals infected with the high inoculum and did not increase MPO activity or neutrophil count in blood over those of sham-treated controls. These data strongly suggest that the severe inflammatory response typically observed in pneumococcal pneumonia recruits a maximum number of neutrophils in the lungs and thus masks the beneficial effect of rhG-CSF.     

Rituximab: the first monoclonal antibody approved for the treatment of lymphoma

Rituximab, a genetically engineered monoclonal chimeric antibody, targets the CD20 antigen expressed on B cells. It was approved by the US Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma (LG/F NHL), and by the European Agency for the Evaluation of Medicinal Products on June 2, 1998, for therapy of patients with Stage III/IV, follicular, chemoresistant or relapsed NHL. Eight Phase II or II clinical trials in LG/F NHL patients have been completed: five single-agent studies and three combination studies. Rituximab has a favorable safety profile: most adverse events (AEs) are Grade 1 or 2, and the frequency of AEs decrease with subsequent infusions. AEs in the combination studies are consistent with those seen with individual agents. For evaluable patients in the single-agent studies, overall response rates (ORR) ranged from 40% to 60%, median duration of response (DR) ranged from 5.9 to 15.0+ months, and median time to progression (TTP) ranged from 8.1 to 19.4+ months. For evaluable patients in the combination studies, the ORR ranged from 45% to 100%, median DR ranged from 11.7+ to 39.1+ months, and median TTP ranged from 12.9+ to 40.5+ months. Studies in intermediate- and high-grade NHL are ongoing. Long-term development plans include evaluating the safety and efficacy of rituximab in various types of lymphoma and in combination with other lymphoma regimens. Future studies may explore ways to increase rituximab efficacy by upregulating CD20 or increasing effector function with different cytokines.     

Rationale and Design of the FREQUENCY Study: The Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology

Objective

Prenatal detection of congenital heart diseases (CHD) decreases morbidity and cost. To improve detections rates, most physicians refer pregnant women with high-risk pregnancies to fetal cardiologists even when there is no suspicion of CHD at the second trimester screening. This paper presents the rationale and detailed method of the Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology (FREQUENCY) study. The overall objective is to assess the impact of second trimester ultrasound screening (U/S) and referral pattern in fetal cardiology on detection rates, health care costs, and resource utilization, as well as perinatal morbidity and mortality.

Occurrence and properties of fetal intestinal glycosidases (disaccharidases) in human amniotic fluid.

alpha-Glucosidase, beta-glucosidase and beta-galactosidase were studied in cell-free amniotic fluid samples using corresponding 4-methylumbelliferyl-glycosides and a series of disaccharides (maltose, sucrose, trehalose, turanose, cellobiose, gentiobiose and lactose) as substrates. The glycosidases exhibited several properties of intestinal disaccharidases such as pH optimum between 5.2 and 6.4, more activity towards the disaccharides than the artificial substrates, tight association of the activities with sedimentable complexes and beta-glucosidase and beta-galactosidase activities exerted by a single catalytic site. With the disaccharides as substrates, the amniotic fluid glycosidase activities were well correlated to those reported in the literature for fetal intestine of corresponding gestational ages. The presence of intestinal disaccharidases in amniotic fluid indicates that the fetal intestine contributes to the protein and enzymes of amniotic fluid.     

Reproductive and morphological effects of halogenated dimethyl bipyrroles on captive American kestrels (Falco sparverius)

Sixty-four adult captive American kestrels (Falco sparverius) were exposed to a dietary source of halogenated dimethyl bipyrroles (HDBPs), a group of organohalogens proposed to have a natural origin. Adult kestrels were assigned to four treatment groups that were administered a different dose of HDBPs [high, 140 microg/(bird x d); medium, 4.3 microg/(bird x d); low, 0.13 microg/(bird x d); control, 0 microg/(bird x d)]. Exposure began prior to pairing and continued during breeding until approximately 28 d after hatching of the final eggs. Juvenile and adult kestrels accumulated HDBPs in carcass tissue, plasma, and liver. In addition, HDBPs were transferred to yolks during egg development. Low dietary absorption efficiencies (0.011-0.029) indicated that HDBPs were effectively cleared from kestrels either from increased elimination, metabolism, or a combination of the two processes. Reproductive and morphological endpoints examined for HDBP-induced changes included egg volume, egg mass, eggshell thickness, egg fertility, clutch size, liver and whole body mass, antebrachium, central retrice, tarsus, ninth primary, and wing cord lengths. Few statistically significant dose-dependent effects were observed. Hepatic tissue samples from selected individuals underwent histomorphological evaluation. Although the hepatic function was not evaluated specifically in these birds, no clinical signs suggestive of liver disease or gross hepatic anomalies were observed. Only minor histomorphological changes were detected in the hepatic tissue. The lack of serious effects suggests that HDBPs are not an acute reproductive threat to avian populations.     

Vitamin A concentration in umbilical cord blood of infants from three separate regions of the province of Québec (Canada)

BACKGROUND: Inuit women from Northern Québec have been shown to consume inadequate quantities of vitamin A. This study was conducted to evaluate the prevalence of blood vitamin A deficiency in newborns from 3 distinct populations of the province of Québec. METHODS: 594 newborns were included in this study (375 Inuit newborns from northern Québec (Nunavik), 107 Caucasian and Native newborns from the Lower Northern Shore of the Saint-Lawrence River (LNS) and 112 newborns from Southern Québec where clinical vitamin A deficiency is uncommon). Mothers were recruited at delivery and vitamin A (retinol) was analyzed from umbilical cord blood samples by reversed-phase high-pressure liquid chromatography. RESULTS: Nunavik and LNS newborns had significantly lower mean vitamin A concentrations in cord blood compared to Southern Québec participants (15.7 microg/dL, 16.8 microg/dL and 20.4 microg/dL respectively). The differences observed were similar when adjusted for sex and birthweight. Results also showed that 8.5% of Nunavik newborns and 12.2% of LNS newborns were below 10.0 microg/dL, a level thought to be indicative of blood vitamin A deficiency in neonates. CONCLUSION: These data suggest that a carefully planned vitamin A supplementation program during pregnancy in Nunavik and LNS might be indicated to promote healthy infant development.     

Monitoring of umbilical cord blood lead levels and sources assessment among the Inuit

Analyses completed on samples collected between 1993 and 1996 showed that about 7% of 475 Inuit newborns from northern Quebec (Canada) had a cord blood lead concentration equal to or greater than 0.48 micromol/l, an intervention level adopted by many governmental agencies. A comparison between the cord blood lead isotope ratios of Inuit and southern Quebec newborns showed that lead sources for these populations were different. Our investigation suggests that lead shots used for game hunting were an important source of lead exposure in the Inuit population. A cohort study conducted in three Inuit communities shows a significant decrease of cord blood lead concentrations after a public health intervention to reduce the use of lead shot. Lead shot ammunition can be a major and preventable source of human exposure to lead.     

Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: their characterization and delineation of defects in pregnancies at risk.

During a follow-up study of 19,790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.     

Effect of amino acid composition of parenteral solutions on nitrogen retention and metabolic response in very-low-birth weight infants

To evaluate the influence of amino acid preparations on the metabolic response of parenterally fed immature newborn infants, nitrogen retention and plasma amino acid concentrations were compared in very-low-birth-weight infants given two parenteral regimens differing only by the composition of the infused amino acids (Travasol 10% blend B and Vamin 7%). The intakes of fluid, nitrogen, and calories were comparable. The nitrogen retention was 72% +/- 7% with Vamin and 65% +/- 6% with Travasol. The differences in plasma amino acid concentrations were consistent with the composition of the amino acid solutions. During the infusion of Vamin the increased intake of aromatic amino acids resulted in high plasma levels of tyrosine (256 +/- 233 mumol/L, range 67 to 894 mumol/L). The infusion of Travasol resulted in high plasma levels of methionine (114 +/- 39 mumol/L, range 53 to 260 mumol/L) and an elevated load of glycine, which was accompanied by an abnormally high urinary loss of this amino acid. Despite these metabolic imbalances, the growth rate over the whole study was adequate. These results emphasize the importance of the composition of amino acid solutions on the metabolic response of the very immature preterm infant.