Significance of a false-positive trisomy 18 multiple-marker screening test

We report our results in 24 children with malignant primary bone tumours of the distal femur treated with a Stanmore extendible endoprosthesis (SEER). This consists of a femoral component that can be lengthened, a constrained knee and an uncemented sliding tibial component which crosses the proximal tibial physeal plate perpendicularly. The average age of the patients at diagnosis was ten years and the mean follow-up was 4.7 years (2.5 to 7.9). The mean growth of the affected tibia was 76% (18 to 136) and of the fibula 83% (15 to 750) of the growth of the unaffected limb. Measurement of growth arrest lines showed that the mean growth of the proximal tibial physis on the affected side was 69% (43 to 100) of that of the normal side. The great variability in the growth of the physis cannot yet be explained.     

Mechanisms of in vivo anti-neuroblastoma activity of human natural IgM

Normal human sera of healthy adults contain natural IgM antibodies which are cytotoxic for human neuroblastoma cells. In this study, we evaluated the anti-neuroblastoma activity of these natural IgM antibodies in nude rats bearing solid human neuroblastoma tumours. A single intravenous (i.v.) injection of purified cytotoxic IgM led to uptake of IgM in the tumours with massive perivascular complement activation and accumulation of neutrophil granulocytes after 24 h. Five consecutive i.v. injections of purified cytotoxic IgM into neuroblastoma-bearing animals resulted in complete growth arrest of even large established solid tumours which lasted for several weeks after discontinuation of the injections, whereas tumours of control animals continued to grow exponentially during the observation period. These studies suggest that natural anti-neuroblastoma IgM may have a potential as a novel therapeutic modality in the treatment of human neuroblastoma.     

Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL

PURPOSE: We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS: Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS: There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION: Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.     

Toward targets for initiation of chronic dialysis

OBJECTIVES: To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients. DESIGN: This cross-sectional study was a prospective observational design meant to study each patient once. SETTING: The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri. PATIENTS: Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD. RESULTS: In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion. CONCLUSIONS: The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.     

A third secreted protein that is encoded by the enteropathogenic Escherichia coli pathogenicity island is required for transduction of signals and for attaching and effacing activities in host cells

Enteropathogenic Escherichia coli strains are able to signal host cells, cause dramatic cytoskeletal rearrangements, and adhere intimately to the cell surface in a process known as the attaching and effacing effect. A pathogenicity island of 35 kb known as the locus of enterocyte effacement (LEE) is necessary and sufficient for this effect. The LEE encodes an outer membrane adhesin called intimin, a type III secretion apparatus, and the EspA and EspB secreted proteins. The DNA sequence of the region between espA and espB revealed a new gene, espD. The product of espD was demonstrated by using a T7 expression system. We constructed a nonpolar mutation in espD and found that the mutant is incapable of the signal transduction events that lead to activation of the putative intimin receptor in host cells and that the mutant fails to induce the attaching and effacing effect. These phenotypes were restored to the mutant by complementation with a plasmid containing the cloned espD locus. We demonstrated by immunoblotting and microsequencing that the EspD protein is secreted via the type III apparatus. Thus, we describe a novel locus encoding a secreted protein that is required for attaching and effacing activity.     

Prenatal care utilization in New York City: comparison of measures and assessment of their significance for urban health

Short-term exposure to the air pollutant ozone results in severe injury to the nares, trachea, and centriacinus. Long-term exposure however, leads to a state of tolerance that is characterized by remodeling in the centriacinar airways and markedly reduced cell necrosis and inflammation. This remodeling consists of hypertrophy and hyperplasia of Clara cells with a 2- to 5-fold increase in the intracellular content of the major protein synthesized by the Clara cell, Clara cell secretory protein (CCSP). Previous in vitro studies suggest that CCSP may moderate inflammation and bind reactive cytotoxicants. This study tested whether acute and chronic exposure to ozone alters the normal level of expression of the CCSP gene. Rats were exposed to ozone, 1 ppm 8 h nightly, for up to 90 days. Immunohistochemistry demonstrated repopulation of the alveolar ducts with CCSP positive Clara cells and an increase in the intensity of immunoreactive CCSP within Clara cells. The results showed that (1) CCSP mRNA expression, GAPDH, and beta-actin do not change as a result of ozone injury, (2) mRNA levels are more variable as a result of ozone injury and (3) CCSP mRNA expression increases with age.     

Behavioral effects of prematurity

This report reviews the evidence for an increased incidence of behavior and social problems in infants and children born prematurely. The contribution of biological and social factors to the development of behavior problems in this population is also examined. The available evidence indicates that preterms more often than full-terms exhibit negative temperament characteristics, symptoms of Attention-Deficit Hyperactivity Disorder, and lower levels of social competence. The risk for these problems appears to be limited to those infants with a birth weight of less than 1,500 g. Adverse social conditions also impact the expression of these problems. Preterms do not appear to be at as much risk for emotional or conduct problems or abnormal attachment to their mothers. Both the experience of a preterm birth and the characteristics of the infant can alter the perceptions and behavior of parents. Appropriate interventions should involve the child, the parents, and the school.     

Protective effects of interferon-gamma in intraocular herpes simplex type 1 infection do not depend on major histocompatibility complex class I or class II expression

Intraocular infection with herpes simplex virus type I strain F (HSV-1) induces bilateral retinitis, the expression of both MHC class I and II molecules and activation of CD4 and CD8 cells. To investigate the role of MHC upregulation in IFN-gamma mediated antiviral effects in intraocular infection with HSV-1, we infected MHC deficient mice and mice with an additional ectopic site of IFN-gamma production in their retina (rho gamma) intravitreally with HSV-1 into one eye. Protective effects of IFN-gamma in intraocular HSV-1 infection were notable as sparing of the contralateral non-inoculated eye from retinitis, and were not dependent on MHC class I and class II expression, thus limiting the importance of MHC expression for the outcome of viral infection in vivo.