Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study

Introduction

The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities.

Methods

Fifty-eight preterm infants, gestational age 29?±?2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation.

Results

No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI.

Conclusion

DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.     

Modulated expression of WFDC1 during carcinogenesis and cellular senescence

Fibroblasts located adjacent to the tumor [cancer-associated fibroblasts (CAFs)] that constitute a large proportion of the cancer-associated stroma facilitate the transformation process. In this study, we compared the biological behavior of CAFs that were isolated from a prostate tumor to their normal-associated fibroblast (NAF) counterparts. CAFs formed more colonies when seeded at low cell density, exhibited a higher proliferation rate and were less prone to contact inhibition. In contrast to the general notion that high levels of alpha-smooth muscle actin serve as a marker for CAFs, we found that prostate CAFs express it at a lower level compared with prostate NAFs. Microarray analysis revealed a set of 161 genes that were altered in CAFs compared with NAFs. We focused on whey acidic protein four-disulfide core domain 1 (WFDC1), a known secreted protease inhibitor, and found it to be downregulated in the CAFs. WFDC1 expression was also dramatically downregulated in highly prolific mesenchymal cells and in various cancers including fibrosarcomas and in tumors of the lung, bladder and brain. Overexpression of WFDC1 inhibited the growth rate of the fibrosarcoma HT1080 cell line. Furthermore, WFDC1 level was upregulated in senescent fibroblasts. Taken together, our data suggest an important role for WFDC1 in inhibiting proliferation of both tumors and senescent cells. Finally, we suggest that the downregulation of WFDC1 might serve as a biomarker for cellular transformation.     

Engraftment of human blood malignancies to the turkey embryo: A robust new in vivo model

Xenografting of human blood malignancies to immunodeficient SCID mice is a powerful research tool. We evaluate here whether the immunodeficient turkey embryo can also serve as a xenograft host for human blood malignancies. Human leukemia, lymphoma and myeloma lines engrafted robustly into medullary and extramedullary tissues of turkey embryos as detected by PCR, FACS and histology in 8–10 days. Four of eleven patient AML samples also engrafted the bone marrow. Grafts of two lines responded to chemotherapy with doxorubicin. The turkey embryo therefore has the potential to be a complementary xenograft model for the study of human blood malignancies.     

Posttransfusion equilibration of hematocrit in hemodynamically stable neonates.

OBJECTIVE: To determine whether hematocrit obtained 15 mins after blood transfusion in hemodynamically stable neonates is significantly different from that obtained after 6 hrs. We hypothesized that the hematocrit stabilizes within the first 15 mins that follow a 3-hr blood transfusion in preterm infants. DESIGN: We prospectively studied 24 consecutive infants who received blood transfusion. Hematocrit was measured immediately before the transfusion and 15 mins and 6 hrs after the transfusion of 10 mL/kg body weight of sedimented red blood cells administered over 3 hrs. Hematocrit was measured by centrifugation of a capillary. RESULTS: There was a significant increase in hematocrit from pretransfusion values both at 15 mins and 6 hrs. The increase in hematocrit from the pretransfusion value was identical (11%) at both 15 mins and 6 hrs. CONCLUSION: The hematocrit obtained 15 mins after the end of a 3-hr blood transfusion in hemodynamically stable, anemic infants is indistinguishable from that obtained after 6 hrs in the same infants. Thus, if the increase of hematocrit is deemed insufficient at 15 mins after the transfusion, it is possible to complete the transfusion without exposing the patient to an additional donor.     

Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia

The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease. Genes Chromosomes Cancer 21:2–7, 1998. © 1998 Wiley-Liss, Inc.     

Positive inotropic response to alpha-adrenergic stimulation in an electrically driven rat left atrium: the role of extracellular calcium

We studied the positive inotropic response induced by alpha-adrenergic receptor stimulation in an electrically driven rat left atrium. alpha-Adrenergic stimulation resulted in a prolonged positive inotropic response that reached its maximum within 5-7 min. The kinetics of the onset of the positive inotropic response were different for pure alpha-adrenergic, pure beta-adrenergic, and mixed adrenergic stimulation. The positive inotropic responses to alpha- and beta-adrenergic agonists were not additive. The relative inotropic response to alpha-adrenergic stimulation decreased when external calcium concentration was increased and disappeared when external calcium concentration was raised to 7.0 mM. The divalent cation ionophore A23187 (1 microM) produced a threefold increase of the contractility of the atrial preparation at 1.0 mM extracellular calcium, and no further alpha-adrenergic response was observed in its presence. Calcium channel antagonists verapamil and nifedipine markedly inhibited the response to alpha-adrenergic stimulation, with little effect on the beta-adrenergic stimulation, at a calcium concentration of 0.5 mM. The inhibitory effect of calcium channel antagonists could be fully reversed by increasing the extracellular calcium concentration. Our data suggest that the alpha-adrenergic contractile response in the rat atrium involves the mobilization of extracellular calcium through verapamil-sensitive calcium channels in a mechanism different from that for the beta-adrenergic response.