Risk of uterine rupture in Australian women attempting vaginal birth after one prior caesarean section: a retrospective population-based cohort study.

OBJECTIVE: Higher risks of uterine rupture have been reported among women attempting vaginal birth after caesarean (VBAC) particularly following induction with prostaglandins, compared with women who do not labour. This study aimed to estimate these risks as well as that associated with oxytocin use. DESIGN: Population-based retrospective cohort study involving all women who had their first births by caesarean. In their second birth, risks of uterine rupture among women without labour and women who had labour augmented or induced were compared with women who gave birth after spontaneous labour. SETTING: Four Australian states in 1998-2000. POPULATION: Women on pregnancy outcome databases with a second birth after a prior caesarean for their first birth. METHODS: From 29, 008 women identified from the databases, those with uterine rupture were identified and validated using hospital case records. MAIN OUTCOME MEASURE: Uterine rupture. RESULTS: The risk of complete uterine rupture among women without labour was 0.01%. The risk in spontaneous labour without augmentation was 0.15%, considerably higher when there was augmentation with oxytocin (1.91%). The risk with induction of labour was 0.54% for oxytocin alone, 0.68% for prostaglandin alone, 0.63% without either and 0.88% when they were combined. Compared with spontaneous labour, risks were increased three- to five-fold for any induction, six-fold for prostaglandin combined with oxytocin and 14-fold for augmentation with oxytocin. CONCLUSIONS: Careful consideration should be given to the use of oxytocin for augmentation of labour or induction by any method for women with a previous caesarean in view of increased risks of uterine rupture.

Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn.

This study examined the impact of the tyrosine kinase Lyn on erythropoietin-induced intracellular signaling in erythroid cells. In J2E erythroleukemic cells, Lyn coimmunoprecipitated with numerous proteins, including SHP-1, SHP-2, ras-GTPase-activating protein, signal transducers and activators of transcription (STAT) 5a, STAT5b, and mitogen-activated protein kinase; however, introduction of a dominant-negative Lyn (Y397F Lyn) inhibited the interaction of Lyn with all of these molecules except SHP-1. Cells containing the dominant-negative Lyn displayed altered intracellular phosphorylation patterns, including mitogen-actiated protein kinase, but not erythropoietin receptor, Janus-activated kinase (JAK) 2, or STAT5. As a consequence, erythropoietin-initiated differentiation and basal proliferation were severely impaired. Y397F Lyn reduced the protein levels of erythroid transcription factors erythroid Kruppel-like factor and GATA-1 up to 90%, which accounts for the inability of J2E cells expressing Y397F Lyn to synthesize hemoglobin. Although Lyn was shown to bind several sites on the cytoplasmic domain of the erythropoietin receptor, it was not activated when a receptor mutated at the JAK2 binding site was ectopically expressed in J2E cells indicating that JAK2 is the primary kinase in erythropoietin signaling and that Lyn is a secondary kinase. In normal erythroid progenitors, erythropoietin enhanced phosphorylation of Lyn; moreover, exogenous Lyn increased colony forming unit-erythroid, but not burst forming uniterythroid, colonies from normal progenitors, demonstrating a stage-specific effect of the kinase. Significantly, altering Lyn activity in J2E cells had a profound effect on the development of erythroleukemias in vivo: the mortality rate was markedly reduced and latent period extended when either wild-type Lyn or Y397F Lyn was introduced into these cells. Taken together, these data show that Lyn plays an important role in intracellular signaling in nontransformed and leukemic erythroid cells.

Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo.

J2E cells produce rapid, fatal erythroleukemias in vivo but still respond to erythropoietin (epo) in vitro by differentiating, proliferating and remaining viable in the absence of serum. Mutant epo receptors were introduced into these cells to determine whether they could influence the different biological responses to epo in vitro and the development of erythroleukemias. Three mutant receptors were used as cytoplasmic truncation mutants Delta257 and Delta321 (above box 1 and below box 2 respectively), and the cytoplasmic point mutant W282R (defective for JAK2 activation). Strikingly, the Delta321 mutation produced a hyper-sensitive response in vitro to epo-induced differentiation and viability, but not to proliferation. In contrast with the Delta321 receptor, the Delta257 and W282R mutants inhibited all biological responses to epo due to impaired JAK2 phosphorylation. Significantly, erythroleukemias took almost twice as long to develop with cells containing the W282R mutation, indicating that JAK2 plays an important role in the emergence of these leukemias. These data demonstrate that mutant epo receptors dominantly altered responses of J2E cells to epo in culture and the development of erythroleukemias. Oncogene (2000) 19, 953 - 960.

Restriction fragment length polymorphisms of the human aldose reductase gene: a preliminary report.

Abnormal metabolism through the polyol pathway during episodes of hyperglycaemia is implicated in the development of the chronic complications of diabetes. Since aldose reductase is the first and ratelimiting enzyme of the polyol pathway, it is predicted that restriction fragment length polymorphisms at the aldose reductase gene locus may influence catalytic activity and determine individual susceptibility to the diabetic complications. This paper reports the existence of EcoRI and TaqI restriction fragment length polymorphisms at the human aldose reductase locus.

Sociocultural influences and self-care practices of middle adolescents.

The purpose of this study was to describe general self-care practices of middle adolescents. In addition, the relation between general self-care practices and specific sociocultural characteristics including socioeconomics and church attendance were explored. Orem's self-care theory and developmental theory provided the framework for the investigation. Findings from the sample of 15- and 16-year-old adolescents (n = 425) showed that they are engaging in self-care practices. The influence of sociocultural characteristics on self-care practices was supported. Implications from the study include the need to continue research endeavors that describe, explain, and predict health behavior in child and adolescent populations. Practicing nurses in diverse health care settings should consider the results of this study when working with adolescents and their families from diverse sociocultural backgrounds. Results from this investigation should be incorporated into the planning of health education programs for the adolescent population.

Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice.

Viral DNA vaccines encoding the glycoprotein B (gB) of cytomegalovirus provide partial protective immunity upon challenge with infectious virus. Although it is known that type I IFN can stimulate the adaptive immune response, their direct use in vaccines has been limited. Here we show that coimmunisation of type I IFN and gB CMV DNA constructs enhances protective immunity in mice. In vivo expression of IFN transgenes ranged from 1.2 to 2.0 x 10(4) IU/g tibialis anterior muscle. Viral titre in major target organs and the severity of acute CMV-induced myocarditis was reduced preferentially with either IFN-alpha 9 or IFN-beta, but not with IFN-alpha 6, coimmunisation. However, all IFN subtypes investigated markedly reduced chronic myocarditis in gB-vaccinated mice. The early antiviral IgG1 and IgG2a titres were enhanced with IFN-beta coimmunisation. TNF and IL-10 was increased in response to MCMV infection in mice coimmunised with IFN subtypes and viral gB DNA. Indeed T cells from IFN-inoculated mice reduced myocarditis upon in vivo transfer. These results suggest that select type I IFNs may act as a natural adjuvant for the immune response against CMV infection. Type I IFN DNA coimmunisation may provide increased efficacy for viral vaccines and subsequently modulate post-viral chronic inflammatory disorders.

Parenting and childrearing attitudes among high school students.

A descriptive study to assess parenting and childrearing attitudes was conducted among 502 high school students in a greater metropolitan area in the Southeast. The Adult-Adolescent Parenting Inventory (Bavolek, 1984) was used to identify students' scores on four constructs associated with abusive parenting: inappropriate parental expectations, lack of empathy toward the child, value of physical punishment, and parent-child role reversal. Several group differences were found by sex, race, grade, and birth order. Ten percent of students scored consistently low and could be targeted for education programs to increase parenting knowledge and skill.

Amiloride suppresses erythropoietin-induced proliferation and MAP kinase, but potentiates differentiation of J2E cells.

The J2E erythroid cell line proliferates and differentiates in response to erythropoietin (epo). Here we demonstrate that the diuretic amiloride can suppress normal and hormone-induced cell division in a dose-dependent manner. In the presence of amiloride, cell numbers did not increase, [3H]thymidine incorporation decreased, and fewer cells were observed in the S, G2, and M phases of the cell cycle. In addition, the levels of proliferating cell nuclear antigen, a subunit of DNA polymerase delta, fell. In marked contrast, epo-initiated differentiation was potentiated when J2E cells were cultured with the drug: the number of benzidine-positive cells increased, hemoglobin content per cell rose, and more morphologically mature cells were produced. Immunoblotting with anti-phosphotyrosine antibodies revealed that amiloride reduced the number of phosphorylated proteins in epo-stimulated cells. Moreover, the protein content of p42 and p44 MAP kinases was noticeably downregulated in amiloride-treated cultures. These data indicate that amiloride may interfere with epo-induced signaling cascades within J2E cells which result in restricted cell division and promotion of maturation.