Time to positivity of blood cultures for children with Streptococcus pneumoniae bacteremia.

We report on a 3-year (1 January 1996 through 31 December 1999) retrospective chart review of children with Streptococcus pneumoniae bacteremia to identify the time to identification of growth of S. pneumoniae in blood culture and to attempt to identify clinical predictors of early versus late growth of S. pneumoniae in culture. The time to detection of S. pneumoniae in blood culture for immunocompetent patients ranged from 4.4 to 25.9 hours (h), with a mean of 11.5 h (standard deviation, 2.8). There was no difference in the time to detection for immunocompromised versus immunocompetent patients. The 10th and 90th deciles for time to detection among immunocompetent patients were 9.2 and 14.0 h, respectively. There were no differences in white blood cell count, absolute neutrophil count, or height of fever between the lowest and highest decile groups. Ninety percent of blood cultures yielding S. pneumoniae are noted positive within 14 h, and no clinical or laboratory parameters accurately predicted early versus late growth of S. pneumoniae in blood culture.

Neonatal hypoperistalsis associated with perinatal zidovudine administration.

OBJECTIVE: This paper presents the cases of two infants exposed to perinatal zidovudine in whom hypoperistalsis and intestinal pseudoobstruction developed. STUDY DESIGN: Clinical case reports were prepared of two infants born to women infected with human immunodeficiency virus who were treated with perinatal zidovudine at a single inner-city medical school. RESULTS: None of the previously described causes for this rare condition contributed to the symptoms in these two infants. In addition, the symptoms resolved shortly after discontinuation of zidovudine administration. CONCLUSIONS: Although a strict cause-and-effect relationship between the medication and the impairment in intestinal peristalsis was not proved, awareness of this association should be helpful for physicians caring for infants exposed to perinatal zidovudine.

Phosphotyrosine protein phosphatases activation by ACTH in rat adrenal gland.

The steady state level of most cellular phosphoproteins is dependent on the relative catalytic activities of intracellular protein kinases and phosphatases. In adrenal cortex, ACTH acts through PKA activation and Ser/Tre phosphorylation. Phosphatases involved in this pathway are not completely described, particularly the role of phosphotyrosine protein phosphatase (PTP) activity on ACTH action. We investigated potential changes in PTPs activity in adrenal gland upon in vivo and in vitro PKA activation. In vivo ACTH stimulates cytosolic PTP activity (2-fold). Similar effect is detected by in vitro stimulation. In accordance with the effects of ACTH on PTP activity, cell permeable PTP inhibitors block ACTH stimulation on adrenal zona fasciculata (ZF) cells: ACTH (1 nM) = 108.2 +/- 3.5 ng corticosterone/10(5) cells vs. ACTH + phenylarsine oxide (2 nM) = 60 +/- 4 (P < 0.001) and ACTH + pervanadate (10 mM) = 68 +/- 2 (P < 0.01). These results are reproduced when cells are stimulated with cAMP. The inhibition is not observed when steroidogenesis is supported by 22(R)OH cholesterol. We describe, for the first time, a hormonal regulation of PTP activity. According to the effect of PTP inhibitors on steroid production activated by ACTH we propose that PTP activation is a crucial event in hormone action in the steroidogenic pathway. We also propose that PTP activity is located after PKA activation and prior to cholesterol transport to the inner mitochondrial membrane.

Site of action of proteinases in the activation of steroidogenesis in rat adrenal gland.

We have investigated the effect of the proteinase inhibitors 1,10-phenantroline (OP) and phenylmethylsulfonyl fluoride (PMSF) on steroidogenesis in rat adrenal cortex. Both PMSF and OP inhibited adrenocorticotropin (ACTH)- and 8-Br cAMP-induced stimulation of corticosterone synthesis. On the contrary, arachidonic acid-induced stimulation of corticosterone synthesis was only slightly inhibited by PMSF and unchanged by OP. Intra- and extracellular cAMP levels were determined by radioimmunoassay. While PMSF did not affect neither the intra- nor the extracellular cAMP levels, OP decreased the intra- and extracellular levels of unstimulated as well as ACTH-stimulated cells. The site of action of the proteinase inhibitors was also studied by recombination of mitochondria with the different subcellular fractions in vitro. Addition of PMSF abolished the stimulation achieved by in vitro activation of cytosol by cAMP and PKA. On the other hand, OP completely inhibited the activation of mitochondria. Our results provide evidence for the involvement of proteinases in ACTH-induced stimulation of steroidogenesis in adrenal cortex both prior to the release of arachidonic acid and at the level of cholesterol transport from the outer to the inner mitochondrial membrane.

ACTH-dependent proteolytic activity of a novel phosphoprotein (p43) intermediary in the activation of phospholipase A2 and steroidogenesis.

Arachidonic acid (AA) and the lipooxygenase products have been shown to play an obligatory role in the mechanism of action of LH and ACTH, at a point after cAMP-dependent phosphorylation. We have demonstrated the presence of a phosphoprotein (p43) that responds to cAMP signals to induce steroid synthesis in adrenocortical tissue, an effect that is blocked by phospholipase A2 inhibitors. In this report we demonstrate that p43 exhibits autoproteolytic activity that is regulated by ACTH. Protein purified from ACTH-treated animals exhibited degradation in some of the isoforms resolved on two dimensional gel electrophoresis. Proteinase inhibitors (PMSF and 1,10 phenantroline) inhibited steroid synthesis induced by ACTH and 8-Br-cAMP in intact cells. Addition of exogenous AA reverted in part that inhibition. Here we present evidence for a hormone-regulated proteolytic activity of p43 and for the inhibition of steroidogenesis by proteinase inhibitors acting prior to the release of arachidonic acid.