Large acoustic transients induced by nonthermal melting of InSb.

We have observed large-amplitude strain waves following a rapid change in density of InSb due to nonthermal melting. The strain has been measured in real time via time-resolved x-ray diffraction, with a temporal resolution better than 2 ps. The change from the solid to liquid density of the surface layer launches a high-amplitude strain wave into the crystalline material below. This induces an effective plane rotation in the asymmetrically cut crystal leading to deflection of the diffracted beam. The uniform strain in the layer below the molten layer is 2.0(+/-0.2)%. A strain of this magnitude develops within 5 ps of the incident pulse showing that the liquid has reached the equilibrium density within this time frame. Both the strain amplitude and the depth of the strained material in the solid can be explained by assuming a reduction in the speed of sound in the nonequilibrium liquid compared to measured equilibrium values.

Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb.

The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.

Clocking femtosecond X rays.

Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling. This measurement indirectly determined the arrival time of each x-ray pulse relative to an external pump laser pulse with a time resolution of better than 60 fs rms.

Atomic-scale visualization of inertial dynamics.

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.

Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system.

BACKGROUND: Neonatal sepsis is a low incidence, high-risk disease with many sepsis work-ups performed to detect a single case. Seventy-two hours of antibiotic therapy have been traditionally recommended pending negative culture results. Improved culture media and new technology integrated into blood culture systems could shorten incubation time required to detect positive culture results. This would then change the length of antibiotic therapy in the management of the newborn infant with suspected sepsis. In addition, previous data supporting the 72-hour recommendation were retrospectively acquired, utilized nonautomated systems, and reported in an era with a different population of microorganisms cultured in special care nurseries. OBJECTIVE: Evaluate the time of incubation to detect positive blood cultures from newborn infants with suspected sepsis using a computer-assisted, automated blood culture system, ESP (Trek Diagnostic Systems, Inc, Westlake, OH). DESIGN: Prospective, observational study. PATIENTS AND SETTING: All positive blood culture results that were obtained from term and preterm newborn infants born from November 1993 through June 1997 at a publicly funded hospital with over 6000 live births per year. METHODS: As positive blood culture results were identified, data were prospectively obtained from the patient's medical record. The computer algorithm in the automated blood culture system determined the time to positivity. Time to positivity was determined for blood cultures obtained before the initiation antimicrobial therapy and compared with those cultures obtained after beginning therapy. Time to positivity was also evaluated for clinically important Gram-positive and Gram-negative bacteria and yeast. RESULTS: Four hundred fifty-five positive blood culture results were obtained from 222 patients. Gram-positive organisms accounted for 80% (366/455) of the positive culture results, Gram-negative organisms accounted for 11% (48/455), and yeast for 9% (41/455). Virtually all cultures growing clinically significant Gram-positive and Gram-negative organisms were positive by 24 to 36 hours of incubation. Cultures growing Staphylococcus epidermidis were virtually all positive after 36 to 48 hours of incubation. Of cultures growing yeast, 88% (36/41) were positive by 48 hours of incubation. There was no difference in time to positivity in pretherapy or posttherapy obtained positive blood cultures. Prenatally administered antibiotics did not affect time to positivity in positive cultures drawn on the first day of life. In a selected group of microorganisms that are the frequent cause of bacteremia in term infants, 97% and 99% of cultures were positive by 24 to 36 hours of incubation when only pretherapy cultures are evaluated. CONCLUSIONS: The ESP blood culture system identified 77%, 89% and 94% of all microorganisms at 24, 36, and 48 hours of incubation in aerobic cultures obtained from both term and preterm infants. Introduction of antimicrobial therapy did not affect time to positivity. Reducing duration of antibiotic therapy to 24 to 36 hours should be considered in term, asymptomatic newborn infants undergoing evaluation for suspected sepsis for maternal indications. Confirmation of similar rapidity of detection using other blood culture systems should be undertaken.

Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells.

Rat fetal lung cells (RFL-6) were transiently transfected with a full-length rat heme oxygenase (HO)-1 cDNA construct and then exposed to hyperoxia (95% O2-5% CO2) for 48 h. Total HO activity and HO-1 protein were measured as well as cell viability, lactate dehydrogenase (LDH) release, protein oxidation, lipid peroxidation, and total glutathione to measure oxidative injury. HO-1 overexpression resulted in increased total HO activity (2-fold), increased HO-1 protein (1.5-fold), and increased cell proliferation. Immunohistochemistry revealed perinuclear HO-1 localization, followed by migration to the nucleus by day 3. Decreased cell death, protein oxidation, and lipid peroxidation but increased LDH release and glutathione depletion were seen with HO-1 overexpression. Reactive iron content could not explain the apparent loss of cell membrane integrity. With the addition of tin mesoporphyrin, total HO activity was decreased and all changes in injury parameters were normalized to control values. We conclude that moderate overexpression of HO-1 is protective against oxidative injury, but we speculate that there is a beneficial threshold of HO-1 expression.

Endotracheal continuous positive airway pressure after rescue surfactant therapy.

OBJECTIVE: To determine if premature infants greater than 31 weeks of gestation with established hyaline membrane disease (HMD) can be treated with endotracheal continuous positive airway pressure (ETCPAP) after rescue surfactant replacement therapy. STUDY DESIGN: Retrospective study of 46 premature infants (>31 weeks of gestation) admitted to Texas Children's Hospital with HMD. Tolerance to ETCPAP after surfactant replacement was evaluated. Prenatal and postnatal characteristics and outcome were compared in the success and failure groups. Multiple logistic regression was used to determine predictive factors associated with failure. RESULTS: Thirty infants (65.2%) were successfully treated with rescue surfactant and ETCPAP. Cesarean section, higher 1-minute Apgar score, and higher FiO2 level at entry were independent predictors of failure to remain on CPAP due to hypoxemia (56.3%), hypercapnia (31.2%), and apnea (12.5%). In the success group duration of intubation (p < 0.001), oxygen administration (p < 0.01), >40% oxygen requirement (p < 0.001), hospital stay (p < 0.05), and respiratory support on day 7 (p < 0.001) were significantly favorable. CONCLUSION: Two thirds of infants greater than 31 weeks of gestation, with HMD needing rescue surfactant treatment, can be successfully managed with ETCPAP.

Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal.

Glutathione reductase (GR) is an important component of cellular antioxidant defense functions. Although GR activities are found in mitochondria and cytoplasm, the sorting mechanisms of mammalian GR into mitochondria have not been elucidated. To identify the mouse GR gene structure, including a sequence for a potential mitochondrial targeting signal (MTS), we screened a mouse genomic library and isolated four contiguous clones that covered the entire coding region of the gene. The coding region is composed of 13 exons. Exon 1 has two in-frame start codons separated by a sequence for an arginine-rich peptide segment. Expression studies, in which Chinese hamster ovary cells were transiently transfected with a plasmid containing the first 78 bp of the mouse exon 1 attached 5' to the human GR cDNA, showed marked and selective increases in mitochondrial GR activities. The data indicate that this 78 bp sequence encodes a potential MTS for GR in mice.

Increased platelet aggregation due to chilling to 20 degrees C is not related to increased sensitivity to agonists.

BACKGROUND: Previous studies suggested that chilled platelets have a greater sensitivity to agonists than do platelets aggregated at 37 degrees C. STUDY DESIGN AND METHODS: Washed platelets were aggregated at 20 or 37 degrees C with ADP (0-20 microM), arachidonic acid (0-200 microM), or the thromboxane mimetic U46619 (0-9 nM). RESULTS: Chilling caused a significant (p < or = 0.05) increase in spontaneous platelet aggregation (> 27% at 20 degrees C vs < 5% at 37 degrees C) and spontaneous dense granule release (> 0.01 nM of ATP at 20 degrees C vs. 0 nM of ATP at 37 degrees C), ADP and U46619 caused a significantly greater aggregation response and dense granule release at 20 degrees C, although there was no change in agonist sensitivity of platelets (effective dose of agonist necessary to induce 50% aggregation [ED50]: 1.00 +/- 0.35 microM ADP at 20 degrees C and 1.63 +/- 0.47 microM ADP at 37 degrees C; 8.26 +/- 3.65 pM U46619 at 20 degrees C and 18.97 +/- 4.82 pM U46619 at 37 degrees C). Platelets aggregated with arachidonic acid showed a significant decrease in aggregation and agonist sensitivity at 20 degrees C (ED50 118.7 +/- 44.4 microM) from those at 37 degrees C (ED50 25.6 +/- 7.2 microM), possibly as a result of the reduced enzymatic activity of cyclooxygenase and thromboxane synthase at the lower temperature. CONCLUSION: The data suggested that washed platelets chilled to 20 degrees C and aggregated are not more sensitive to agonists than are 37 degrees C controls, but rather that chilled platelets undergo greater spontaneous aggregation.

Mitochondrial targeting of glutathione reductase requires a leader sequence.

Glutathione reductase (GR), which catalyzes the conversion of glutathione disulfide to glutathione, is encoded in nuclear DNA, but is active in cytoplasm and mitochondria. However, analyses of known protein and DNA sequences for human GR have not revealed a potential mitochondrial targeting signal (MTS). We generated two 5'-truncated GR clones, which resulted in omission of the N-terminal 5 or 10 amino acids, to disable a potential targeting signal, and generated two GR clones containing synthetic MTS cDNAs. Transfection of Chinese hamster ovary cells with the full length human GR cDNA or with the 5'-truncated clones increased cytosolic GR activities 6- to 14-fold, but increased mitochondrial activities less than 2-fold. In contrast, transfection with either of the GR clones containing MTS cDNAs increased GR activities in mitochondria more than 24-fold. We conclude that the existing protein and DNA sequences for human GR do not contain a MTS and that such a signal is needed for effective mitochondrial targeting.

Antenatal steroids are associated with less need for blood pressure support in extremely premature infants.

OBJECTIVE: To determine if antenatal steroids decrease the amount of blood pressure support required by extremely premature infants between 23 and 27 weeks' gestation. DESIGN: Retrospective cohort study. SETTING: Texas Children's Hospital neonatal intensive care unit from January 1986 to December 1991. PARTICIPANTS: Two hundred forty premature infants between 23 and 27 weeks' gestation who survived at least 48 hours. MAIN OUTCOME MEASURES: The amount of blood pressure support received in the form of dopamine and colloid. Secondary analysis investigated differences in mortality, respiratory support requirements, the incidence of intraventricular hemorrhage, necrotizing enterocolitis, infection, retinopathy of prematurity requiring surgery, and the length of hospitalization. RESULTS: During the first 48 hours of life, premature newborns exposed to antenatal corticosteroids were less likely to receive dopamine for blood pressure support (47% vs 67%), and if they did, the amount of dopamine expressed as a dopamine score was less than that received by those infants not exposed to antenatal corticosteroids (281 +/- 240 vs 407 +/- 281). Those exposed to antenatal corticosteroids also had a lower mortality rate (8% vs 24%) and lower respiratory support requirements. The incidence of grade 3 or 4 intraventricular hemorrhage was 8% in infants exposed to antenatal corticosteroids and 17% in infants not exposed. No difference was found in the incidence of necrotizing enterocolitis, infection, or retinopathy of prematurity requiring surgery, or length of hospitalization. CONCLUSION: Receipt of antenatal corticosteroids is associated with less need for blood pressure support during the first 48 hours after birth in premature infants between 23 and 27 weeks' gestation.

Current issues in Texas neonatology.

Since almost 10% of the births in the United States occur in Texas, issues that affect neonatal care in Texas are important for both the state and the nation. Although overall statistics are similar for the state and nation, closer examination reveals a need for improvement in specific areas, namely prenatal care, black and Hispanic mortality, and low birth-weight rates. Lay midwifery regulation has been an important concern in Texas. Surfactant use and education to prevent birth asphyxia have had a positive impact on perinatal health, contributing to public health efforts to improve perinatal outcome.

Endotoxin induces glutathione reductase activity in lungs of mice.

Glutathione reductase catalyzes the NADPH-dependent conversion of glutathione disulfide to glutathione and helps protect the lung from injury by reactive oxygen. In animals allowed to breathe nearly 100% oxygen, the activities of other antioxidants in the lung can be induced by treatment with endotoxin, and this induction is associated with increased tolerance to hyperoxia. The purpose of this study was to see whether glutathione reductase activity in the lungs of mice increased with endotoxin treatment alone. We studied 60 FVB mice (20 males and 40 females). Half received endotoxin (500 micrograms/kg) intraperitoneally at time 0 and 24 h, and the controls received an equal volume of saline. At 48 h we killed the mice and removed their lungs. Treatment of mice with endotoxin increased glutathione reductase activity in the lung 55% (0.035 +/- 0.005 to 0.054 +/- 0.010 mumol NADPH reduced/min/mg protein; mean +/- SD; endotoxin different from control, p < 0.001). The increase in activity was the same for male and female mice. We measured the specific protein for glutathione reductase by Western analysis and mRNA for glutathione reductase using a slot-blot analysis and found that both increased roughly 2-fold with endotoxin treatment. This suggests that endotoxin treatment resulted in either increased rate of transcription of glutathione reductase mRNA or increased mRNA stability. We conclude that endotoxin treatment increases glutathione reductase activity in the lung and that this increase in activity may play a role in subsequent protection from hyperoxia.

Effects of hypothermia upon endothelial cells: mechanisms and clinical importance.

The endothelial cell is vital in the regulation of blood vessel wall structure, vasomotor tone, and thrombogenicity. Hypothermic temperatures alter both the physiological and biochemical dynamics of endothelial cells. However, there has been no systematic investigation of the influence of cold temperatures upon endothelial cell biology. This review summarizes the current clinical areas of interests, identifies the problems, and addresses the fundamental requirement for further research in endothelial cell cryobiology.