Pump in Parallel-Mechanical Assistance of Partial Cavopulmonary Circulation Using a Conventional Ventricular Assist Device.

Mechanical assistance of systemic single ventricle is effective in pulling blood through a cavopulmonary circuit. In patients with superior cavopulmonary connection, this strategy can lead to arterial desaturation secondary to increased inferior caval flow. We hypothesized that overall augmentation in cardiac output with mechanical assistance compensates for the drop in oxygen saturation thereby maintaining tissue oxygen delivery (DO2).

Influence of central hemodynamics on VV ECMO oxygen delivery in neonatal animal model.

Background: Recirculation of oxygenated blood in venovenous extracorporeal membrane oxygenation (VV ECMO) can decrease the oxygen delivery provided by the ECMO support. This study investigated the influence of central hemodynamics and catheter position on the amount of recirculation and oxygen delivery during VV ECMO.

Methods: Recirculation was measured in seven newborn lambs (mean weight 4.

Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity.

Interferon-α (IFNα) has been prescribed to effectively treat multiple myeloma (MM) and other malignancies for decades. Its use has waned in recent years, however, due to significant toxicity and a narrow therapeutic index (TI). We sought to improve IFNα's TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to MM cells, and, second, by introducing an attenuating mutation into the IFNα portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells.

Effect of mechanical assistance of the systemic ventricle in single ventricle circulation with cavopulmonary connection.

Background: Previous attempts to support single ventricle circulation mechanically have suggested that a custom-built assist device is needed to push, rather than pull, through the pulmonary circulation. We hypothesized that using a conventional ventricular assist device, with or without conversion of a total cavopulmonary connection to a bidirectional Glenn cavopulmonary connection, would allow assistance by pulling blood through the circuit and improve the cardiac index (CI).

Methods: Cavopulmonary connections were established in each of 5 Yorkshire pigs (25 kg) using ePTFE conduits in a Y configuration with appropriate clamping of the limbs of the Y to achieve a total cavopulmonary Fontan connection (TCPC), superior vena cava cavopulmonary connection (SVC Glenn), and inferior vena cava cavopulmonary connection (IVC Glenn).

Evaluation of the new generation dual-lumen catheter for neonatal ECMO.

Objectives: The purpose of this study was to compare the newly designed dual-lumen venovenous catheter (VR13, OriGen Biomedical, Austin, TX) with the current dual-lumen catheter (VV12, OriGen Biomedical).

Methods: Five newborn lambs, 1 to 5 days old and weighing 4.2 ± 0.

Comparison of the effect of venovenous versus venoarterial extracorporeal membrane oxygenation on renal blood flow in newborn lambs.

Unlabelled: Venovenous extracorporeal membrane oxygenation (VV ECMO) using double lumen catheters is an alternative to venoarterial (VA) ECMO and allows for total blood flow using the patient's cardiac output in comparison to partial blood flow provided during VA ECMO.

Objective: To compare the effects of VV versus VA ECMO on renal blood flow.

Design: Prospective study.

Improved oxygenation with reduced recirculation during venovenous ECMO: comparison of two catheters.

Objectives: To determine whether the new double-lumen catheter made by OriGen Biomedical (Austin, TX) for venovenous (VV) extracorporeal membrane oxygenation (ECMO) would reduce recirculation and improve oxygenation during VV ECMO when compared with the Kendall double-lumen catheter (Kendall Healthcare Products, Mansfield, MA).

Design: Prospective intervention study.

Setting: The animal research laboratory at Children's National Medical Center, Washington, DC.

Continuous blood gas monitoring using an in-dwelling optode method: comparison to intermittent arterial blood gas sampling in ECMO patients.

Introduction: The ability to measure postmembrane arterial blood gases is essential in the management of critically ill neonates treated with extracorporeal membrane oxygenation (ECMO). A new technology using, the Paratrend 7 system (Diametrics Medical, High Wycombe,UK) allows for continuous measurement of pH, PCO(2) and PO(2), and calculates oxygen saturation, bicarbonate, and base excess.

Objective: To evaluate and compare the results of continuous blood gas measurement using the Paratrend 7 system with a standard system of blood gas analysis in our intensive care unit.

A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription.

We have identified a novel promoter element that confers M/G1-specific transcription in Saccharomyces cerevisiae. This element, which we call an ECB (early cell cycle box), was first identified in the SWI4 promoter, but it is also present in the promoter of a G1 cyclin CLN3, as well as in the promoters of three DNA replication genes: CDC6, CDC47, and CDC46. Transcripts from all five of these genes oscillate during the cell cycle and peak at the M/G1 boundary, as do isolated ECB elements in reporter constructs.

Cell cycle-dependent transcription of CLN1 involves swi4 binding to MCB-like elements.

Two promoter elements have been defined that activate G1/S-specific transcription in Saccharomyces cerevisiae. SCB elements (CACGAAA) are activated by the Swi4-Swi6 complex, and MCB elements (ACGCGTNA) are activated by the Mbp1-Swi6 complex. CLN1 encodes a cyclin which is expressed during this interval, and requires Swi4 and Swi6 for peak transcription, but it has no consensus SCB elements in its promoter.

Cell cycle-regulated phosphorylation of Swi6 controls its nuclear localization.

The Swi6 transcription factor, required for G1/S-specific gene expression in Saccharomyces cerevisiae, is highly phosphorylated in vivo. Within the limits of resolution of the peptide analysis, the synchrony, and the time intervals tested, serine 160 appears to be the only site of phosphorylation in Swi6 that varies during the cell cycle. Serine 160 resides within a Cdc28 consensus phosphorylation site and its phosphorylation occurs at about the time of maximal transcription of Swi6- and Cdc28-dependent genes containing SCB or MCB elements.

Improved oxygenation with reduced recirculation during venovenous extracorporeal membrane oxygenation: evaluation of a test catheter.

Objective: To determine whether modifications of the original design of a double-lumen, venovenous, extracorporeal membrane oxygenation (ECMO) catheter would reduce recirculation and improve oxygenation during venovenous ECMO.

Design: Prospective, interventional study.

Setting: The animal research laboratory at The Children's National Medical Center.

Three independent forms of regulation affect expression of HO, CLN1 and CLN2 during the cell cycle of Saccharomyces cerevisiae.

The G1 cyclins (CLNs) bind to and activate the CDC28 kinase during the G1 to S transition in Saccharomyces cerevisiae. Two G1 cyclins are regulated at the RNA level so that their RNAs peak at the G1/S boundary. In this report we show that the cell cycle regulation of CLN1 and CLN2 is partially determined by the restricted expression of SW14, a known trans-activator of SCB elements.

Differential effects of Cdc68 on cell cycle-regulated promoters in Saccharomyces cerevisiae.

Swi4 and Swi6 form a complex which is required for Start-dependent activation of HO and for high-level expression of G1 cyclin genes CLN1 and CLN2. To identify other regulators of this pathway, we screened for dominant, recessive, conditional, and allele-specific suppressors of swi4 mutants. We isolated 16 recessive suppressors that define three genes, SSF1, SSF5, and SSF9 (suppressor of swi four).

Multiple SWI6-dependent cis-acting elements control SWI4 transcription through the cell cycle.

The Saccharomyces cerevisiae SWI4 gene encodes an essential transcription factor which controls gene expression at the G1/S transition of the cell cycle. SWI4 transcription itself is cell cycle regulated, and this periodicity is crucial for the normal cell cycle regulation of HO and at least two of the G1 cyclins. Since the regulation of SWI4 is required for normal cell cycle progression, we have characterized cis- and trans-acting regulators of SWI4 transcription.

In vitro evaluation of the Mera Silox-S 0.5 and 0.8 m 2 silicone hollow-fibre membrane oxygenator for use in neonatal ECMO.

The Mera Silox-S is a silicone hollow-fibre membrane oxygenator made up of thousands of fibres in a clear polycarbonate housing. Being a silicone membrane it does not have the plasma leakage problem associated with conventional microporous hollow fibres when used in a long-term application. This device (Mera Senko Medical Instrument Co.

Cell cycle-specific expression of the SWI4 transcription factor is required for the cell cycle regulation of HO transcription.

Expression of the HO endonuclease triggers mating-type switching in Saccharomyces cerevisiae. Transcription of the HO gene is start-dependent and restricted to the late G1/early S phase of haploid mother cells. The HO promoter contains 10 copies of a cell cycle-regulated upstream activation sequence, which is activated by SWI4 and SWI6.

Maximum blood flow rates for arterial cannulae used in neonatal ECMO.

The arterial cannulae used in neonatal ECMO cause hemolysis and red blood cell damage at elevated blood flows. Hemolysis in extracorporeal circuits has been found to occur with shear stress greater than 132 dynes/cm2, turbulence as measured by Reynold's number greater than 1,000, and velocity greater than 120 to 200 cm/sec. These parameters need to be considered when sizing the proper arterial cannula for a required flow rate.

Low incidence of acquired cytomegalovirus infection in neonates transfused with washed red blood cells.

To define the incidence of cytomegalovirus (CMV) infection in infants given transfusions of washed blood cells from random donors, 100 infants who were identified as being CMV seronegative at birth were resampled at hospital discharge and again six weeks after hospitalization. All infants received washed red blood cell products; 37 infants received nonleukodepleted platelets and/or plasma. There were 7.

Techniques for warming red blood cells packaged in different containers for neonatal use.

Essential to the management of the sick, low birth weight infant is maintenance of a neutral thermal environment by use of convection incubators and radiant warmers. Manipulation of the infant in preparation for transfusion and the transfusion of cold blood could theoretically lower the infant's body temperature, subsequently contribute to cold stress, and concomitantly increase metabolic demands and oxygen requirements. The authors evaluated different pretransfusion manipulations of syringe aliquots and bags of blood in an effort to provide a clinically acceptable product for transfusion to sick, very low birth weight infants.

Implications of the corneal temperature range in the prediction of laser thermal damage.

Corneal temperatures of the rhesus monkeys have been measured under conditions that may exist during laser experiments. The minimum and maximum temperatures found for all experimental conditions were 29.54 degrees C and 39.