Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: longitudinal study.

OBJECTIVES: Observational studies have shown that low cerebroplacental ratio (CPR) values predict an increased risk of adverse perinatal outcome. The inverse ratio, i.e. the umbilicocerebral ratio (UCR), has been suggested to be a better predictor as it rises with increasing degree of fetal compromise. However, longitudinal reference ranges for UCR have not been established, and whether gestational-age-dependent changes in CPR or UCR differ between male and female fetuses has not been studied. Thus, the aims of this study were to investigate sex-specific, gestational-age-associated serial changes in CPR and UCR during the second half of pregnancy and to establish longitudinal reference ranges. METHODS: This was a secondary analysis of prospectively collected data from a dual-center longitudinal observational cohort study of low-risk singleton pregnancies. Doppler blood-flow velocity waveforms were obtained serially from the umbilical artery (UA) and fetal middle cerebral artery (MCA) from 19-41 weeks' gestation, and pulsatility indices (PIs) were determined. CPR and UCR were calculated as the ratios MCA-PI/UA-PI and UA-PI/MCA-PI, respectively. The course and outcome of pregnancies were recorded, and the sex of the fetus was determined after delivery. Reference intervals for CPR and UCR were constructed using multilevel modeling, and gestational-age-specific Z-scores in male and female fetuses were compared. RESULTS: Of a total of 299 pregnancies enrolled, 284 (148 male and 136 female fetuses) were included in the final analysis, and 979 paired measurements of UA-PI and MCA-PI were used to construct sex-specific longitudinal reference intervals. The relationship of both CPR and UCR with gestational age was U-shaped, but in opposite directions. There was a small but significant difference in Z-scores of CPR and UCR between male and female fetuses throughout the second half of pregnancy (P = 0.007). CONCLUSIONS: We have established longitudinal reference ranges for CPR and UCR suitable for serial monitoring, with the possibility of refining assessment by using fetal sex-specific ranges and conditioning by a previous measurement. The clinical significance of such refinements needs further evaluation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of adverse perinatal outcome of small-for-gestational-age pregnancy using size centiles and conditional growth centiles.

OBJECTIVE: To test whether adding conditional growth centiles to size centiles of estimated fetal weight (EFW) improves prediction of adverse perinatal outcome in pregnancies with or at risk of having a small-for-gestational-age (SGA) fetus. METHODS: This prospective longitudinal study included pregnant women at risk of or diagnosed with an SGA (≤ 5(th) centile) fetus. They underwent serial ultrasound measurements and the final two were included in the analyses for this study. The EFW was categorized into normal (> 5(th) or 10(th) centile) and abnormal (≤ 5(th) or 10(th) centile) for size and conditional growth before entering the variables into log-binomial regression analyses. Adverse outcomes were delivery < 37 weeks, operative delivery due to fetal distress, 5-min Apgar score < 7, newborn hypoglycemia (glucose < 2.0 mmol/L), admission to the neonatal intensive care unit and perinatal mortality. A combined outcome variable ('any adverse outcome') included one or more adverse outcomes. RESULTS: Complete biometric data were obtained for 211 women. Conditional growth and size centiles contributed independently to the prediction of adverse outcome. Combining conditional growth and size centiles significantly improved the prediction of outcomes compared with size centiles alone (e.g. for 5(th) centile cut-off for any adverse outcome, P = 0.023, log-likelihood test). Using a 5(th) centile threshold, for any adverse outcome, the specificity of 78% (95% CI, 70-84%) using size centile as a predictor was improved to 94% (95% CI, 89-97%) when conditional growth centile was added to the model, whereas the sensitivity was not significantly changed (60% (95% CI, 49-69%) vs 39% (95% CI, 30-50%)). CONCLUSIONS: Size centiles and conditional growth centiles contribute independently to the prediction of adverse perinatal outcome, and their combination further improves the prediction model. The results support an increased use of conditional growth centiles in the monitoring of fetuses at risk. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Different oxygenators for cardiopulmonary bypass lead to varying degrees of human complement activation in vitro.

Complement activation was studied in vitro with six different membrane and bubble oxygenators for cardiopulmonary bypass. There was a similar increase in terminal (C5 to C9) activation with all oxygenators (p less than 0.001), ranging from 281% (117% to 444%) to 453% (225% to 680%) after 60 minutes (median and 95% confidence intervals). C3 activation was not observed with a hollow fiber membrane and a soft shell bubble oxygenator. On the other hand, a capillary membrane, a sheet membrane, a nonporous membrane, and a hard shell bubble oxygenator all induced a similar increase in C3 activation (p less than 0.01), ranging from 107% (23% to 346%) to 272% (88% to 395%) after 60 minutes. The differences in C3 activation could not be explained by the blood contact materials or any other single factor known to induce activation, which suggests that overall complement activation during cardiopulmonary bypass is a multifactorial effect. The tubing set per se induced only minor C3 activation but contributed to the overall formation of terminal complement complex. The study further indicates that an arterial line blood filter prevents activated neutrophils from being reinfused to the patient and should be used regardless of type of oxygenator.

Complement activation during extracorporeal circulation. In vitro comparison of Duraflo II heparin-coated and uncoated oxygenator circuits.

The degree of complement activation during cardiopulmonary bypass is considered a valuable parameter of biocompatibility of the extracorporeal circuit. In an in vitro setting with a heart-lung machine primed with fresh whole blood and saline solution, the C3 activation products C3b, iC3b, and C3c and the terminal complement complex were measured in double-antibody enzyme immunosorbent assays. No differences were found between seven sets treated with Duraflo II heparin coating and seven uncoated sets after 2 hours of circulation. C3 activation products (expressed as median and 95% confidence intervals) increased from 4.5 AU (2.8 to 12.3 AU) to 16.5 AU (10.0 to 19.4 AU) in the uncoated sets (p = 0.02) and from 4.6 AU (2.2 to 5.8 AU) to 19.3 AU (3.5 to 27.1 AU) in the coated sets (p = 0.02). Terminal complement complex increased from 5.7 AU (2.7 to 11.3 AU) to 13.6 AU (8.2 to 17.8 AU) in the uncoated sets (p = 0.02) and from 7.9 AU (4.6 to 11.4 AU) to 17.3 AU (9.4 to 35.1 AU) in the coated sets (p = 0.02). A significant drop in thrombocyte levels was observed in both coated and uncoated sets. In a supplementary series, the sterilization process did not influence the results. Although Duraflo II heparin coating is considered highly effective in preventing coagulation, it did not prevent complement activation in the present in vitro study. We hypothesize that the mode by which the heparin molecule is bound to the surface may be essential to obtain effects on both coagulation and complement system.

Extracorporeal membrane oxygenation using a centrifugal pump and a servo regulator to prevent negative inlet pressure.

BACKGROUND: We studied whether negative inlet pressure created by a centrifugal pump during extracorporeal membrane oxygenation damages blood. METHODS: Fresh, whole human blood and primer were circulated through a test circuit, applying an inlet pressure of 0, -50, or -100 mm Hg. Thereafter, hemolysis and kidney function were compared between 6 patients treated before and 14 patients treated after inclusion in our setup of extracorporeal membrane oxygenation with a servo inlet pressure regulator. RESULTS: In vitro, negative inlet pressure caused substantial hemolysis, leukocyte and platelet destruction, and complement activation. Maximal plasma free hemoglobin concentrations were 199 mg/100 mL before use of the servo inlet pressure regulator and 40 mg/100 mL afterward (p = 0.06), and serum creatinine peaked at 330 and 115 mumol/L, respectively (p = 0.03). The minimal 24-hour diuresis normalized for weight was 4.8 mL/kg before use of the servo inlet pressure regulator and 45.6 mL/kg afterward (p = 0.03). Three of 5 evaluable patients before use of the servo inlet pressure regulator and 1 of 14 patients after inclusion in this setup experienced anuria (p = 0.04). CONCLUSIONS: There were strong indications that reduction of negative pump inlet pressure with the servo regulator prevented hemolysis and kidney damage.

Effect of Diamphidia toxin, a Bushman arrow poison, on ionic permeability in nucleated cells.

The effect of Diamphidia toxin, isolated from pupae of Diamphidia nigro-ornata, was tested on two different cell lines (GH4C1 cells and HL-60 cells) and on human lymphocytes. The toxin raised intracellular Ca2+ concentration, as assessed with quin 2, in a dose-related manner in all three cell types. The effect was abolished when extracellular Ca2+ was chelated by EGTA. Low concentrations of the toxin evoked a delayed as well as a smaller response. The response time was also temperature-dependent, with a Q10 of about 2. Low, but effective concentrations of the toxin did not affect cell membrane integrity, as tested with Trypan blue, and induced a seemingly physiological release of prolactin from the GH4C1 cells. Diamphidia toxin's effect on the membrane permeability of GH4C1 cells was further investigated with patch-clamp techniques. The toxin appeared to increase the conductance for all small ions without affecting the normal ionic channels present in these cells. We conclude that Diamphidia toxin has a general effect on the plasma membrane of different cell types and thereby increases, probably non-specifically, the permeability for small ions.

Extracorporeal membrane oxygenation support for 59 days without changing the ECMO circuit: a case of Legionella pneumonia.

We report the successful use of veno-venous extracorporeal membrane oxygenation (ECMO) in a 53-year-old patient with Legionella pneumonia and acute respiratory distress syndrome (ARDS) with severe barotraumas. The patient was supported for 59 days without any changes in the ECMO circuit. This is probably the longest support ever reported using the same oxygenator.

Is it possible to predict outcome in pulmonary ECMO? Analysis of pre-operative risk factors.

Serious pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO) when other treatment has failed. The aim of this study was to analyze pre-operative risk factors of early mortality in patients who underwent either veno-arterial (VA) ECMO or veno-venous (VV) ECMO for pulmonary failure. We studied a total of 26 risk factors in 72 patients with severe pulmonary insufficiency treated with ECMO. All consecutive cases treated at our institution between Sept 1990 and Aug 2007 were included. Univariate analysis and multiple logistic regression analysis were performed on 26 risk factors. The end point was early mortality (any death within 30 days of ECMO treatment). Thirty-six (50%) of the patients died within 30 days of treatment. Age, gender, body mass index(BMI)(adults), cause of pulmonary failure, pre-ECMO treatment with nitric oxide(NO), intra-aortic balloon pump(IABP), and type of ventilation did not significantly influence early mortality. Neither pre-operative blood gas results, oxygenation index or pre-operative PaO(2)/FiO(2) ratio, nor mean ventilator days prior to ECMO gave any indications on early mortality. Liver function did not predict early mortality, but pre-ECMO serum creatinine levels were significantly lower in patients who survived. Treatment with ECMO in patients with severe pulmonary failure may save lives. It is, however, difficult to predict outcome when initiating ECMO. In this analysis, only pre-operative serum creatinine levels correlated with survival. None of the other parameters, including those which were used to select patients for ECMO treatment, could significantly predict the outcome.

Transportation of critically ill patients on extracorporeal membrane oxygenation.

Serious pulmonary and cardiac failure may be treated with extracorporeal membrane oxygenation (ECMO) when conventional treatment fails. In some severely ill patients, it may be necessary to initiate ECMO at the local hospital and, thereafter, transport the patient back to the ECMO center. The aim of this study was to evaluate our experiences with transportation of patients on ECMO. From Oct 1992 to Jan 2008 23, patients were transported on ECMO from local hospitals to Rikshospitalet. The study included seventeen patients with pulmonary failure and four patients with cardiac failure. All age groups were represented. Aircraft were used in 17 cases, ground vehicles in six. The times from decision until ECMO was established, the time from ECMO to departure from the local hospital and the transportation time were registered. All transportations were uneventful. After 10.3 +/-6.7 days, six patients died on ECMO and another patient died within 30 days. Mean ECMO time for those who died was 13.3 +/- 9.6 vs. 8.5 +/- 4.7 days for survivors, p=0.34. Seventeen patients were able to be successfully weaned from ECMO. Thirty day survival was 67%. The mean age for survivors was 15.3+/-18.3 (range 0-54.6) vs. 23.6 +/- 20.3 years (range 0-55.9) in fatal cases, p=0.41. The time from referral to initiating ECMO was a mean of 7.32 +/- 2.3 (3.0-12.0) hours for survivors vs. 7.88 +/- 3.0 (3.50-13.40) hours for non- survivors, p=0.76. The time from initiating ECMO to departure was 5.1 +/- 6.5 (0.58-23.75) hours in survivors vs. 9.1 +/- 6.8 (0.55-18.45) hours in non-survivors, p=0.18. Time from departure to arrival at Rikshospitalet was a mean of 3.2 (0.50-5.10) hours for survivors versus 2.5 (0.5-4.40) for non-survivors, p=0.41. This study shows that ECMO can be successfully established at local hospitals, using an experienced team, and that transportation of patients on ECMO can be performed safely and without technical difficulties. Survival for this group of patients did not differ from patients treated at the ECMO center.

Evaluation of oxygenators and centrifugal pumps for long-term pediatric extracorporeal membrane oxygenation.

OBJECTIVE: Two extracorporeal membrane oxygenation (ECMO) circuits for children under 10 kg were evaluated and compared for plasma leakage, hemolysis, blood transfusions, and durability. METHODS: Group A (n=20) was supported by ECMO circuits with the Minimax oxygenator and the Biomedicus centrifugal pump. Group B (n=10) was supported by ECMO circuits with the Lilliput 2 ECMO oxygenator and the Rotaflow centrifugal pump. RESULTS: ECMO circuit durability, as measured by oxygenator lifespan, was significantly better in Group B than in Group A (p = 0.04). There was significantly lower hemolysis, measured by plasma free hemoglobin, in Group B (p = 0.019), and patients in Group B had significantly less need for antithrombin III transfusion (p = 0.004). No plasma leakage was observed in Group B oxygenators, but plasma leakage was observed in all Group A oxygenators. CONCLUSION: The combination of a Rotaflow centrifugal pump and Lilliput 2 ECMO oxygenator in pediatric ECMO circuits improved durability and reduced circuit-induced hemolysis. This improvement may be due to the low priming volume, the oxygenator's plasma leakage resistance, the suspended rotor of the centrifugal pump, or a combination of these factors.

Detection of infrasound and linear acceleration in fishes.

Fishes have an acute sensitivity to extremely low-frequency linear acceleration, or infrasound, even down to below 1 Hz. The otolith organs are the sensory system responsible for this ability. The hydrodynamic noise generated by swimming fishes is mainly in the infrasound range, and may be important in courtship and prey predator interactions. Intense infrasound has a deterring effect on some species, and has a potential in acoustic barriers. We hypothesize that the pattern of ambient infrasound in the oceans may be used for orientation in migratory fishes, and that pelagic fishes may detect changes in the surface wave pattern associated with altered water depth and distant land formations. We suggest that the acute sensitivity to linear acceleration could be used for inertial guidance, and to detect the relative velocity of layered ocean currents. Sensitivity to infrasound may be a widespread ability among aquatic organisms, and has also been reported in cephalopods and crustaceans.

Detection of infrasound by the Atlantic cod.

Below about 50 kHz the level of ambient noise in the sea increases continuously towards lower frequencies. In the infrasound range the spectral slope is particularly steep. This low-frequency noise may propagate long distances with little attenuation, causing a directional pattern of infrasound in the sea. Using a standing-wave acoustic tube, we have studied the sensitivity of cod to infrasound down to 0.1 Hz by means of the cardiac conditioning technique. The threshold values, measured as particle acceleration, showed a steady decline towards lower frequencies below 10 Hz, reaching a value close to 10(-5)ms-2 at 0.1 Hz. The spectrum level at 0.1 Hz in the sea ranges between 120 and 180 dB (re 1 microPa), with corresponding particle accelerations from less than 10(-6) to more than 10(-4)ms-2. The sensitivity of cod is thus sufficient to detect the highest levels of ambient infrasound, and we put forward the hypothesis that fish may utilize information about the infrasound pattern in the sea for orientation during migration, probably in addition to an array of other sensory inputs.

Response to rates of luminance change of sustained and transient cells in the cat lateral geniculate nucleus and optic tract.

We recorded the response of sustained (X) and transient (Y) cells in the cat lateral geniculate nucleus (LGN) and optic tract to a stationary spot while the spot luminance was increased and decreased with a constant rate (linear luminance functions), or modulated sinusoidally. The spot filled the receptive field center, and was surrounded by an annulus of fixed luminance. The LGN X cells seemed to perform a differentiation-like operation in the time domain at slow temporal modulations, giving information about rate of luminance change. To the linear luminance functions the cells responded with a constant firing rate. The on-center cells were activated during increasing luminance, the off-center cells during decreasing luminance. This firing rate increased monotonically with rate of luminance change. To low-frequency sinusoidal modulations the cells had a marked negative phase shift. The response of the LGN Y cells had a transient component shortly after the luminance started to increase (on-center cells) or decrease (off-center cells), followed by a secondary, gradually changing component. The peak of the transient component occurred on average when the response of the X cells increased most rapidly. To low-frequency sinusoidal modulation the average negative phase shift of this peak was twice the average of the X cells. The Y system could accordingly provide information about rate of change in the response of the X system. In the optic tract the X fiber response resembled the LGN X cell response in most respects. The Y fibers had only a weak transient response component, so this component was accentuated in the thalamic relay. Also the sensitivity for rate of luminance change was increased in LGN.

Vasoactive intestinal peptide (VIP) may reduce the removal rate of cytosolic Ca2+ after transient elevations in clonal rat lactotrophs.

The prolactin-producing rat anterior pituitary GH4C1 cells possess Ca2+-activated K channels which are activated by physiological elevations of the cytosolic Ca2+ concentration even at membrane potentials more negative than the normal level of about -50 mV. Whole-cell current recordings showed a marked outward tail current following depolarizing voltage steps to 0 mV from a holding potential close to the normal membrane potential. The half-time of this tail current was about 1.3 s after a 4-s depolarization step. The GH4C1 cells also possess voltage-activated Ca channels, and we conclude that this tail current is a Ca2+-activated K+ current for the following reasons: (1) The reversal potential for the tail current was close to the K+ equilibrium potential for a range of transmembrane K+ gradients. (2) The tail current was blocked by a Ca2+ antagonist, and the voltage dependence of this current closely mirrored the voltage dependence of the isolated Ca2+ current. The time-course of the decline of the tail current thus reflects the removal rate of the Ca2+ entering the cytosol through voltage-dependent Ca channels during the depolarizing voltage step. VIP stimulates prolactin secretion from GH4C1 cells, and this peptide prolonged the half-time of the tail current by about 47% in 63% of the cells. This indicates that VIP may prolong the transient cytosolic Ca2+ elevations following the action potentials in these cells. Such a mechanism might be an important factor for the control of the cytosolic Ca2+ level, and hence hormone secretion.

[From a registry to a clinical information system. Development of the Datacor system at the surgery department A, Rikshospitalet]. / Fra virksomhetsregistrering til klinisk informasjonssystem. Utvikling av Datacor-systemet ved Kirurgisk avdeling A, Rikshospitalet.

Based on a simple register for thoracic and cardiovascular operations a modulated system has been built up at Department of Surgery A. The register covers waiting list, a basic patient record, extensive operative data, the postoperative course and the final outcome. A local area network includes 36 microcomputers with approximately 75 users. Owing to lack of commercially available programs, local applications based on dBase have been developed. In this article we discuss our positive experiences from use of the local system with respect to administration, quality assurance and local research, its future place within a larger hospital system interconnected via a backbone, the need for better support and graphic user interface.

Comparison of bubble release from various types of oxygenators. An in vivo investigation.

The present study compares the creation of free gas bubbles in five different bubble oxygenators and one membrane oxygenator, by use of Doppler ultrasound technique. The study was carried out on groups of male patients undergoing coronary artery bypass surgery. The results show that the bubble oxygenators produce a considerable amount of free gas bubbles, with variances based on type. The membrane oxygenator showed virtually no counts at all.

Different-sized mRNAs from GH4C1 cells induce a TRH-dependent electrical response in Xenopus laevis oocytes.

Poly(A)+ RNA from the GH4C1 rat pituitary cell line elicited a thyrotropin releasing hormone response in Xenopus laevis oocytes which could be measured as a change in membrane current by the voltage-clamp method. Oocytes injected with Poly(A)+ RNA from GH12C1 cells which do not bind thyrotropin releasing hormone or with buffer solution alone did not show this response. Size fractionation of total poly(A)+ RNA by sucrose density-gradient centrifugation shows two response maximal representing various mRNA fractions larger than 18S. These results indicate the presence of thyrotropin releasing hormone receptor mRNA heterogeneity where the smallest mRNA is at least 2 kb.