Assessment of a Bayesian Vitrea CT Perfusion Analysis to Predict Final Infarct and Penumbra Volumes in Patients with Acute Ischemic Stroke: A Comparison with RAPID.

BACKGROUND AND PURPOSE: Brain CTP is used to estimate infarct and penumbra volumes to determine endovascular treatment eligibility for patients with acute ischemic stroke. We aimed to assess the accuracy of a Bayesian CTP algorithm in determining penumbra and final infarct volumes. MATERIALS AND METHODS: Data were retrospectively collected for 105 patients with acute ischemic stroke (55 patients with successful recanalization [TICI 2b/2c/3] and large-vessel occlusions and 50 patients without interventions). Final infarct volumes were calculated using DWI and FLAIR 24 hours following CTP imaging. RAPID and the Vitrea Bayesian CTP algorithm (with 3 different settings) predicted infarct and penumbra volumes for comparison with final infarct volumes to assess software performance. Vitrea settings used different combinations of perfusion maps (MTT, TTP, CBV, CBF, delay time) for infarct and penumbra quantification. Patients with and without interventions were included for assessment of predicted infarct and penumbra volumes, respectively. RESULTS: RAPID and Vitrea default setting had the most accurate final infarct volume prediction in patients with interventions ([Spearman correlation coefficient, mean infarct difference] default versus FLAIR: [0.77, 4.1 mL], default versus DWI: [0.72, 4.7 mL], RAPID versus FLAIR: [0.75, 7.5 mL], RAPID versus DWI: [0.75, 6.9 mL]). Default Vitrea and RAPID were the most and least accurate in determining final infarct volume for patients without an intervention, respectively (default versus FLAIR: [0.76, -0.4 mL], default versus DWI: [0.71, -2.6 mL], RAPID versus FLAIR: [0.68, -49.3 mL], RAPID versus DWI: [0.65, -51.5 mL]). CONCLUSIONS: Compared with RAPID, the Vitrea default setting was noninferior for patients with interventions and superior in penumbra estimation for patients without interventions as indicated by mean infarct differences and correlations with final infarct volumes.

Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response.

BACKGROUND: Porcine small intestinal submucosa (SIS) is an acellular, naturally derived extracellular matrix (ECM) that has been used for tissue remodeling and repair in numerous xenotransplantations. Although a vigorous immune response to xenogeneic extracellular matrix biomaterials is expected, to date there has been evidence for only normal tissue regeneration without any accompanying rejection. The purpose of this study was to determine the reason for a lack of rejection. METHODS: Mice were implanted s.c. with xenogeneic tissue, syngeneic tissue, or SIS, and the graft site analyzed histologically for rejection or acceptance. Additionally, graft site cytokine levels were determined by reverse transcriptase polymerase chain reaction and SIS-specific serum antibody isotype levels were determined by ELISA. RESULTS: Xenogeneically implanted mice showed an acute inflammatory response followed by chronic inflammation and ultimately graft necrosis, consistent with rejection. Syngeneically or SIS implanted mice, however, showed an acute inflammatory response that diminished such that the graft ultimately became indistinguishable from native tissue, observations that are consistent with graft acceptance. Graft site cytokine analysis showed an increase in interleukin-4 and an absence of interferon-gamma. In addition, mice implanted with SIS produced a SIS-specific antibody response that was restricted to the IgG1 isotype. Reimplantation of SIS into mice led to a secondary anti-SIS antibody response that was still restricted to IgG1. Similar results were observed with porcine submucosa derived from urinary bladder. To determine if the observed immune responses were T cell dependent, T cell KO mice were implanted with SIS. These mice expressed neither interleukin-4 at the implant site nor anti-SIS-specific serum antibodies but they did accept the SIS graft. CONCLUSIONS: Porcine extracellular matrix elicits an immune response that is predominately Th2-like, consistent with a remodeling reaction rather than rejection.

Head-to-cervix force: an important physiological variable in labour. 1. The temporal relation between head-to-cervix force and intrauterine pressure during labour.

OBJECTIVE: To investigate the relation between the rise in intrauterine pressure and rise in fetal head to cervix force in normal, slow and induced labour. DESIGN: Prospective observational study. SETTING: The labour ward of a London teaching hospital. PARTICIPANTS: Forty patients were recruited from the antenatal clinic and labour ward of a West London Hospital. Five had normal onset and progression of labour, 14 had slow progression of labour and 21 had induced onset of labour. METHOD: Intrauterine pressure and head-to-cervix force was measured simultaneously using an intrauterine pressure catheter and a specially designed four sensor head-to-cervix force probe. RESULTS: For each contraction of each labour, scattergrams of force by pressure were plotted. Three patterns were observed. When the rise in pressure preceded the rise in force, a positive 'loop' was generated. When the rise in pressure and force occurred simultaneously a linear pattern was generated (a neutral 'loop'). When the rise in pressure lags the rise in force, a negative 'loop' was generated. In normally progressive labour the distribution of loops was 29.1%, 22.6% and 48.3%, respectively, in slow labour the distribution was 26.1%, 14.1% and 59.8% and in induced labour the distribution was 33.8%, 14.4% and 51.8%. These distributions were not statistically different. However, a higher proportion of negative loops was observed in labours augmented with oxytocin compared to those receiving no oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity, use of PGE2, epidural analgesia, or mode of delivery. Contraction frequency (number/10 minutes) was inversely correlated to the percentage of negative loops (rs = -0.34, P = 0.033) and positively correlated with percentage of positive loops (rs = 0.36, P = 0.027). CONCLUSIONS: This is the first report of the temporal relation between intrauterine pressure and head-to-cervix force in labour. The most common pattern is that the rise in pressure lags the rise in force, suggesting that a seal has to be created between the fetal head and cervix before a rise in pressure can occur. When oxytocin is given in labour, a higher proportion of loops are negative indicating that there is poor application of the fetal head and cervix in a greater proportion of contractions.

Head-to-cervix force: an important physiological variable in labour. 2. Peak active force, peak active pressure and mode of delivery.

OBJECTIVE: To assess the relation between peak active (above baseline) head-to-cervix force (paHCF) and peak active (above baseline) intrauterine pressure (paIUP) in labour, and to compare the relation between labours progressing well and ending in vaginal delivery and those labours progressing slowly and ending in caesarean section. DESIGN: Prospective observational study. SETTING: The labour ward of a London teaching hospital. PARTICIPANTS: Forty women in labour who agreed to have an experimental head-to-cervix force probe and an intrauterine pressure catheter inserted. RESULTS: The relation was linear, with a correlation coefficient which ranged from 0.012 to 0.885 (mean value 0.438). The closeness of the relation did not correlate with the rate of cervical dilatation (r = 0.0192, P = 0.574) or the mode of delivery (r = 0.215, P = 0.183). However, in women who progressed well to a vaginal delivery, the mean slope of the paHCF to paIUP regression line was 0.72, significantly steeper than in women who progressed slowly and required delivery by caesarean section (mean slope = 0.45, t = 2.31, P = 0.02). Mean paIUPs were significantly higher in women progressing well and achieving a vaginal delivery than in those progressing slowly and requiring caesarean section (45.3 mmHg SD 7.5 vs 38.4 mmHg SD 11.4, t = 2.31, P = 0.02), but the overlap between the two groups was considerable. However, in keeping with their steeper paHCF/paIUP slope, women progressing well to a vaginal delivery had substantially higher head-to-cervix forces (46.4 gWt SD 11.8 vs 28.3 gWt SD 8.2, t = 5.22, P < 0.00001) than those progressing slowly and requiring caesarean section, and there was much less overlap between paHCF than paIUP. This resulted in paHCF being a much better discriminating variable than paIUP for mode of delivery. CONCLUSIONS: The relation between paHCF and paIUP is linear, but there is a wide variation in the degree of correlation between one woman and another. Women with a steep slope of paHCF relative to paIUP are more likely to achieve a high mean paHCF, progress rapidly in labour and achieve a vaginal delivery than women with a flap slope, although mean paIUPs do not differ substantially between the two groups. The level of paHCF was substantially better than cervical dilatation rate at predicting mode of delivery. These results suggest that head-to-cervix force is sensitive to factors determining mode of delivery which are not reflected in either the level of uterine activity as measured by intrauterine pressure, or cervical compliance as measured by cervical dilatation rates.

Superovulation, IGFBP-1 and birth weight.

In this study, the effect of superovulation on the circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) has been investigated. IGFBP-1 levels were measured in singleton pregnancies achieved either naturally (n = 203) or following superovulation, in-vitro fertilisation and embryo transfer (IVF-ET) with either pituitary desensitisation with buserelin and superovulation with human menopausal gonadotrophin (b/hMG) followed by IVF-ET (n = 15) or with clomiphene citrate and hMG (CC/hMG) followed by IVF-ET (n = 15, 1st trimester only). The circulating levels of IGFBP-1 were similar in all three groups during the first trimester, and in both normal and b/hMG pregnancies in the second, but were significantly higher during the third trimester in b/hMG pregnancies than in normal pregnancies (P = 0.0002). The birth weights were significantly lower in the b/hMG group (P = 0.04), but not in the CC/hMG group compared with natural conceptions. Gestational age at delivery was similar in control and b/hMG pregnancies, but significantly reduced in CC/hMG pregnancies (P = 0.04). These data suggest that pregnancies achieved following superovulation with b/hMG are associated with elevated levels of IGFBP-1 during the third trimester of pregnancy and reduced birth weight.

A Microsoft Windows based application for acquisition and replay of cardiotocograph data.

The electronic fetal monitor or cardiotocograph is an integral part of all modern labour wards. It records fetal heart and uterine contractions and charts this data as a cardiotocogram (CTG). The CTG is used to assess fetal well-being by the labour attendants and in some circumstances for research. A means to acquire and display the CTG by microcomputer as an aid to archiving and to obstetric research is presented. A Microsoft Windows-based application was written using Microsoft C version 7.0 to acquire and replay the CTG data. The application acquires the CTG data by using the RS232 serial link fitted on most modern fetal monitors. Additionally, comments and events can be entered by the user throughout recording. The data are saved to disk files which can be replayed on screen in the manner of a CTG. The data replay functions of the application calculates the uterine activity integral and active pressure for each contraction and for 15 min intervals. This calculated data is not available from many fetal monitors but is widely used for research into the mechanics of labour. This application provides an easy, reliable and accurate means of acquiring the CTG data, for archiving and research. It also provides a framework for further CTG analysis.

The regulation of plasma relaxin levels during human pregnancy.

The factors that determine the circulating levels of relaxin during pregnancy have been investigated by comparing the plasma levels of relaxin throughout pregnancy in women who became pregnant spontaneously (singleton, n = 240) or following superovulation (singleton and multifetal pregnancies (two to ten conceptuses), n = 83). Some of the women with multifetal pregnancies underwent selective fetal reduction to twin pregnancies. Relaxin levels were higher at 7-34 weeks of gestation in singleton pregnancies achieved following superovulation when compared with levels in spontaneously conceived singleton pregnancies (p < 0.05-0.001). In samples obtained between 10 and 12 weeks of gestation (before fetal reduction for the multifetal pregnancies), plasma relaxin levels correlated with fetal number (r = 0.526, P = 0.0001). Reduction in fetal number to a twin pregnancy did not alter relaxin levels. These data suggest that the circulating levels of relaxin throughout pregnancy are determined during the cycle of conception by gonadotrophin stimulation, and within the first 10 weeks of pregnancy by the luteotrophic stimulus from the conceptus. Furthermore, once corpus luteum synthesis of relaxin is established, then reduction in the luteotrophic stimulus does not appear to affect it.

Monitoring uterine activity.

Uterine activity may be monitored by methods ranging from gentle palpation of the uterine fundus to the most sophisticated electronic intrauterine pressure monitoring system. The form of monitoring required depends largely on the clinical situation. The relationship between fetal oxygenation and uterine contractions has ensured the continued place of cardiotocographic monitoring.

Is obstetric and neonatal outcome worse in fetuses who fail to reach their own growth potential?

OBJECTIVES: To determine the perinatal outcome of fetuses who had birthweights less than that expected from early third trimester ultrasound scanning. DESIGN: Retrospective estimation of centile fetal weight at early third trimester ultrasound scanning compared with actual centile birthweight corrected for gestational age, parity and sex. SETTING: Teaching Hospital Obstetric Unit, London. SUBJECTS: 197 unselected women with singleton cephalic pregnancies who were delivered at term in our unit between October 1989 and May 1990. MAIN OUTCOME MEASURES: CTG abnormality, need for fetal blood sampling in labour, meconium-staining of the amniotic fluid, mode of delivery, Apgar scores at 1 and 5 min, need for transfer of baby to neonatal unit, and need for neonatal intubation of the neonate at delivery. RESULTS: An actual birthweight greater than 5% less than the birthweight estimated from ultrasound scanning identified 44 babies (22%) with an increased risk of CTG abnormalities (chi 2 = 8.38, P less than 0.0025; Odds ratio (OR) = 2.54; 95% CI 1.36 to 4.78) and need for operative delivery (chi 2 = 5.81, P less than 0.0125; OR = 1.94; 95% CI 1.15 to 3.27), when compared with the remainder of the sample. Overall 14 (32%) of this group had birthweights above the 50th centile. A group of 44 babies selected as being the smallest for gestational age, without reference to growth pattern, had a similar excess morbidity. (All this group had birthweights below the 39th centile). CONCLUSIONS: This study supports the hypothesis that in-utero fetal growth pattern is as important for perinatal outcome as being small for gestational age per se.

The psychic costs of intense positive affect.

Recent research indicates that happiness, or affective well-being, is related primarily to the frequency, not to the intensity, of positive affect (PA). The question arises as to why intense positive affect (PI) is not a larger contributor to subjective well-being. Whether processes that yield PI also produce intense negative affect was examined. Studies 1 and 2 suggested that cognitive mechanisms that amplify or dampen affect can carry over from positive to negative events. Study 3 demonstrated that, because of judgment mechanisms, an extremely positive event can make other events less positive. Study 4 revealed that naturally occurring intensely positive experiences are often preceded by negative ones. Study 5 suggested that the more persons valence success at a task, the happier they will be if they succeed, but unhappier if they fail. The 5 studies reveal that intense positive experiences may sometimes have costs that counterbalance their desirable nature.

Relaxin levels in ovum donation pregnancies.

STUDY OBJECTIVE: To investigate the relative contributions of the corpus luteum (CL) and the placenta to the circulating levels of relaxin during pregnancy. PATIENTS: Forty-one patients in whom pregnancy had been achieved by ovum donation. RESULTS: Relaxin was not detected in the serum of 36 patients; in the remaining 5, although it was detectable, the levels were markedly reduced when compared with those in normal pregnancies. CONCLUSION: These results demonstrate that the CL is essential for the maintenance of normal circulating levels of relaxin during pregnancy.