Assessing the accuracy of systolic aortic pressure estimation from a brachial cuff alone: a comparison with radial tonometry.

BACKGROUND: A novel method for estimating central systolic aortic pressure (cSAP) has emerged, relying solely on peripheral mean (MBP) and diastolic (DBP) blood pressures. We aimed to assess the accuracy of this Direct Central Blood Pressure estimation using cuff alone (DCBPcuff=MBP²/DBP) in comparison to the use of generalized transfer function to derive cSAP from radial tonometry (cSAPtono). METHODS: This retrospective analysis involved International Database of Central Arterial properties for Risk Stratification (IDCARS) data (Aparicio et al., Am J Hypertens 2022). The dataset encompassed 10,930 subjects from 13 longitudinal cohort studies worldwide (54.8%women; median age 46.0 years; office hypertension: 40.1%; treated: 61.0%), documenting cSAPtono via SphygmoCor calibrated against brachial systolic BP (SBP) and DBP. Our analysis focused on aggregate group data from 12/13 studies (89%patients) where full BP dataset was available. A 35% form factor was used to estimate MBP = (DBP+(0.35×(SBP-DBP)), from which DCBPcuff was derived. The predefined acceptable error for cSAPtono estimation was set at ≤5mmHg. RESULTS: The cSAPtono values ranged 103.8-127.0 mmHg (n=12). The error between DCBPcuff and cSAPtono was 0.2 ± 1.4 mmHg, with no influence of the mean. Errors ranged from -1.8 to 2.9 mmHg across studies. No significant difference in errors was observed between BP measurements obtained via oscillometry (n=9) vs auscultation (n=3) (p=0.50). CONCLUSIONS: Using published aggregate group data and a 35% form factor, DCBPcuff demonstrated remarkable accuracy in estimating cSAPtono, regardless of the BP measurement technique. However, given that individual BP values were unavailable, further documentation is required to establish DCBPcuff's precision.

The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis.

OBJECTIVE: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. METHODS: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. RESULTS: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). CONCLUSIONS: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Maternal and fetal characteristics for predicting risk of Cesarean section following induction of labor: pooled analysis of PROBAAT trials.

OBJECTIVE: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one-fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS. METHODS: This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non-linear relationship with outcome. Optimal cut-offs for those characteristics with a non-linear pattern were determined based on the maximum area under the receiver-operating-characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome. RESULTS: Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31-35 years compared with younger women (aOR, 1.51 (95% CI, 1.15-1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34-12.18)) and in Sub-Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33-3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04-1.08)). High birth-weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74-4.07) for birth weight between the 80.0th and 89.9th percentiles and aOR, 4.08 (95% CI, 2.75-6.05) for birth weight ≥ 90th percentile, as compared with birth weight between the 20.0th and 49.9th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05-1.12)) and BMI (aOR, 1.05 (95% CI, 1.03-1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76-9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23-5.10)). Birth weight < 10.0th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22-3.05)), as compared with birth weight between the 20.0th and 49.9th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC. CONCLUSIONS: In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth-weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Induction of labor with Foley catheter and risk of subsequent preterm birth: follow-up study of two randomized controlled trials (PROBAAT-1 and -2).

OBJECTIVE: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. METHODS: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy. RESULTS: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51). CONCLUSION: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Norepinephrine exerts an inotropic effect during the early phase of human septic shock.

BACKGROUND: We conducted this study to investigate whether norepinephrine increases cardiac contractility when administered during the early phase of septic shock. METHODS: We studied 38 patients with septic shock who had been resuscitated for <3 h and whose mean arterial pressure (MAP) remained <65 mm Hg. Echocardiographic variables were obtained before (T0) and after either initiation or an increase in the dose of a norepinephrine infusion to increase MAP to ≥ 65 mm Hg (T1). We collected left ventricular ejection fraction (LVEF), velocity-time integral of the left ventricular outflow tract (VTI), tissue Doppler imaging of mean systolic velocity of the lateral tricuspid annulus (Sa) and of the lateral mitral annulus (Sm), and tricuspid annular plane systolic excursion (TAPSE). RESULTS: There were significant (P<0.05) increases from T0 to T1 in MAP [mean (sd): from 56 (7) to 80 (9) mm Hg], LVEF [from 49 (13) to 56 (13)%], VTI [from 18 (5) to 20 (6) cm], Sm [from 10.8 (5.1) to 12.1 (5.0) cm s-1], TAPSE [from 1.8 (0.5) to 2.0 (0.5) cm], and Sa [from 13.0 (5.6) to 15.1 (6.4) cm s-1]. In the subgroup of 15 patients with LVEF ≤45%, significant increases in VTI [from 16 (8) to 18 (7) cm] and in LVEF [from 36 (7) to 44 (10)%] were observed. CONCLUSIONS: Norepinephrine administration during early resuscitation in patients with septic shock increased the cardiac systolic function despite the presumed increase in left ventricular afterload secondary to the increased arterial pressure. Whether such an effect persists over time remains to be evaluated. CLINICAL TRIAL REGISTRATION: NCT02750683.

Comparing induction of labour with oral misoprostol or Foley catheter at term: cost-effectiveness analysis of a randomised controlled multi-centre non-inferiority trial.

OBJECTIVE: To assess the costs of labour induction with oral misoprostol versus Foley catheter. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of six tertiary and 23 secondary care hospitals in the Netherlands. POPULATION: Women with a viable term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix (Bishop score <6) without a previous caesarean section, were randomised for labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921). METHODS: We performed economic analysis from a hospital perspective. We estimated direct medical costs associated with healthcare utilisation from randomisation until discharge. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per women induced with oral misoprostol or Foley catheter. RESULTS: Mean costs per woman in the oral misoprostol group and Foley catheter group were €4470 versus €4158, respectively [mean difference €312, 95% confidence interval (CI) -€508 to €1063]. Multiple sensitivity analyses did not change these conclusions. However, if cervical ripening for low-risk pregnancies in the Foley catheter group was carried out in an outpatient setting, with admittance to labour ward only at start of active labour, the difference would be €4470 versus €3489, respectively (mean difference €981, 95% CI €225-1817). CONCLUSIONS: Oral misoprostol and Foley catheter generate comparable costs. Cervical ripening outside labour ward with a Foley catheter could potentially save almost €1000 per woman. TWEETABLE ABSTRACT: Oral misoprostol or Foley catheter for induction of labour generates comparable costs.

Avascular necrosis as a complication of the treatment of dislocation of the hip in children with cerebral palsy.

We investigated the incidence and risk factors for the development of avascular necrosis (AVN) of the femoral head in the course of treatment of children with cerebral palsy (CP) and dislocation of the hip. All underwent open reduction, proximal femoral and Dega pelvic osteotomy. The inclusion criteria were: a predominantly spastic form of CP, dislocation of the hip (migration percentage, MP > 80%), Gross Motor Function Classification System, (GMFCS) grade IV to V, a primary surgical procedure and follow-up of > one year. There were 81 consecutive children (40 girls and 41 boys) in the study. Their mean age was nine years (3.5 to 13.8) and mean follow-up was 5.5 years (1.6 to 15.1). Radiological evaluation included measurement of the MP, the acetabular index (AI), the epiphyseal shaft angle (ESA) and the pelvic femoral angle (PFA). The presence and grade of AVN were assessed radiologically according to the Kruczynski classification. Signs of AVN (grades I to V) were seen in 79 hips (68.7%). A total of 23 hips (18%) were classified between grades III and V. Although open reduction of the hip combined with femoral and Dega osteotomy is an effective form of treatment for children with CP and dislocation of the hip, there were signs of avascular necrosis in about two-thirds of the children. There was a strong correlation between post-operative pain and the severity of the grade of AVN.

Comparison of pulse contour analysis by Pulsioflex and Vigileo to measure and track changes of cardiac output in critically ill patients.

BACKGROUND: We compared the new Pulsioflex and the Vigileo devices to measure cardiac index (CI) in critically ill patients. Both devices measure CI by pulse-contour analysis. The Pulsioflex device also allows an auto-calibration (not based on thermodilution). METHODS: Patients were included if we administered fluids (20 patients), reduced (20 patients), or increased (20 patients) the dose of norepinephrine. Before and after interventions, we measured CI provided by the Vigileo (CIVig) and Pulsioflex (CIPfx) devices before and after its auto-calibration. CI measured by transpulmonary thermodilution (CIthermo) was used as the reference. RESULTS: Considering absolute values of CI (n=120), the percentage error was 59% for CIVig vs CIthermo and 40% for CIthermo vs CIPfx. Auto-calibrating CIPfx after interventions did not improve the percentage error between CIPfx and CIthermo (39%). Considering the fluid-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.50 for CIVig, and 0.73 for CIPfx (P=0.27). It was not significantly improved if CIPfx was auto-calibrated (r=0.64). Considering the norepinephrine-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.41 for CIVig. It tended to be better for CIPfx (r=0.71, P=0.07). It was not significantly improved by auto-calibration (r=0.53). CONCLUSIONS: The Pulsioflex did not reliably estimate the absolute values of CI. For tracking fluid-induced changes in CI, the Pulsioflex was reliable, and also the Vigileo. For tracking norepinephrine-induced changes in CI, it was also reliable and tended to be better than the Vigileo. Auto-calibration allowed by the system did not improve its reliability.

Assessment of changes in left ventricular systolic function with oesophageal Doppler.

BACKGROUND: We tested the ability of mean acceleration (Acc) and peak velocity (V peak) of the aortic velocity signal measured by oesophageal Doppler to reflect left ventricular (LV) systolic performance. METHODS: We included critically ill patients in whom a fluid challenge (n=25) or the introduction of dobutamine, 5 µg kg(-1) min(-1) (n=25), was planned by the attending physician. Before and after therapeutic interventions, we measured Acc and V peak (CardioQ device) and LV ejection fraction (LVEF) using echocardiography. RESULTS: For all pairs of measurements, the absolute values of Acc and V peak correlated with LVEF (r=0.36 and 0.57, respectively). The correlation was significantly higher for V peak than for Acc. Volume expansion did not significantly change LVEF and Acc, but significantly increased V peak by 7 (8)%. Dobutamine increased LVEF by 30 (15)%, Acc by 33 (25)%, and V peak by 20 (10)%. Considering the pooled effects of volume expansion and dobutamine, changes in Acc and V peak and those of LVEF were correlated (r=0.53 and 0.67, respectively). When excluding changes <18% (i.e. the least significant change for LVEF), the concordance rate was 96% for Acc and 100% for V peak. CONCLUSIONS: V peak and, to a lesser extent, Acc measured by oesophageal Doppler behaved as markers of LV systolic performance as they were almost insensitive to fluid administration and changed to a much larger extent with dobutamine. These indices could be used to estimate LV systolic performance and to assess the effects of inotropic therapy.

Experimental infection of juvenile domestic and Canada geese with two different clades of H5N1 high pathogenicity avian influenza virus.

Eighteen-day-old domestic geese (Anser anser f. domestica) and 3-week-old Canada geese (Branta canadensis) were experimentally infected with 10(6) EID50/bird of H5N1 high pathogenicity avian influenza (HPAI) virus isolates belonging to clades 1 and 2.2. Clinical signs were observed in all of the groups and included listlessness, inappetence, marked incoordination, torticollis, paralysis and lethargy. Mortality reached 100% (Canada geese) and 40-50% (domestic geese). During necropsy, congestion and hemorrhagic lesions were most often observed. Histopathological lesions were located in multiple organs and included inflammatory and hemorrhagic changes and, in later stages, occurrences of necrosis. All of the tested organ samples collected between 3 and 8 days PI were found positive in rRT-PCR, but the highest concentration of RNA was found in the brain. The observed delayed onset of mortality and prolonged duration of the disease in young domestic geese may be related to numerous host and virus factors.

Cost-effectiveness of induction of labour at term with a Foley catheter compared to vaginal prostaglandin E2 gel (PROBAAT trial).

OBJECTIVE: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of one university and 11 teaching hospitals in the Netherlands. POPULATION: Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section. METHODS: Cost-effectiveness analysis from a hospital perspective. MAIN OUTCOME MEASURES: We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes. RESULTS: Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E2 gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction. CONCLUSIONS: Foley catheter and prostaglandin E2 labour induction generate comparable costs.

Pleth variability index is a weak predictor of fluid responsiveness in patients receiving norepinephrine.

BACKGROUND: In patients receiving an infusion of norepinephrine, the relationship between the amplitude of the oximeter plethysmographic waveform and stroke volume may be variable and quality of the waveform might be reduced, compared with patients not receiving norepinephrine. We assessed the reliability of the pleth variability index (PVI), an automatic measurement of the respiratory variation of the plethysmographic waveform, for predicting fluid responsiveness in patients receiving norepinephrine infusions. METHODS: We measured the response of cardiac index (transpulmonary thermodilution) to i.v. fluid administration in 42 critically ill patients receiving norepinephrine. Patients with arrhythmias, spontaneous breathing, tidal volume <8 ml kg(-1), and respiratory system compliance <30 ml cm H(2)O(-1) were excluded. Before fluid administration, we recorded the arterial pulse pressure variation (PPV) and pulse contour analysis-derived stroke volume variation (SVV, PiCCO2) and PVI (Masimo Radical-7). RESULTS: In seven patients, the plethysmographic signal could not be obtained. Among the 35 remaining patients [mean SAPS II score=77 (sd=17)], i.v. fluid increased cardiac index ≥15% in 15 'responders'. A baseline PVI ≥16% predicted fluid responsiveness with a sensitivity of 47 (inter-quartile range=21-73)% and a specificity of 90 (68-99)%. The area under the receiver operating characteristic curve was significantly lower for PVI [0.68 (0.09)] than for PPV and SVV [0.93 (0.06) and 0.89 (0.07), respectively]. Considering all pairs of measurements, PVI was correlated with PPV (r(2)=0.27). The fluid-induced changes in PVI and PPV were not significantly correlated. CONCLUSIONS: PVI was less reliable than PPV and SVV for predicting fluid responsiveness in critically ill patients receiving norepinephrine. In addition, PVI could not be measured in a significant proportion of patients. This suggests that PVI is not useful in patients receiving norepinephrine.

Avian influenza viruses in wild birds at the Jeziorsko reservoir in Poland in 2008-2010.

During a 3-year surveillance study for avian influenza virus (AIV) infections at the Jeziorsko reservoir in central Poland, 549 oropharyngeal or cloacal swabs from 366 birds of 14 species belonging to 3 orders (Anseriformes, Charadriiformes and Gruiformes) were tested. AIV was detected in 14 birds (3.8%): Common Teals (12x), Mallard (1x) and Garganey (1x). Three potentially dangerous H5 AIV were detected in Common Teals (2x) and Garganey (1x) but all of them revealed a low pathogenic pathotype. A unique cleavage site amino acid motif PQREIR*GLF was found in one H5 isolate from a Garganey.

Prediction of fluid responsiveness by a continuous non-invasive assessment of arterial pressure in critically ill patients: comparison with four other dynamic indices.

BACKGROUND: We evaluated the ability of an infrared photoplethysmography arterial waveform (continuous non-invasive arterial pressure, CNAP) to estimate arterial pulse pressure variation (PPV). We compared the ability of non-invasive PPV to predict fluid responsiveness with invasive PPV, respiratory variation of pulse contour-derived stroke volume, and changes in cardiac index induced by passive leg raising (PLR) and end-expiratory occlusion (EEO) tests. METHODS: We measured the responses of cardiac index (PiCCO) to 500 ml of saline in 47 critically ill patients with haemodynamic failure. Before fluid administration, we recorded non-invasive and invasive PPVs, stroke volume variation, and changes in cardiac index induced by PLR and by 15 s EEO. Logistic regressions were performed to investigate the advantage of combining invasive PPV, stroke volume variation, PLR, and EEO when predicting fluid responsiveness. RESULTS: In eight patients, CNAP could not record arterial pressure. In the 39 remaining patients, fluid increased cardiac index by ≥15% in 17 'responders'. Considering the 195 pairs of measurements, the bias (sd) between invasive and non-invasive PPVs was -0.6 (2.3)%. The areas under the receiver operating characteristic (ROC) curves for predicting fluid responsiveness were 0.89 (95% confidence interval, 0.78-1.01) for non-invasive PPV compared with 0.89 (0.77-1.01), 0.84 (0.70-0.96), 0.95 (0.88-1.03), and 0.97 (0.91-1.03) for invasive pulse pressure, stroke volume variations, PLR, and EEO tests (no significant difference). Combining multiple tests did not significantly improve the area under the ROC curves. CONCLUSIONS: Non-invasive assessment of PPV seems valuable in predicting fluid responsiveness.

Third-generation FloTrac/Vigileo does not reliably track changes in cardiac output induced by norepinephrine in critically ill patients.

BACKGROUND: The ability of the third-generation FloTrac/Vigileo software to track changes in cardiac index (CI) induced by volume expansion and norepinephrine in critically ill patients is unknown. METHODS: In subjects with circulatory failure, we administered volume expansion (20 subjects) and increased (20 subjects) or decreased (20 subjects) the dose of norepinephrine. We measured arterial pressure waveform-derived CI provided by the third-generation FloTrac/Vigileo device (CI(pw)) and transpulmonary thermodilution CI (CI(td)) before and after therapeutic interventions. RESULTS: Considering the pairs of measurements performed before and after all therapeutic interventions (n=60), a bias between the absolute values of CI(pw) and CI(td) was 0.26 (0.94) litre min(-1) m(-2) and the percentage error was 54%. Changes in CI(pw) tracked changes in CI(td) induced by volume expansion with moderate accuracy [n=20, bias=-0.11 (0.54) litre min(-1) m(-2), r(2)=0.26, P=0.02]. When changes in CI(td) were induced by norepinephrine (n=40), a bias between CI(pw) and CI(td) was 0.01 (0.41) litre min(-1) m(-2) (r(2)=0.11, P=0.04). The concordance rates between changes in CI(pw) and CI(td) induced by volume expansion and norepinephrine were 73% and 60%, respectively. The bias between changes in CI(pw) and CI(td) significantly correlated with changes in total systemic vascular resistance (r(2)=0.41, P<0.0001). CONCLUSIONS: The third-generation FloTrac/Vigileo device was moderately reliable for tracking changes in CI induced by volume expansion and poorly reliable for tracking changes in CI induced by norepinephrine.

Erythropoietin ameliorates damage to the placenta and fetal liver induced by exposure to lipopolysaccharide.

Intrauterine infection and inflammation have been causally linked to preterm birth and fetal brain injury. Using an ovine model of endotoxin-induced brain injury we have recently shown that recombinant human erythropoietin (rhEPO) reduces brain injury and protects against damage to myelination in major myelinated axon tracts. Our present objective was to determine whether rhEPO is also protective of the placenta and the fetal liver, organs which could influence fetal well-being. At 107 +/- 1 days of gestational age (DGA) chronically catheterized fetal sheep were randomly assigned to receive, on 3 consecutive days, either: 1) an i.v. bolus dose of lipopolysaccharide (LPS; approximately 0.9 microg/kg; n = 8); 2) i.v. bolus dose of LPS, followed at 1 h by 5000 IU/kg of rhEPO (LPS + rhEPO, n = 8); 3) rhEPO (n = 3). Seven untreated fetuses served as controls (n = 7). The placenta and fetal liver were examined histologically at 116 +/- 1 DGA; a placental injury index was formulated comprising measures of placental area, apoptosis, tissue injury and the size of the intervillous space. In LPS-exposed fetuses this index was greater than in control or rhEPO alone fetuses (p < 0.02). Treatment of LPS-exposed fetuses with rhEPO resulted in a reduction in the index (p < 0.05) and in the extent of liver necrosis. We conclude that rhEPO offers protection to the placenta and fetal liver in the presence of acute inflammation.

Genetic alteration of the D2 domain abolishes von Willebrand factor multimerization and trafficking into storage.

BACKGROUND: The large von Willebrand factor (VWF) propeptide (VWFpp) plays a critical role in the multimerization and regulated storage of the mature VWF protein. Although our laboratory and others have identified mutations in von Willebrand disease patients that disrupt VWF multimerization, little is known about the affect of mutations on the regulated storage of VWF. PATIENTS/METHODS: We identified a heterozygous 18 base pair, in-frame deletion in exon 12 of the VWF gene in a patient with an unusual, dimer-intense multimer pattern. This deletion results in loss of amino acids 436-442 of VWFpp, which include one cysteine. RESULTS: Through expression studies, we demonstrate reduced secretion, loss of VWF multimerization, and defective regulated storage of the variant VWF. The loss of VWF storage is secondary to loss of propeptide storage resulting from an apparently defective sorting signal on VWFpp. Suprisingly, coexpressed wild-type VWF or VWFpp functioned in trans to partially restore multimerization of VWF from the variant allele. CONCLUSIONS: The deletion of six amino acids in VWFpp results in defects in VWF processing, regulated storage, and function. Although VWFpp may usually function in a homotypic fashion, acting on its own mature VWF subunit, VWFpp may retain the ability to function in trans on VWF expressed from the variant allele.

[Evaluation of treatment outcome in congenital clubfoot by subtalar release]. / Ocena wyników leczenia wrodzonej stopy konsko-szpotawej metoda uwolnienia podskokowego.

This paper presents an analysis of the results of congenital clubfoot treatment by partial or complete subtalar release performed through the Cincinnati approach. Of 116 patients (142 feet) who underwent surgery in the years 1995-1996, 33 (47 feet) came in for final follow-up. The type of primary deformity was defined in only in 36 feet. There were 25 type II deformity and 1 type III deformity. Total subtalar release was performed in 39 feet. Partial subtalar release was performed in 8 feet. During the release procedure, the calcaneo-cuboid joint was not opened, but stabilized with a K-wire. Clinical results were assessed according to the Magone classification. Radiological results were assessed according to the modified criteria of Scientific Committee of the XXI Meeting of the Polish Orthopedic Society held in 1976. Talo-navicular reposition was assessed according to Napiontek. Follow-up time ranged from 40 to 54 months (mean: 48 months). The clinical assessment revealed that the analyzed group as a whole gave 82.2 points (yielding a good result). Very good results were noted in 12 feet (25%), good results in 21 (45%), satisfactory results in 7 (15%) and poor results in 7 (15%). Analysis of radiological results yielded on average 2.5 points (0-7 points). Good results were noted in 45 feet (96%) and satisfactory in 2 feet. A talo-calcaneal index of less than 55 degrees was noted in 23 feet.

Cerebral palsy: progress in diagnosis and management.

The purpose of this article was to present the etiologic factors involved in the nonprogressive, early brain damage that leads to cerebral palsy. Progress in the diagnostics and management of postural and motor function disabilities are described. A major contribution to this progress was made by improved understanding of the neurophysiological basis of motor development and developmental diagnosis in pediatric practice.