Preventative strategies for low anterior resection syndrome.

BACKGROUND: A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly understood and challenging to treat. Despite this, prevention strategies are commonly overlooked. Our aim was to review the pathophysiology of LARS and explore current evidence on the efficacy and feasibility of prophylactic techniques. METHODS: A literature review was performed between [1st January 2000 to 1st October 2023] for studies which investigated preventative interventions for LARS. Mechanisms by which LARS develop are described, followed by a review of prophylactic strategies to prevent LARS. Medline, Cochrane, and PubMed databases were searched, 189 articles screened, 8 duplicates removed and 18 studies reviewed. RESULTS: Colonic dysmotility, anal sphincter dysfunction and neorectal dysfunction all contribute to the development of LARS, with the complex mechanism of defecation interrupted by surgery. Transanal irrigation (TAI) and pelvic floor rehabilitation (PFR) have shown benefits in preventing LARS, but may be limited by patient compliance. Intraoperative nerve monitoring (IONM) and robotic-assisted surgery have shown some promise in surgically preventing LARS. Nerve stimulation and other novel strategies currently used in treatment of LARS have yet to be investigated in their roles prophylactically. CONCLUSIONS: To date, there is a limited evidence base for all preventative strategies including IONM, RAS, PFP and TAI. These strategies are limited by either access (IONM, RAS and PFP) or acceptability (PFP and TAI), which are both key to the success of any intervention. The results of ongoing trials will serve to assess acceptability, while technological advancement may improve access to some of the aforementioned strategies.

Rapid Cycle Deliberate Practice Versus Traditional Simulation for Training Extracorporeal Membrane Oxygenation Specialists in Circuit Air Emergency Management: A Randomized Trial.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a highly complex therapy used to support critically ill patients. Simulation-based training of ECMO specialists in the management of ECMO emergencies has been described in the literature, but optimal methods are not currently established. The objective of this study was to compare rapid cycle deliberate practice (RCDP) simulation versus traditional simulation (TS) with reflective debriefing for training ECMO specialists in the management of arterial air emergencies. METHODS: A prospective, randomized, pre-post interventional design was used to compare the impact of RCDP training with that of TS training on ECMO specialist performance during a simulated ECMO circuit emergency. Participants were divided into 2 training groups-RCDP and TS. Each participant completed a simulated arterial air emergency scenario before training, immediately after training, and again 3 months later. The primary outcome was the time required by individual participants to complete critical clinical actions. RESULTS: Twenty-four ECMO specialists completed the study. Immediately after the training, the RCDP group had faster times to dissociate the patient from the ECMO circuit (11-seconds RCDP vs. 16-seconds TS, P = 0.03) and times to re-establish ECMO support (59-seconds RCDP vs. 82.5-seconds TS, P = 0.01). Follow-up testing at 3 months showed persistence in faster times to re-establish ECMO support in the RCDP group (114-seconds RCDP vs. 199-seconds TS, P = 0.01). CONCLUSIONS: Rapid cycle deliberate practice simulation provides a superior curriculum and method of training ECMO specialists in the management of arterial air emergencies in comparison with traditional simulation.

Ropivacaine and Ketorolac Wound Infusion for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of wound infusion with ropivacaine plus ketorolac compared with placebo for post-cesarean delivery analgesia in women who received a multimodal analgesic regimen including intrathecal morphine. METHODS: In a randomized double-blind study, women undergoing scheduled cesarean delivery under spinal or combined spinal epidural anesthesia were randomized to wound infusion with ropivacaine 0.2% plus ketorolac, or saline placebo using an elastometric pump for 48 hours. The primary outcome was pain score with movement at 24 hours after surgery (0-10 scale, 0=no pain and 10=worst possible pain). Secondary outcomes included pain scores at rest at 24 hours, pain scores at rest and with movement at 2 and 48 hours, opioid consumption, and time to first rescue analgesic. A sample size of 35 per group (n=70) was planned. RESULTS: From November 8, 2016, to May 17, 2019, 247 women were screened, and 71 completed the study per protocol: 38 in the placebo group and 33 in the ropivacaine plus ketorolac group. Patient demographics and intraoperative characteristics were comparable between the groups. There was no significant difference between the groups in the primary outcome of pain score with movement at 24 hours (difference in median score 0, 95% CI -1 to 2, P=.94). There were also no significant differences between the placebo and ropivacaine plus ketorolac groups in pain scores at other time points, in total opioid consumption (difference in median consumption -12.5 mg, 95% CI -30 to 5, P=.11), or in time to rescue analgesics (median [interquartile range] 660 [9-1,496] vs 954 [244-1,710] minutes, hazard ratio 0.69, 95% CI 0.41 to 1.17, P=.16). CONCLUSION: There was no benefit of wound infusion with ropivacaine and ketorolac in women who received intrathecal morphine and a multimodal analgesic regimen. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02829944. FUNDING SOURCE: The study was supported in part by Avanos Medical Inc.

Development of Validated Checklists to Evaluate Clinical Specialists in Pediatric ECMO Emergencies Using Delphi Method.

Extracorporeal membrane oxygenation (ECMO) is a low-volume, high-risk modality of care. Clinical specialists (CS) who manage ECMO circuit emergencies vary in background and approach to circuit emergencies based on institutional training standards, leading to variation that may impact the quality of care. Validated checklists to assess CS performance are crucial to eliminate disparities and improve efficiency. This study focused on the development and validation of checklists to evaluate the clinical performance of ECMO CS in three ECMO circuit emergencies. A research team with diverse clinical background from our institution developed the first iteration of three ECMO emergency checklists: (1) venous air, (2) arterial air, and (3) oxygenator failure. A modified Delphi technique with a panel of 11 national content experts in ECMO was used to develop content validity evidence. Rating scales from 1 to 7 were used to evaluate each checklist item. The response rate for three rounds of Delphi was 100%. Items with mean score >4 were kept, and new item recommendations were added based on comments from the panel. The venous air, arterial air, and oxygenator failure checklists were revised from 10, 13, and 9 items to 12, 12, and 10 items, respectively. A Cronbach's α of 0.74 during the second round of responses indicated an acceptable degree of agreement. This study demonstrated content validation of three ECMO emergency checklists to assess performance of ECMO CS using a consensus-based Delphi technique. Future validity evidence should be acquired by implementing these checklists in the simulation environments.

Comparison of Programmed Intermittent Epidural Boluses With Continuous Epidural Infusion for the Maintenance of Labor Analgesia: A Randomized, Controlled, Double-Blind Study.

BACKGROUND: Programmed intermittent epidural boluses may improve the spread of local anesthetics compared to continuous epidural infusion, improving labor analgesia and obstetric outcomes. However, there are limited data from studies using commercially available pumps capable of coadministering programmed intermittent epidural boluses or continuous epidural infusion with patient-controlled epidural analgesia. Therefore, we performed this prospective, randomized, double-blind study to compare the impact of programmed intermittent epidural boluses versus continuous epidural infusion on labor analgesia and maternal/neonatal outcomes. We hypothesized that programmed intermittent epidural boluses will result in lower patient-controlled epidural analgesia consumption compared to that with continuous epidural infusion. METHODS: Following standardized initiation of epidural labor analgesia, women were randomized to receive 0.1% ropivacaine with 2 µg/mL fentanyl as 6-mL programmed intermittent epidural boluses every 45 minutes or continuous epidural infusion at 8 mL/h in a double-blind fashion with similar patient-controlled epidural analgesia settings in both groups. The primary outcome was patient-controlled epidural analgesia consumption per hour. Secondary outcomes included a need for physician interventions, patterns of patient-controlled epidural analgesia use, motor blockade, number of patients who developed hypotension, pain scores, duration of second stage of labor, mode of delivery, and maternal satisfaction. RESULTS: We included 120 patients (61 in programmed intermittent epidural boluses group and 59 in continuous epidural infusion group) in the analysis. The median (interquartile range) patient-controlled epidural analgesia volume consumed per hour was not significantly different between the groups: 4.5 mL/h (3.0-8.6 mL/h) for the continuous epidural infusion group and 4.0 mL/h (2.2-7.1 mL/h) for the programmed intermittent epidural boluses group (P = .17). The Hodges-Lehmann location shift estimate of the difference (95% CI) from the continuous epidural infusion to the programmed intermittent epidural boluses group is 0.9 mL/h (-0.4 to 2.2 mL/h). There were also no significant differences between the groups in any of the secondary outcomes except for higher median (interquartile range) patient-controlled epidural analgesia attempts per given ratio per hour in the programmed intermittent epidural bolus group (0.17 [0.10-0.30] vs 0.12 [0.08-0.18]; P = .03) and more motor block in the continuous epidural infusion group (those with Bromage score <5, 27.5% vs 50.0%; P = .03). CONCLUSIONS: Under the conditions of our study, we did not find improved outcomes with programmed intermittent epidural boluses compared to continuous epidural infusion except for less motor block with programmed intermittent epidural boluses. Future studies should assess whether smaller but clinically important differences exist and evaluate different parameters of programmed intermittent epidural boluses to optimize analgesia and outcomes with this mode of analgesia.

Predicting Severity of Acute Pain After Cesarean Delivery: A Narrative Review.

Cesarean delivery is one of the most common surgical procedures in the United States, with over 1.3 million performed annually. One-fifth of women who undergo cesarean delivery will experience severe pain in the acute postoperative period, increasing their risk of developing chronic pain and postpartum depression, and negatively impacting breastfeeding and newborn care. A growing body of research has investigated tools to predict which patients will experience more severe pain and have increased analgesic consumption after cesarean delivery. These include quantitative sensory testing, assessment of wound hyperalgesia, response to local anesthetic infiltration, and preoperative psychometric evaluations such as validated psychological questionnaires and simple screening tools. For this review, we searched MEDLINE, the Cochrane database, and Google Scholar to identify articles that evaluated the utility of various tools to predict severe pain and/or opioid consumption in the first 48 hours after cesarean delivery. Thirteen articles were included in the final review: 5 utilizing quantitative sensory testing, including patient responses to pressure, electrical, and thermal stimuli; 1 utilizing hyperalgesia testing; 1 using response to local anesthetic wound infiltration; 4 utilizing preoperative psychometric evaluations including the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and simple questionnaires; and 2 utilizing a combination of quantitative sensory tests and psychometric evaluations. A number of modalities demonstrated statistically significant correlations with pain outcomes after cesarean delivery, but most correlations were weak to modest, and many modalities might not be clinically feasible. Response to local anesthetic infiltration and a tool using 3 simple questions enquiring about anxiety and anticipated pain and analgesic needs show potential for clinical use, but further studies are needed to evaluate the utility of these predictive tests in clinical practice.

Cockroach allergen exposure and plasma cytokines among children in a tropical environment.

BACKGROUND: Little is known about the effects of socioeconomic status or cockroach allergen on immune responses in school-age children, particularly in tropical environments. OBJECTIVE: To examine whether cockroach allergen and/or socioeconomic status is associated with plasma cytokine levels in Puerto Rican children. METHODS: This was a cross-sectional study of 532 children (6-14 years old) with (n = 272) and without (n = 260) asthma in San Juan (Puerto Rico). House dust allergens (cockroach [Bla g 2], dust mite [Der p 1], cat dander [Fel d 1], dog dander [Can f 1], and mouse urinary protein [Mus m 1]) were quantified using monoclonal antibody arrays. A panel of 14 cytokines (interleukin [IL]-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon-γ, and tumor necrosis factor-α) was measured in plasma samples. Low household income was defined as less than $15,000 per year (below the median income for Puerto Rico in 2008-2009). Linear regression was used for the analysis of cockroach allergen and plasma cytokines. RESULTS: In a multivariable analysis adjusting for low income and other allergen levels, cockroach allergen was significantly associated with decreased IL-17A and with increased levels of 8 cytokines (IL-4, IL-10, IL-17F, IL-21, IL-25, IL-31, interferon-γ, and tumor necrosis factor-α). After stratifying this analysis by cockroach allergy (ie, having a cockroach positive immunoglobulin E reaction), our findings remained largely unchanged for children sensitized to cockroach but became weaker and statistically nonsignificant for non-sensitized children. CONCLUSION: Cockroach allergen has broad effects on adaptive immune responses in school-age children in a tropical environment, particularly in those sensitized to cockroach.

Maternal depressive symptoms, maternal asthma, and asthma in school-aged children.

BACKGROUND: Little is known about the joint effects of maternal asthma and maternal depression on childhood asthma. OBJECTIVE: To examine whether maternal depression and maternal asthma lead to greater risk of childhood asthma than maternal asthma alone. METHODS: Cross-sectional studies of children (6-14 years old) in San Juan, Puerto Rico (n = 655) and Sweden (n = 6,887) were conducted. In Puerto Rico, maternal depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire. In Sweden, maternal physician-diagnosed depression was derived from national registries, and maternal depressive symptoms were defined using an abbreviated CES-D questionnaire. Childhood asthma was defined as physician-diagnosed asthma plus current wheeze (in Puerto Rico) or plus medication use (in Sweden). Logistic regression was used for multivariable analysis. RESULTS: Compared with Puerto Rican children whose mothers had neither asthma nor depressive symptoms, those whose mothers had asthma but no depressive symptoms had 3.2 times increased odds of asthma (95% confidence interval [CI] = 2.1-4.8) and those whose mothers had asthma and depressive symptoms had 6.5 times increased odds of asthma (95% CI = 3.3-13.0). Similar results were obtained for maternal depression and maternal asthma in the Swedish cohort (odds ratio for maternal asthma without maternal depression = 2.8, 95% CI = 2.1-3.7; odds ratio for maternal asthma and maternal depression = 4.0, 95% CI = 1.7-9.6). Although the estimated effect of maternal asthma on childhood asthma was increased when maternal depressive symptoms (Puerto Rico) or maternal depression (Sweden) was present, there were no statistically significant additive interactions. CONCLUSION: Maternal depression can further increase the risk of asthma in children whose mothers have a history of asthma.

Additional sex combs-like 1 belongs to the enhancer of trithorax and polycomb group and genetically interacts with Cbx2 in mice.

The Additional sex combs (Asx) gene of Drosophila behaves genetically as an enhancer of trithorax and polycomb (ETP) in displaying bidirectional homeotic phenotypes, suggesting that is required for maintenance of both activation and silencing of Hox genes. There are three murine homologs of Asx called Additional sex combs-like1, 2, and 3. Asxl1 is required for normal adult hematopoiesis; however, its embryonic function is unknown. We used a targeted mouse mutant line Asxl1(tm1Bc) to determine if Asxl1 is required to silence and activate Hox genes in mice during axial patterning. The mutant embryos exhibit simultaneous anterior and posterior transformations of the axial skeleton, consistent with a role for Asxl1 in activation and silencing of Hox genes. Transformations of the axial skeleton are enhanced in compound mutant embryos for the polycomb group gene M33/Cbx2. Hoxa4, Hoxa7, and Hoxc8 are derepressed in Asxl1(tm1Bc) mutants in the antero-posterior axis, but Hoxc8 expression is reduced in the brain of mutants, consistent with Asxl1 being required both for activation and repression of Hox genes. We discuss the genetic and molecular definition of ETPs, and suggest that the function of Asxl1 depends on its cellular context.

Population Structure, Chemotype Diversity, and Potential Chemotype Shifting of Fusarium graminearum in Wheat Fields of Manitoba.

This study was to investigate the variation of acetyl ester derivative of DON at 15-position oxygen (15ADON) and acetyl ester derivative of DON at 3-position oxygen (3ADON) chemotypes and potential chemotype shifting of Fusarium graminearum based on the population structure of this species in Manitoba. The study was conducted in 15 locations with wheat cvs. Superb and AC Barrie in Manitoba from 2004 to 2005. Percentages of chemotypes 3ADON and 15ADON of F. graminearum ranged from 0 to 95.7 and 4.3 to 100%, respectively. The 3ADON chemotype was distributed in the southern part of Manitoba and predominant in Morris and Horndean. The two chemotypes almost shared the same percentage in Portage la Prairie. The 15ADON chemotype was predominant in the other locations. Significant gene flow was found among the populations from Sanford, Portage la Prairie, Hamiota, Plumas, Rapid City, and Virden; the populations from Cartier, Rivers, Killarney, and Souris; and the populations from Morris, Kenville, and Dauphin. There were no differences between the populations from two wheat cultivars and two chemotypes. The great variation of chemotype likely resulted from the great genetic diversity of F. graminearum. Sexual recombination, population age, and cropping system could result in genetic and chemotypic diversities. Wheat seed shipment and long-distance spore transportation of F. graminearum potentially caused the genetic migration and chemotype shifting in Manitoba.

Initial and mid-term results of a 4F compatible self-expanding low strut profile nitinol stent in the superficial femoral artery.

PURPOSE: To evaluate the initial and mid-term results of a new self-expanding low strut profile nitinol stent for treatment of atherosclerotic lesions stenoses and occlusions in the superficial femoral artery (SFA). MATERIALS AND METHODS: In 8 patients (4 male, 4 female, mean age 74.8 +/- 8.8 years) with SFA lesions and non-satisfying results after PTA treatment alone, 10 self-expanding nitinol Xpert stents were deployed via a 4 F sheath. Stent characteristics and handling were graded by the interventionalist. Fontaine classification, duplex flow measurements and ankle brachial index (ABI) at rest and stress were taken prior and one day after stent placement. Patients were followed 3, 6 and 12 months after the procedure obtaining the same parameters at each appointment. RESULTS: Initial stent treatment was successful in all patients. Stent handling and positioning were rated very good and safe. All patients improved clinically by at least one Fontaine stage (range before treatment: stage IIb to IV). The mean ABI at rest (stress) improved initially from 0.68 (0.70) to 1.07 (0.99). During a mean follow-up period of 8.3 months no case of clinically relevant in-stent stenosis was observed with stable values of ABI at rest and stress. CONCLUSION: Treatment of SFA lesions using the 4F-compatible self-expanding nitinol Xpert stent is technically simple, safe and shows good initial and mid-term results.

Heart rate at lactate threshold and cycling time trials.

The purpose of this investigation was to relate the heart rate and lactate response during simulated cycling time trials to incremental laboratory tests. Subjects (N = 10) were tested for .V(O2)max (56.1 +/- 2.4 ml.kg(-1).min(-1) ) and lactate threshold during incremental tests to exhaustion. Power output and heart rate (HR) at threshold was assessed by 3 methods: lactate deflection point (LaT), onset of blood lactate accumulation (OBLA), and the point on the lactate curve at maximal distance from a line connecting starting and finishing power output (Dmax). Power output determined at these thresholds was 282.1 +/-4.2, 302.5 +/-1.3, and 296.0 +/- 1.8 W, respectively, whereas HR was determined to be 88.6 +/- 0.01, 92.2 +/- 0.01, and 91.0 +/- 0.01% of maximum, respectively. Power output and HR were significantly lower for LaT than for the other 2 methods (p < 0.05). On separate visits, cyclists were instructed to perform maximum efforts for 30 and 60 minutes (30TT and 60TT). Lactate, HR, perceived exertion (RPE), and metabolic variables were measured during the time trials. During the 30TT, participants sustained a significantly higher lactate level (5.29 +/- 0.3 vs. 3.43 +/- 0.3 mmol.L(-1), p < 0.001), percentage of maximum HR (%HRmax) (90.3 +/- 0.02 vs. 84.6 +/- 0.01, p = 0.009), and overall RPE (15.5 +/- 0.5 vs. 14.4 +/- 0.5, p = 0.009), than during the 60TT. .V(O2) was not significantly different between the time trials; however, .V(CO2) (p = 0.008), ventilation (p = 0.004), and respiratory exchange ratio (p = 0.02) were significantly higher during the 30TT. Correlations were found between HR at LaT (r = 0.78), OBLA (r = 0.78), and Dmax (r = 0.71) for the 60TT, but not for the 30TT. These data suggest that despite a large variability in blood lactate during time trial efforts of 30 and 60 minutes (from 1.8 to 10.8 mmol.L(-1)), HR was consistently 90% of maximum for the 30TT and 85% for the 60TT. HR during the 30TT was approximated by HR corresponding to OBLA and Dmax, whereas HR during 60TT was approximated by LaT.

Mutational analysis of the N-terminus in Schistocerca gregaria ion-transport peptide expressed in Drosophila Kc1 cells.

The functions of the 6-7 amino acid N-terminal domain conserved in insect and crustacean members of the hyperglycemic hormone (CHH) family were assayed by site-directed mutagenesis of Schistocerca gregaria ion-transport peptide (SchgrITP). Mutant peptides were expressed in Drosophila Kc1 cells and tested in a biological assay measuring stimulation of active Cl(-) transport across the locust ileum. We exchanged the N-terminal domain of SchgrITP with that of the shrimp Penaeus japonicus hyperglycemic hormone leaving the remainder of SchgrITP intact. The chimeric peptide was completely inactive in the ileal bioassay, showing that the N-terminus of SchgrITP is essential and that the 2 amino acids (phenylalanine-3 and aspartate-4) conserved in the shrimp and locust peptides are not sufficient for function. We made all possible alanine substitutions in the SchgrITP N-terminal domain. Only phenylalanines 2 and 3 were essential for function in the locust ileal bioassay. All N-terminal mutations were cleaved correctly from the prepropeptide, and expressed in similar concentrations as wild-type ITP suggesting the specific amino acids are not essential for these functions. Post-translational modification may explain a minor ITP isomorph observed in Drosophila Kc1 cell expression. Alanine substitution at position 2 produced a weak ITP antagonist. These structure-function studies, the first for any member of the CHH family, show that both conserved and unconserved amino acids contribute to SchgrITP ion-transport function and that the conserved aspartate in position 4 is required for a yet uncharacterized function.

Lung function and nutritional status of semi-nomadic Fulani children and adolescents in northern Nigeria.

The Fulani are semi-nomadic pastoralists of the western Sahel whose culture and economy are centered on cattle. We have shown previously that Fulani children and adolescents (5-18 years old) are stunted and underweight. Nutritional status and lung function were studied in Fulani children and adolescents (n = 70), aged 6-18, and compared with a non-Fulani, rural Nigerian control group (n = 153) of the same age. Participants were restricted to healthy individuals with no prior history of respiratory disease and no symptoms of an upper respiratory tract infection within the past 6 weeks. Significant deficits in forced vital capacity (FVC; Fulani males, 1.51 l; non-Fulani males, 1.86 l, p = 0.009; Fulani females, 1.36 l; non-Fulani females, 1.79 l, p < 0.001), forced expiratory volume in one second (FEV1; Fulani males, 1.44 l; non-Fulani males, 1.76 l, p = 0.02; Fulani females, 1.24 l; non-Fulani females, 1.69 l, p < 0.001), and peak expiratory flow rate (PEFR; Fulani males, 2.69 l/s; non-Fulani males, 3.48 l/s, p = 0.002; Fulani females, 2.29 l/s; non-Fulani females, 3.35 l/s, p < 0.001) were found in both the Fulani boys and girls compared with the non-Fulani controls. The diminished lung function in the Fulani group could be attributed to respiratory muscle weakness or an overall deficit in energy.

Monitoring intravascular volumes for postoperative volume therapy.

BACKGROUND AND OBJECTIVE: The feasibility of monitoring measured intravascular volumes and the cardiac filling pressures were compared to reflect the optimal volume status of postoperative patients. METHODS: In a prospective clinical study, 14 hypovolaemic adult patients were included after cardiac surgery. All patients received 1,000 mL hydroxyethyl starch after meeting the authors' criteria for hypovolaemia. Pressures were measured by use of a pulmonary artery catheter and volumes were determined by double-indicator dilution technique. RESULTS: Stroke volume index (SVI), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), intrathoracic blood volume index (ITBVI) and total circulating blood volume (TBVIcirc) increased significantlyaftervolumeloading(30.7 +/- 9.8 to 41.7 +/- 9.6 mLm(-2), 4.9 +/- 1.7 to 9.1 +/- 2.3mmHg, 6.6 +/- 1.3 to 10.6 +/- 1.9 mmHg, 858 +/- 255 to 965 +/- 163 mLm(-2), and 1,806 +/- 502 to 2,110 +/- 537 mLm(-2), respectively). During the subsequent 1 h steady-state period, CVP and PAOP decreased significantly (9.1 +/- 2.2 to 7.4 +/- 2.2 mmHg and 10.6 +/- 1.9 to 9.2 +/- 2.0 mmHg, respectively), whereas SVI and intravascular volumes remained unchanged. The changes of CVP and PAOP did not correlate with changes in stroke volume during volume loading (r2 = 0.06 and 0.03, respectively) and during steady-state (r2 = 0.17 and 0.00 respectively). On the other hand, a significant correlation was found between changes of the intrathoracic blood volume and changes in stroke volume during the volume loading (r2 = 0.67) and also during the steady-state phase (r2 = 0.83). CONCLUSIONS: Intrathoracic blood volume reflects more accurately the preload dependency of cardiac output in postoperative patients than left/right-sided cardiac filling pressures.

Life threatening cardiopulmonary failure in an infant following protamine reversal of heparin after cardiopulmonary bypass.

Life threatening cardiopulmonary failure following protamine reversal of heparin after cardiopulmonary bypass (CPB) was reported to occur in adults but rarely in children. Atrial septal defect closure was performed in a 6-week-old infant erroneously suspected to suffer from right atrial thrombosis in addition. Protamine administration after CPB led to critical pulmonary hypertension and severe haemorrhagic pulmonary oedema resulting in severe hypoxia. Inhaled nitric oxide, together with high frequency oscillation ventilation supplemented by intravenous prostacycline, enabled complete recovery of cardiopulmonary and neurological function. Life threatening cardiovascular compromise after intravenous protamine can occur even in young infants which then require challenging paediatric critical care.

Site-specific recognition of a 70-base-pair element containing d(GA)(n) repeats mediates bithoraxoid polycomb group response element-dependent silencing.

Polycomb group proteins act through Polycomb group response elements (PREs) to maintain silencing at homeotic loci. The minimal 1.5-kb bithoraxoid (bxd) PRE contains a region required for pairing-sensitive repression and flanking regions required for maintenance of embryonic silencing. Little is known about the identity of specific sequences necessary for function of the flanking regions. Using gel mobility shift analysis, we identify DNA binding activities that interact specifically with a multipartite 70-bp fragment (MHS-70) downstream of the pairing-sensitive sequence. Deletion of MHS-70 in the context of a 5.1-kb bxd Polycomb group response element derepresses maintenance of silencing in embryos. A partially purified binding activity requires multiple, nonoverlapping d(GA)(3) repeats for MHS-70 binding in vitro. Mutation of d(GA)(3) repeats within MHS-70 in the context of the 5.1-kb bxd PRE destabilizes maintenance of silencing in a subset of cells in vivo but gives weaker derepression than deletion of MHS-70. These results suggest that d(GA)(3) repeats are important for silencing but that other sequences within MHS-70 also contribute to silencing. Antibody supershift assays and Western analyses show that distinct isoforms of Polyhomeotic and two proteins that recognize d(GA)(3) repeats, the TRL/GAGA factor and Pipsqueak (Psq), are present in the MHS-70 binding activity. Mutations in Trl and psq enhance homeotic phenotypes of ph, indicating that TRL/GAGA factor and Psq are enhancers of Polycomb which have sequence-specific DNA binding activity. These studies demonstrate that site-specific recognition of the bxd PRE by d(GA)(n) repeat binding activities mediates PcG-dependent silencing.