Fatal intrahepatic hemorrhage after nadroparin use for total hip arthroplasty.

Low-molecular-weight heparins have become the predominant choice for deep venous thrombosis prophylaxis and treatment. However, their use may cause bleeding complications. Intrahepatic bleeding is exceptional and only very few cases have been described. The authors present a unique case of fatal intrahepatic hematoma complicating nadroparin use in a 65-year-old woman with a hepatic cyst who was admitted to hospital for unilateral total hip arthroplasty. At autopsy, hemoperitoneum (2,000 ml of blood and clots) was evident. A ruptured sub-capsular hematoma involving the right lobe of the liver was observed. The hemorrhage within the cyst induced by the nadroparin use was likely responsible for the subsequent hepatic hematoma, liver rupture, and death. This case highlights the need for pathologists and surgeons to be aware of the possibility of intrahepatic hematoma in patients who have received low-molecular-weight heparins, undergone major surgery and present postoperative hemodynamic instability, especially in those with preoperative diagnosis of hepatic cyst.

Nuclear localization of mouse fibroblast growth factor 2 requires N-terminal and C-terminal sequences.

In vertebrates, different isoforms of fibroblast growth factor 2 (FGF2) exist, which differ by their N-terminal extension. They show different localization and expression levels and exert distinct biological effects. Nevertheless, genetic inactivation of all FGF2 isoforms in the mouse results in only mild phenotypes. Here, we analyzed mouse FGF2, and show that, as in the human, mouse FGF2 contains CTG-initiated high molecular-weight (HMW) isoforms, which contain a nuclear localization signal, and which mediate localization of this isoform to the nucleus. Using green fluorescent protein-FGF2 fusions, we furthermore observed, that C-terminal deletions disable nuclear localization of the short low-molecular-weight (LMW) 18-kDa isoform. This loss of specific localization is accompanied by a loss in heparin binding. We therefore suggest that, first, localization of mouse FGF2 is comparable to that in other vertebrates and, second, FGF2 contains at least two sequences important for nuclear localization, a nuclear localization sequence at the N terminus which is only contained in the HMW isoform, and another sequence at the C terminus, which is only required for localization of the LMW 18-kDa isoform.

Signal transduction in plant-beneficial rhizobacteria with biocontrol properties.

Biological control of root pathogens--mostly fungi--can be achieved by the introduction of selected bacterial inoculants acting as 'biopesticides'. Successful inoculants have been identified among Gram-negative and Gram-positive bacteria, often belonging to Pseudomonas spp. and Bacillus spp., respectively. Biocontrol activity of a model rhizobacterium, P. fluorescens CHAO, depends to a considerable extent on the synthesis of extracellular antimicrobial secondary metabolites and exoenzymes, thought to antagonize the pathogenicity of a variety of phytopathogenic fungi. The regulation of exoproduct formation in P. fluorescens (as well as in other bacteria) depends essentially on the GacS/GacA two-component system, which activates a largely unknown signal transduction pathway. However, recent evidence indicates that GacS/GacA control has a major impact on target gene expression at a post-transcriptional level, involving an mRNA target sequence (typically near the ribosome binding site), two RNA binding proteins (designated RsmA and RsmE), and a regulatory RNA (RsmZ) capable of binding RsmA. The expression and activity of the regulatory system is stimulated by at least one low-molecular-weight signal. The timing and specificity of this switch from primary to secondary metabolism are essential for effective biocontrol.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Outcomes in neurosurgical patients who develop venous thromboembolism: a review of the RIETE registry.

OBJECTIVES: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes. METHODS: Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery. RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058). CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation.

Migration of dissolved organic carbon in biochars and biochar-mineral complexes

The objective of this work was to determine the contribution of dissolved organic carbon (DOC) from a biochar mineral complex (BMC), so as to better understand the interactions between DOC, biochar, clay, and minerals during thermal treatment, and the effects of BMC on amended soils. The BMC was prepared by heating a mixture of a H3PO4-treated saligna biochar from Acacia saligna, clays, other minerals, and chicken manure. The BMC was applied to a sandy loam soil in Western Australia, where wheat was grown. Liquid chromatography-organic carbon detection (LC-OCD) tests were carried out on water extracts from the untreated biochar, the BMC, the BMC-amended soil, and on a control soil to measure the DOC concentration. LC-OCD tests provide a fingerprint of the DOC, which allows the fractions of DOC to be determined. Thermal processing enhanced the reaction of the A. saligna biochar with manure, clays and minerals, and affected the distribution of the DOC fractions. Notably, the process leads to immobilization of hydrophobic DOC and to an increase in the concentration of low-molecular-weight neutrals in the BMC. The application of the BMC to soil increases the DOC in the amended soil, especially the biopolymer fraction.

Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.

Hour of birth as a prognostic factor for perinatal death.

The analysis of the 220,540 births and 2152 perinatal deaths recorded in Switzerland between 1979 and 1981 showed a variation of perinatal mortality rates (PMR) according to the hour of birth. The PMR for babies born between 4 pm and 2 am was 12 per 1000, contrasting with a figure of 8.4 per 1000 for babies born between 2 am and 4 pm. This pattern, which was fairly constant throughout the week, was characterised by a slow and steady increase from the very early morning, reaching a maximum in the late evening. There was also an hour-to-hour variation in the proportion of babies born weighing less than 2500 g, with a maximum in the evening and a less pronounced peak in the morning: the mortality rates by birthweight were raised only in the evening. Since the availability of hospital staff and equipment also follows a circadian rhythm, the variation in PMR may be related to a circadian rhythm of quality of care or possibly to chronobiological or selection factors.

Retentiopolymeerin optimointi täyteaineiden yhtäaikaisannostelussa

Kirjallisuusosassa perehdyttiin retentioaineisiin ja täyteaineisiin sekä retentioaineiden ja rainanmuodostusolosuhteiden vaikutukseen retentioon, vedenpoistoon ja paperin ominaisuuksiin. Tarkemmin kirjallisuusosassa keskityttiin täyteaineiden esiflokkaukseen, retentiopolymeerin adsorptioon sekä retentiopolymeerien ja täyteaineiden annostelutapoihin. Kokeellisessa osassa tutkittiin sarjaa retentiopolymeerejä, joiden varaustiheys ja moolimassa muuttuivat. Yksi polymeereistä oli kahdesta polymeeristävalmistettu suoladispersio ja yksi modifioitu kationinen PAM. Näillä polymeereillä käytiin läpi koesarjoja, joissa muutettiin täyteaineen annosteluaikaa retentiopolymeerin annosteluajan pysyessä vakiona. Lähinnä vertailtiin keskenään perinteistä annostelua, jossa täyteaine annosteltiin paljon ennen retentiopolymeeriä,ja yhtäaikaista annostelua, jossa molemmat annosteltiin yhtä aikaa lähellä perälaatikkoa. Kokeet tehtiin MBF-laitteella, jolla pystytään paperikonetta vastaaviin pulsaatiotaajuuksiin ja sillä voidaan valmistaa tasoviirakoneella valmistetunpaperin kaltaisia laboratorioarkkeja. Valmistetuista arkeista tutkittiin retentioita ja paperiteknisiä ominaisuuksia. Laboratoriokokeiden perusteella yhtäaikainen annostelu antoi paremmat täyteaineretentiot verrattaessa perinteiseen annosteluun lähes kaikissa koesarjoissa. Varsinkin lyhytketjuiset polymeerit näyttivättoimivan hyvin yhtäaikaisannostelulla, mikä saattaisi johtua siitä, että lyhyt reagointiaika sulpun kanssa on lyhytketjuisille polymeereille edullinen, sillä silloin polymeeriketjun konformaatio ei ehdi asettua liian alhaiseksi ja ketjun toimintakyky säilyy parempana. Polymeerin varaustiheyden kasvaessa riittävästi laski täyteaineretentio seuraavissa tapauksissa: SC-massa + kaoliini ja SC-massa +GCC kummallakin annostelulla sekä SC-massa + PCC A perinteisellä annostelulla. Hienopaperimassalla samaa trendiä noudatti täyteaine GCC kummallakin annostelulla, kun taas PCC H:ta käytettäessä paranivat täyteaineretentiot molemmilla annosteluilla. Retentiopolymeerin moolimassan kasvaessa riittävästi kääntyi täyteaineretentio laskuun täyteaineilla GCC ja kaoliini, kun käytettiin SC-massaa. Hienopaperimassalla GCC noudatti tätä samaa taipumusta. Sen sijaan SC-massalla PCC A:takäytettäessä täyteaineretentio puolestaan nousi hieman moolimassan kasvaessa. Näin kävi myös hienopaperimassalla, kun täyteaineena käytettiin PCC H:ta. Käytettäessä SC-massaa, perinteisellä annostelulla saatiin parempi tai yhtä hyvä valonsironta kuin yhtäaikaisella annostelulla kaikilla täyteaineilla. Tämä saattaisi johtua siitä, että yhtäaikaisannostelulla on muodostunut suurempia täyteaineflokkeja, mikä on alentanut valoa sirottavia pintoja. Täyteaineista korkeimmat valonsirontakertoimet antoi PCC A ja alhaisimmat kaoliini. PCC A:lla oli kapein partikkelikokojakauma, mikä korottaa paperin valonsirontaa. Hienopaperimassalla valonsirontakerroin ja opasiteetti suurenivat GCC-pitoisuuden kasvaessa kummallakin annostelulla, mikä voisi johtua täyteainepartikkelien antamasta paremmasta sironnasta. Yhtäaikaisella annostelulla saavutettiin huomattavasti paremmat valonsironnan arvot perinteiseen annosteluun verrattuna. PCC H-pitoisuuden kasvaessa suurenivat myös valonsirontakerroin ja opasiteetti kummallakin annostelulla. PCC H antoi korkeammat valonsirontakertoimet kuin GCC. PCC omaa suuremman valonheijastusluvun kuin GCC, minkä vuoksi se antaa paremmat valonsirontakertoimen arvot. PCC H:n partikkelikokojakauma oli myös kapeampi kuin GCC:n, mikä mahdollisti paremman valonsironnan ja opasiteetin saavuttamisen.

Water, energy and early postnatal growth in preterm infants.

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth.

EndoG links Bnip3-induced mitochondrial damage and caspase-independent DNA fragmentation in ischemic cardiomyocytes

Mitochondrial dysfunction, caspase activation and caspase-dependent DNA fragmentation are involved in cell damage in many tissues. However, differentiated cardiomyocytes repress the expression of the canonical apoptotic pathway and their death during ischemia is caspase-independent. The atypical BH3-only protein Bnip3 is involved in the process leading to caspase-independent DNA fragmentation in cardiomyocytes. However, the pathway by which DNA degradation ensues following Bnip3 activation is not resolved. To identify the mechanism involved, we analyzed the interdependence of Bnip3, Nix and EndoG in mitochondrial damage and DNA fragmentation during experimental ischemia in neonatal rat ventricular cardiomyocytes. Our results show that the expression of EndoG and Bnip3 increases in the heart throughout development, while the caspase-dependent machinery is silenced. TUNEL-positive DNA damage, which depends on caspase activity in other cells, is caspase-independent in ischemic cardiomyocytes and ischemia-induced DNA high and low molecular weight fragmentation is blocked by repressing EndoG expression. Ischemia-induced EndoG translocation and DNA degradation are prevented by silencing the expression of Bnip3, but not Nix, or by overexpressing Bcl-xL. These data establish a link between Bnip3 and EndoG-dependent, TUNEL-positive, DNA fragmentation in ischemic cardiomyocytes in the absence of caspases, defining an alternative cell death pathway in postmitotic cells.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

Bivalirudin for patients with acute coronary syndromes

Background: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. Methods: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. Results: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P = 0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P = 0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). Conclusions: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158.)