Comparison of three different methods to confirm tracheal tube placement in emergency intubation

OBJECTIVES: Verification of endotracheal tube placement is of vital importance, since unrecognized esophageal intubation can be rapidly fatal (death, brain damage).The aim of our study was to compare three different methods for immediate confirmation of tube placement: auscultation, capnometry and capnography in emergency conditions in the prehospital setting. DESIGN AND SETTING: Prospective study in the prehospital setting. PATIENTS AND INTERVENTIONS: All adult patients (>18 years) were intubated by an emergency physician in the field. Tube position was initially evaluated by auscultation. Then, capnometry was performed with infrared capnometry and capnography with infrared capnography. The examiners looked for the characteristic CO(2) waveform and value of end-tidal carbon dioxide (EtCO(2)) in millimeters of mercury. Determination of final tube placement was performed by a second direct visualization with laryngoscope. Data are mean +/- SD and percentages. MEASUREMENTS AND RESULTS: Over a 4year period, 345 patients requiring emergency intubation were included. Indications for intubation included cardiac arrest ( n=246; 71%) and non-arrest conditions ( n=99; 29%). In nine (2.7%) patients, esophageal tube placement occurred. The esophageal intubations were followed by successful endotracheal intubations without complications. The capnometry (sensitivity and specificity 100%) and capnography (sensitivity and specificity 100%) were better than auscultation (sensitivity 94% and specificity 83%) in confirming endotracheal tube placement in non-arrest patients ( p<0.05). Capnometry was highly specific (100%) but not sensitive (88%) for correct endotracheal intubation in patients with cardiopulmonary arrest (capnometry versus auscultation and capnometry versus capnography, p<0.05). CONCLUSION: Capnography is the most reliable method to confirm endotracheal tube placement in emergency conditions in the prehospital setting.     

Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours

Epigenetic events play an important role in tumour progression and also contribute to escape of the tumour from immune surveillance. In this study, we investigated the up-regulation of major histocompatibility complex (MHC) class I surface expression on tumour cells by epigenetic mechanisms using a murine tumour cell line expressing human E6 and E7 human papilloma virus 16 (HPV16) oncogenes and deficient in MHC class I expression, as a result of impaired antigen-presenting machinery (APM). Treatment of the cells with the histone deacetylase inhibitor Trichostatin A, either alone or in combination with the DNA demethylating agent 5-azacytidine, induced surface re-expression of MHC class I molecules. Consequently, the treated cells became susceptible to lysis by specific cytotoxic T lymphocytes. Further analysis revealed that epigenetic induction of MHC class I surface expression was associated with the up-regulation of APM genes [transporter associated with antigen processing 1 (TAP-1), TAP-2, low-molecular-mass protein 2 (LMP-2) and LMP-7]. The results demonstrate that expression of the genes involved in APM are modulated by epigenetic mechanisms and suggest that agents modifying DNA methylation and/or histone acetylation have the potential to change the effectiveness of antitumour immune responses and therapeutically may have an impact on immunological output.     

Neurobehavioral continuity from fetus to neonate

Neurobehavior represents development of the central nervous system (CNS). Fetuses and newborns exhibit a large number of endogenously generated motor patterns, among which general movements are often investigated pre- and post-natally. Spontaneous activity is probably a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli while testing reflexes. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects particularly on brain growth and function. Unfavorable intrauterine environment can affect adversely brain growth. All endogenously generated movement patterns from un-stimulated CNS might be observed as early as from the seven to eight weeks' gestation, with a rich repertoire of movements within the next two or three weeks, continuing for five to six months postnatally. It is still uncertain whether a new scoring system for prenatal neurological assessment will be adequate for the distinction between normal and abnormal fetuses in low-risk pregnancies. The continuity of behavioral patterns from prenatal to postnatal life might answer these intriguing questions.     

Mutation Screening of the HGD Gene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2‐dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU‐causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.     

Heterogeneity in Rhesus Macaque Complement Factor H Binding to Meningococcal Factor H Binding Protein (FHbp) Informs Selection of Primates To Assess Immunogenicity of FHbp-Based Vaccines

Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines.     

Geometric cues for directing the differentiation of mesenchymal stem cells

Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.     

Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, ther...     

Comparison of two nutritional assessment methods in gastroenterology patients

AIM:To investigate and compare efficacy and differences in the nutritional status evaluation of gastroenterology patients by application of two methods:subjective global assessment(SGA) and nutritional risk index(NRI).METHODS:The investigation was performed on 299 hospitalized patients,aged 18-84 years(average life span 55.57 &#177; 12.84),with different gastrointe-stinal pathology,admitted to the Department of Gastroenterohepatology,Clinical and Hospital Center “Bezanijska Kosa“ during a period of 180 d.All the...     

Frequency of selected thrombophilias in women with placental abruption

OBJECTIVE: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. METHODS: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20,175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. RESULTS: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). CONCLUSIONS: We found that factor V Leiden is a significant risk factor for placental abruption.     

Can tissue oxygenation index (TOI) and cotside neurophysiological variables predict outcome in depressed/asphyxiated newborn infants?

BACKGROUND: Diagnostic tools of birth asphyxia provide only an uncertain prediction of neurological outcome. AIMS: To assess whether TOI and DeltaCBV, combined with a set of biochemical and neurophysiological variables, have any diagnostic and prognostic value in birth depression or asphyxia. STUDY DESIGN: Case control study at the nursery and NICU of the Padova University Children's Hospital. SUBJECTS: 22 term neonates with an Apgar score < or = 6 at 5', a 1-h umbilical artery pH value < or = 7.25 with an increased base deficit and a gestational age > or = 36 weeks; 15 healthy term infants with an Apgar score > or = 9 at 5'. OUTCOME MEASURES: Troponin I and NIRS measurements (TOI and DeltaCBV) were assessed in both groups. Blood gases, neurological evaluation, US, NIRS, EEG and SEP were evaluated in the infants with depression or asphyxia. RESULTS: Troponin I was higher in the study group than in controls (p=0.04), showing a correlation with base excess values. In the depressed/asphyxiated neonates with an abnormal outcome at 1 year, TOI rose to 80.1% vs 66.4% in controls (p=0.04) and 74.7% in infants with a normal 1-year outcome. A multiple regression model showed a significant multiple correlation coefficient, R=0.79, p<0.001, where the predictive variables significantly associated with outcome were SEP and BE. CONCLUSIONS: Troponin I is a useful short-term index of birth asphyxia or perinatal depression. An increased TOI suggests a risk of abnormal neurological outcome at 1 year. Among the cotside variables, BE and evoked potential abnormalities were the best predictors of abnormal outcome in this study.