British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Rankian will.

Otto Rank (1884-1939) served as Freud's closest partner in the psychoanalytic movement from 1906 to 1926. From 1923 on, Rank, initially with Ferenczi, focused on making analysis more therapeutic, emphasizing current experience in the session over historical exploration and interpretation. Rank settled on will as a missing factor, and wrote extensively about it after the break with Freud in 1926, when he moved to Paris. He emphasized the here-and-now, redefined "resistance" as a positive aspect of counter-will, and suggested a time limit for analysis. Ousted from analytic circles in 1930, he eventually moved to New York, continuing to treat patients and teach until his unexpected death at 55 in 1939. After decades of obscurity, Rank has gained readers and therapists whose orientation is interpersonal, client-centered, relational, humanistic, or existential. His influence on post-Freudian ego-psychology is finally being acknowledged as are his ideas about creativity, will, life-fear and death-fear, guilt, and ethics.

Embryo culture media and neonatal birthweight following IVF.

BACKGROUND: Infants conceived from IVF are at increased risk for low birthweight. Animal studies suggest that embryo culture medium influences birthweight but it is unknown whether this association exists in humans. This study examines the relationship between culture medium and birthweight following IVF. METHODS: We identified all IVF cycles with start dates between 1 January 1999 and 31 December 2008 that used autologous oocytes with resulting embryos cultured in G1.3, Global or G1.5 medium. The population was restricted to singleton deliveries following Day 3, fresh single embryo transfer, or twin deliveries following Day 3, fresh double embryo transfer, at a gestational age of ≥ 34 weeks. Only the first cycle during the study period was included for each woman. Women were excluded if the number of gestational sacs on ultrasound differed from the number of infants born. Variables were evaluated with the χ²-test or analysis of variance. Multiple linear regressions controlled for potential confounders. RESULTS: Of the 198 women with singleton deliveries, 102 embryos were cultured in G1.3, 53 in Global and 43 in G1.5 medium. Of the 303 twin deliveries, 172 pairs of embryos were cultured in G1.3, 58 in Global and 73 in G1.5 medium. No significant association between culture medium and birthweight was observed, even when controlling for potential confounders. CONCLUSIONS: This retrospective study demonstrated no significant association between embryo culture medium and birthweight following IVF. Although our careful selection of patients minimized the influence of potential confounders, further research is required to elucidate this issue with larger numbers of patients.

Brachial vessel injuries: high morbidity and low mortality injuries.

INTRODUCTION: Reports of arterial injuries from both the civilian and military arenas report the brachial artery as the most frequently injured vessel, accounting for approximately 25-33% of all peripheral arterial injuries. The brachial artery is surrounded by important peripheral nerves -the median, ulnar and radial, and also parallels the humerus and associated veins. Due to its close proximity to these structures, associated nerve and osseous injuries are frequent with residual neuropathy from such nerve injuries, often the main sources of permanent disability. MATERIALS AND METHODS: Systematic review of the literature, with emphasis in the diagnosis, treatment and outcomes of these injuries, incorporating the authors experience. CONCLUSIONS: The morbidity and mortality rates associated with brachial artery injuries depend on the cause of the injury itself, which vein or tendon is injured, and whether musculoskeletal and nerve injuries are also present. During the last 20 years, amputation associated with upper extremity arterial injuries has decreased to a rate of 3% because of advances in the treatment of shock, the use of antibiotic therapy, and increased surgical experience.

Early diagnosis of oesophageal cancer.

Squamous cell carcinoma and adenocarcinoma of the oesophagus are cancers that develop from distinct epithelial sub-types; however, they are both related to chronic inflammation of differing aetiologies. Inflammation leads to somatically inherited genetic mutations altering control of the cell cycle, DNA replication and apoptosis, which together result in autonomous and uncontrolled proliferation. These cancers have often metastasised to lymph nodes and distant organs before symptomatic presentation and therefore carry a poor prognosis. It is therefore vital to diagnose oesophageal cancer at an early stage, before the development of symptoms, when treatment can dramatically improve prognosis. Understanding the pathogenesis of these cancers is vital to guide early diagnostic strategies.

Dr Adam Zamenhof (1888-1940) and his insight into ophthalmology.

Adam Zamenhof was greatly influenced by his father, Ludwik Zamenhof, who designed the international language Esperanto. Like his father, he became an ophthalmologist and joined the Esperanto movement. He published in the field of ophthalmology and was soon chosen as head of an ophthalmology department. He subsequently became Chief of the Orthodox Jewish Hospital at Czystem in Warsaw. He was active in the leadership of the Bialystok-Warsaw Chamber of Medical Doctors. He perished in the Nazi Holocaust (Shoah) but all Zamenhof's ideals that Adam served as a doctor and social activist remain still alive.

Glutamine uptake and metabolism to N-acetylaspartylglutamate (NAAG) by crayfish axons and glia.

We have proposed that N-acetylaspartylglutamate (NAAG) or its hydrolytic product glutamate, is a chemical signaling agent between axons and periaxonal glia at non-synaptic sites in crayfish nerves, and that glutamine is a probable precursor for replenishing the releasable pool of NAAG. We report here, that crayfish central nerve fibers synthesize NAAG from exogenous glutamine. Cellular accumulation of radiolabel during in vitro incubation of desheathed cephalothoracic nerve bundles with [3H]glutamine was 74% Na(+)-independent. The Na(+)-independent transport was temperature-sensitive, linear with time for at least 4 h, saturable between 2.5 and 10 mM L-glutamine, and blocked by neutral amino acids and analogs that inhibit mammalian glutamine transport. Radiolabeled glutamine was taken up and metabolized by both axons and glia to glutamate and NAAG, and a significant fraction of these products effluxed from the cells. Both the metabolism and release of radiolabeled glutamine was influenced by extracellular Na(+). The uptake and conversion of glutamine to glutamate and NAAG by axons provides a possible mechanism for recycling and formation of the axon-to-glia signaling agent(s).

Properties of glutaminase of crayfish CNS: implications for axon-glia signaling.

Glutaminase of crayfish axons is believed to participate in recycling of axon-glia signaling agent(s). We measured the activity and properties of glutaminase in crude homogenates of crayfish CNS, using ion exchange chromatography to separate radiolabeled product from substrate. Crayfish glutaminase activity is cytoplasmic and/or weakly bound to membranes and dependent on time, tissue protein, and glutamine concentration. It resembles the kidney-type phosphate-activated glutaminase of mammals in being stimulated by inorganic phosphate and alkaline pH and inhibited by the product glutamate and by the glutamine analog 6-diazo-5-oxo-L-norleucine. During incubation of crayfish CNS fibers in Na(+)-free saline containing radiolabeled glutamine, there is an increased formation of radiolabeled glutamate in axoplasm that is temporally associated with an increase in axonal pH from about 7.1 to about 8.0. Both the formation of glutamate and the change in pH are reduced by 6-diazo-5-oxo-L-norleucine. Our results suggest that crayfish glutaminase activity is regulated by cellular changes in pH and glutamate concentration. Such changes could impact availability of the axon-glia signaling agents glutamate and N-acetylaspartylglutamate.

Involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of porcine coronary artery endothelial cells.

This study investigated the effects of the following adenosine agonists: 5;-ethylcarboxamidoadenosine (NECA), N6-cyclopentyadenosine (CPA) 2-[p-(2-carboxyethyl)]phenylamino-5;N-ethylcarboxamidoadenosine (CGS-21680), and 2-chloroadenosine (CAD) and its antagonist, 4-(2-[7-amino-2-[2-furyl]]1,2,4-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385), a selective A2A adenosine receptor antagonist, and the involvement of the K+ATP and KCa channels on the resting membrane potential (RMP) of confluent monolayers of cultured porcine coronary artery endothelial cells (PCAECs). Adenosine agonists and K+ATP channel openers (pinacidil, cromakalim) hyperpolarized cultured PCAECs. The average RMP was -32.31 +/- 1.2 mV. Adenosine agonists at 10-5 M caused a significant increase in RMP to -65.0 +/- 1.5 mV for CAD (a nonselective adenosine receptor agonist) to -75.9 +/- 1.6 mV for CGS-21680 (a selective A2A receptor agonist) and to -87.0 +/- 3.5 mV for NECA (a nonselective A1/A2A/A2B receptor agonist). Pinacidil and cromakalim at 10 microM increased the membrane potential to -76.2 +/- 1.2 mV and -75.22 +/- 0.12 mV, respectively. The hyperpolarization induced by adenosine receptor agonists and KATP openers was inhibited by an application of the K+ATP channel blocker glibenclamide (10 microM), indicating the involvement of the K+ATP channel in the adenosine-mediated hyperpolarization of PCAECs. Moreover, 1-EB10, a selective opener of the maxi-KCa channel, hyperpolarized PCAECs, and the effect of 1-EB10 was completely blocked by a selective, irreversible blocker of the high conductance KCa (maxi-K) channels (penitrem A), but it only partially blocked the effect of NECA. ZM-241385 has no effect on hyperpolarization elicited by K+ATP and KCa channel openers. However, ZM-241385 significantly blocked the hyperpolarization effect of CAD and CGS-21680. ZM-241385 partially blocked the hyperpolarizing effect of NECA, and a combination of ZM-241385 and penitrem A further blocked the hyperpolarizing effect of NECA. These results further support the involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of PCAECs.

Maternal epidural use and neonatal sepsis evaluation in afebrile mothers.

OBJECTIVE: Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women METHODS: We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (<100.4 degrees F). Neonatal sepsis evaluation generally was performed on the basis of the presence of 1 major or 2 minor criteria. Major criteria included rupture of membranes for >24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degrees F to 100.4 degrees F, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of <7 at 5 minutes. RESULTS: Infants of afebrile women with epidural analgesia were more likely to be evaluated for sepsis than infants of women without epidural (20.4% vs 8.9%), although not more likely to have neonatal sepsis. An increased risk of sepsis evaluation persisted in regression analysis (odds ratio: 3.1; 95% confidence interval: 2.0, 4.7) after controlling for confounders and was not explained by longer labors with epidural. Women with epidural were significantly more likely to have major and minor criteria for sepsis evaluation, including fetal tachycardia (4.4% vs 0.4%), rupture of membranes for >24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degrees F to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. CONCLUSIONS: Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women.

Risk factors for uterine rupture during a trial of labor after cesarean.

The rate of vaginal birth among women with a previous cesarean increased from 18.9% in 1989 to 28.3% in 1996. By 1998, the rate had decreased to 26.3% and preliminary data from 1999 suggest that the rate for that year would be even lower (23.4%). It is not known whether that decrease represents a trend related to increasing concern by providers and women about the risk of uterine rupture. Whereas the overall risk of rupture is 1%, our review demonstrates that there is considerable variation of that risk. More than one previous scar, induction of labor, a short interdelivery interval, or a history of postpartum fever during a previous cesarean may increase the risk of a uterine rupture during a trial of labor. However, there does not appear to be an increase in risk associated with low-vertical scars, and a previous vaginal delivery may be somewhat protective. Further delineation of the factors that increase the risk of uterine rupture will permit better prediction of individualized risk and identification of women for whom attempting a vaginal delivery after cesarean represents a safe option.

Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers: implications for axon-glia signaling.

Crayfish nerve fibers incubated with radiolabeled glutamate or glutamine accumulate these substrates and synthesize radioactive N-acetylaspartylglutamate (NAAG). Upon stimulation of the medial giant nerve fiber, NAAG is the primary radioactive metabolite released. Since NAAG activates a glial hyperpolarization comparable to that initiated by glutamate or axonal stimulation through the same receptor, we have proposed that it is the likely mediator of interactions between the medial giant axon and its periaxonal glia. This manuscript reports investigations of possible mechanisms for termination of NAAG-signaling activity. N-acetylaspartyl-[(3)H]glutamate was not accumulated from the bath saline by unstimulated crayfish giant axons or their associated glia during a 30-min incubation. Stimulation of the central nerve cord at 50 Hz during the last minute of the incubation dramatically increased the levels of radiolabeled glutamate, NAAG, and glutamine in the medial giant axon and its associated glia. These results indicate that stimulation-sensitive peptide hydrolysis and metabolic recycling of the radiolabeled glutamate occurred. There was a beta-NAAG-, quisqualate- and 2-(phosphonomethyl)-pentanedioic acid-inhibitable glutamate carboxypeptidase II activity in the membrane fraction of central nerve fibers, but not in axonal or glial cytoplasmic fractions. Inactivation of this enzyme by 2-(phosphonomethyl)-pentanedioic acid or inhibition of N-methyl-D-aspartate (NMDA) receptors by MK801 reduced the glial hyperpolarization activated by high-frequency stimulation. These results indicate that axon-to-glia signaling is terminated by NAAG hydrolysis and that the glutamate formed contributes to the glial electrical response in part via activation of NMDA receptors. Both NAAG release and an increase in glutamate carboxypeptidase II activity appear to be induced by nerve stimulation.

Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy.

OBJECTIVE: The purpose of this study was to evaluate whether a random urinary protein-to-creatinine ratio is a clinically useful predictor of significant proteinuria (300 mg/24 hour). STUDY DESIGN: The medical records of 138 women who completed both a random urinary protein-to-creatinine ratio and a 24-hour urine collection for the evaluation of preeclampsia were reviewed. Urine samples for the random protein-to-creatinine ratio were collected before the 24-hour urine collection. With the use of a protein level of at least 300 mg in the 24-hour urine sample as the gold standard, the sensitivity and specificity of the random protein-to-creatinine ratio for the diagnosis of significant proteinuria were determined with a range of cutoffs. RESULTS: Fifty percent of the study population had significant proteinuria. The data suggest that a cutoff below 0.14 ruled out significant proteinuria. The best cutoff of > or = 0.19 yields a sensitivity of 90% and a specificity of 70%. All of the false-negative test results had 24-hour urine protein levels below 400 mg; 13 of the 21 false-positive results had levels that ranged from 250 to 300 mg. CONCLUSION: The random urinary protein-to-creatinine ratio is strongly associated with the 24-hour total protein excretion. A level below 0.14 can rule out significant proteinuria. A best cutoff of > or = 0.19 is a good predictor of significant proteinuria. With further study, the random urinary protein-to-creatinine ratio could replace the 24-hour urine collection as a simpler, faster, more useful method for the diagnosis of significant proteinuria.

Relationship of twin zygosity and risk of preeclampsia.

OBJECTIVE: Twin gestations are known to be at higher risk for preeclampsia. One theory suggests that maternal recognition of fetal and trophoblastic tissues as foreign may be a factor. If that hypothesis is true, mothers carrying monozygous (MZ) gestations (ie a single fetal graft) might be predicted to have a lower rate of preeclampsia than those carrying dizygous (DZ) gestations. To evaluate this hypothesis, we compared the rate of preeclampsia in mothers with MZ and DZ twin gestations. STUDY DESIGN: Seven hundred sixty-eight twin deliveries from 1994 to 1999 were reviewed. Placental pathology reports were reviewed to determine the chorionic state of each placenta. Monochorionic placentas were assumed to be MZ. Dichorionic placentas were categorized as DZ if the neonates were of different sexes or different blood types. Maternal and fetal data were abstracted from the medical records. Preeclampsia was defined by standard criteria of the National Institutes of Health Working Group on High Blood Pressure. Our analysis was limited to women with pregnancies reaching at least 30 weeks of gestation where zygosity could be determined. RESULTS: Our analysis included 464 twin pregnancies, 154 MZ and 310 DZ. Among nulliparous women, the rate of preeclampsia was 15% (25/170) for DZ twins versus 20% (15/75) for MZ twins (P =.3). Among multiparous women, the rate was 8% (11/140) for DZ twins and 5% (4/79) for MZ twins (P =.4). In a logistic regression performed to control for confounding by maternal age, gestational age at delivery, assisted reproduction, and male sex, dizygotic state was associated with an odds ratio of 1.4 (95% CI = 0.5-3.9) for developing preeclampsia in nulliparous women and 1.2 in multiparous women (95% CI = 0.3-5.0). CONCLUSIONS: : These results do not support the hypothesis that zygosity affects the rate of preeclampsia in twin gestations, though the number of subjects in our study was too small to allow definitive conclusions. Larger studies are needed to evaluate this finding.

No increase in rates of early-onset neonatal sepsis by non-group B Streptococcus or ampicillin-resistant organisms.

OBJECTIVE: We assessed the impact of a risk-based approach to group B Streptococcus (GBS) prophylaxis on the rates of early-onset neonatal sepsis (EONS). STUDY DESIGN: A retrospective cohort study of neonates born at a tertiary-care hospital from 1990 to 1996 was performed. Cases of EONS were identified among neonates born in a period without GBS prophylaxis (1990-1992) and compared with those born in a period with GBS prophylaxis (1993-1996). The antibiotic susceptibility data on each organism isolated in the blood culture were obtained. RESULTS: In the period without prophylaxis, 99 cases of EONS were identified among 25,934 neonates for a rate of 3.8 per 1000 births. In the period with prophylaxis, 90 cases of EONS occurred among 34,262 neonates for a rate of 2.6 per 1000. The rate of GBS-EONS significantly decreased between the 2 periods (from 1.9 to 1.1, P =.01). There was a trend toward a decrease in the rate of EONS caused by non-GBS gram-positive organisms (from 1.2 to 0.7, P =.06). There was no significant increase in the rate of EONS caused by gram-negative or ampicillin-resistant organisms. CONCLUSIONS: A risk-based approach to GBS prophylaxis reduced the incidence of GBS-EONS at a tertiary-care hospital. This decrease was not accompanied by an increase in the incidence of EONS by non-GBS or ampicillin-resistant organisms.

Increased risk of cesarean delivery with advancing maternal age: indications and associated factors in nulliparous women.

OBJECTIVE: To investigate factors that contribute to the increased risk of cesarean delivery with advancing maternal age. STUDY DESIGN: We reviewed demographic and ante- and intrapartum variables from a data set of term, nulliparous women who delivered at Brigham and Women's Hospital in 1998 (n = 3715). RESULTS: Cesarean delivery rates increased with advancing maternal age (< 25 years, 11.6%; > or = 40 years, 43.1%). Older women were more likely to have cesarean delivery without labor (< 25 years, 3.6%; > or = 40 years, 21.1%). Malpresentation and prior myomectomy were the indications for cesarean delivery without labor that were more prevalent in our older population as compared to our younger population. Even among women with spontaneous or induced labor, cesarean delivery rates increased with maternal age (< 25 years, 8.3%; > or = 40 years, 30.6%). Cesarean delivery rates were higher with induced labor, and rates of induction rose directly and continuously with maternal age, especially the rate of elective induction. Cesarean delivery for failure to progress or fetal distress was more common among older parturients, regardless of whether labor was spontaneous or induced. Among women who underwent cesarean delivery because of failure to progress, use of oxytocin and length of labor did not vary with age. CONCLUSIONS: Older women are at higher risk for cesarean delivery in part because they are more likely to have cesarean delivery without labor. However, even among those women who labor, older women are more likely to undergo cesarean delivery, regardless of whether labor is spontaneous or induced. Part of the higher rate among older women who labor is explained by a higher rate of induction, particularly elective induction. Among women in both spontaneous and induced labor, cesarean delivery for the diagnoses of failure to progress and fetal distress was more frequent in older patients, although management of labor dystocia for these patients was similar to that for younger patients.