Evolving changes in the management of early oesophageal adenocarcinoma in a tertiary centre.

OBJECTIVES: Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed. METHODS: Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes. RESULTS: From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p<0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett's oesophagus and one patient represented with low grade dysplasia. CONCLUSIONS: This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.

Development of a novel concept (Calcigard) for activation of calcium absorption capacity and prevention of milk fever.

The background to the development of a novel concept for the prepartal activation of calcium absorption capacity as a means of preventing parturient hypocalcaemia and milk fever in grazing ruminants is described. It was hypothesised that this objective could be achieved by decreasing the bio-availability of calcium from pasture for a 3 week period. Soya bean oil was chosen as a supplement, from a number of potential binding agents, to form poorly digestible calcium soaps in the gastrointestinal tract. 28 mature twin-pregnant ewes in late pregnancy were used as assay animals to test the hypothesis, and they proved to be a sensitive experimental model for dairy cows. Following the treatment period, overnight starvation was used to challenge calcium homeostasis. Calcium absorption capacity was assessed indirectly by measuring strontium concentrations in plasma following oral dosing with strontium chloride. Strong support for the hypothesis was obtained as the 14 Treated ewes were protected from severe fasting-induced hypocalcaemia (P = 0.002), and this was associated with a greatly increased capacity of the ewes to absorb calcium. The feeding strategy developed in this experiment led to the production of a Calcigard concentrate supplement which was subsequently shown to protect cows from hypocalcaemia and milk fever, and stimulate production.

Evaluation of flexible cloth electrodes for electrodermal activity recording.

BACKGROUND: Instrument selection for recording physiological data in flight studies requires careful attention to subject comfort and non-interference with aircrew activities. Several electrode types and recording sites may be used to examine electrodermal activity (EDA). Placement of electrodes on the foot minimizes interference with physical activity and reduces motion artifacts; however, use of conventional, hard-plastic-encased metal (PEM) electrodes within a flight boot can produce discomfort and pressure-induced artifacts. HYPOTHESIS: When applied with proper electrolyte gels, thin, flexible, silver-impregnated cloth electrodes should acquire EDA signals qualitatively similar to those acquired using conventional, PEM electrodes. METHODS: EDA responses evoked by light flashes, auditory stimuli and valsalva maneuvers were recorded with cloth and PEM electrodes simultaneously from both feet of 4 male subjects. Performance of cloth vs. PEM electrodes and variability of signals recorded with the same electrode type were examined by placing pairs of selected electrodes on each foot of the subjects. Placements were balanced with respect to age and handedness of the subject and the number of trials with each electrode type placed on the left or right foot. RESULTS: Qualitatively similar signals were recorded with cloth and PEM electrodes. Cloth electrodes showed more variability between electrodes of the same type. CONCLUSION: For EDA recording, cloth electrodes can perform at least as well as PEM electrodes, making it practical to take advantage of the cloth electrodes' flexibility and lower profile.

The effect of season and monensin sodium on the digestive characteristics of autumn and spring pasture fed to sheep.

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, beta-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P < 0.05), cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05), hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P < 0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid.

A novel nutritional strategy to prevent milk fever and stimulate milk production in dairy cows.

AIMS: To assess the efficacy of a feed supplement designed to reduce the dietary availability of calcium when fed during the last 2-3 weeks of pregnancy, on the incidence of postparturient hypocalcaemia (milk fever) and on milksolids (MS) production in pasture-fed dairy cows in early lactation. METHODS: In Experiment 1, late-pregnant Holstein/Friesian cows, 4-10 years old, grazing pasture, were either fed the supplement (1 kg/cow/day) for 2-4 weeks prior to calving (n=11) or no supplement (n=10). Plasma calcium concentrations were measured immediately before and after a 20 h fast intended to induce hypocalcaemia at the end of this period, 1-7 days before the cows calved. In Experiment 2, mixed-breed dairy cows, 3-10 years old in 7 commercial dairy herds were fed the same supplement (1 kg/cow/day) for 1-3 weeks immediately prior to calving (n=565) or no supplement (n=614), and incidences of clinical milk fever and MS production at 6-9 weeks post calving were compared between groups. RESULTS: In Experiment 1, plasma calcium concentrations were higher (p=0.01) in supplemented than in non-supplemented cows after fasting, indicating reduced susceptibility to fasting-induced hypocalcaemia. In Experiment 2, the incidence of milk fever was lower (6.4% vs 17.1%, p=0.001) and MS production was higher (p=0.01) in supplemented than in non-supplemented cows. CONCLUSIONS: These preliminary results demonstrate that feeding a supplement designed to reduce dietary calcium availability for 2-4 weeks immediately prior to calving reduced the susceptibility of cows to fasting-induced hypocalcaemia, reduced the incidence of clinical milk fever and increased MS production in early lactation. CLINICAL RELEVANCE: The concept and product reported here have potential to provide dairy farmers with a practical means to prevent hypocalcaemia and improve milk production during early lactation.

Stimulation of calcium absorption and reduction in susceptibility to fasting-induced hypocalcaemia in pregnant ewes fed vegetable oil.

AIM: To test the hypothesis that susceptibility to fasting-induced hypocalcaemia could be reduced by prior stimulation of the ability of late-pregnant ewes to absorb calcium (Ca) from the gastrointestinal tract (GIT) by feeding a vegetable oil supplement. The supplement was expected to decrease the availability of the Ca supplied from a pasture diet, and stimulate the animals' homeostatic system. METHODS: Mature ewes pregnant with twins (n=28) and grazing at pasture, were randomly allocated to Treated or Control groups, 6 weeks prior to their expected date of parturition (Day 0). Treated ewes (n=14) were drenched with 25 ml soya bean oil twice daily for 3 weeks. Plasma Ca concentrations were determined on Days 0, 8, and immediately before and after a 20-hour fast that began on Day 21, which was intended to simulate the reduced feed intakes that occur on the day of parturition. An index of the ewes' ability to absorb Ca from the GIT was obtained using orally dosed strontium (Sr) as a tracer and the extent of Ca mobilisation from bone was assessed by measuring hydroxyproline concentrations in plasma before fasting on Day 21. RESULTS: Plasma Ca concentrations were significantly higher in Treated than Control ewes after fasting (p0.001). The Ca absorption index was also higher in Treated than Control ewes at the end of the 3-week treatment period (p=0.014), but degree of bone mobilisation assessed by concentration of hydroxyproline in plasma did not differ significantly between groups. CONCLUSION: Susceptibility of late-pregnant ewes to fasting-induced hypocalcaemia was reduced using a soya bean oil supplement. The inclusion of one or more dietary ingredients capable of binding or forming complexes specifically with Ca in the diet of late pregnant ruminants may provide a novel, practical method of reducing periparturient hypocalcaemia.

The eag family of K+ channels in Drosophila and mammals.

Mutations of eag, first identified in Drosophila on the basis of their leg-shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons. The encoded EAG polypeptide is related both to voltage-gated K+ channels and to cyclic nucleotide-gated cation channels. Homology screens identified a family of eag-related channel polypeptides, highly conserved from nematodes to humans, comprising three subfamilies: EAG, ELK, and ERG. When expressed in frog oocytes, EAG channels behave as voltage-dependent, outwardly rectifying K(+)-selective channels. Mutations of the human eag-related gene (HERG) result in a form of cardiac arrhythmia that can lead to ventricular fibrillation and sudden death. Electrophysiological and pharmacological studies have provided evidence that HERG channels specify one component of the delayed rectifier, IKr, that contributes to the repolarization phase of cardiac action potentials. An important role for HERG channels in neuronal excitability is also suggested by the expression of these channels in brain tissue. Moreover, mutations of ERG-type channels in the Drosophila sei mutant cause temperature-induced convulsive seizures associated with aberrant bursting activity in the flight motor pathway. The in vivo function of ELK channels has not yet been established, but when these channels are expressed in frog oocytes, they display properties intermediate between those of EAG- and ERG-type channels. Coexpression of the K(+)-channel beta subunit encoded by Hk with EAG in oocytes dramatically increases current amplitude and also affects the gating and modulation of these currents. Biochemical evidence indicates a direct physical interaction between EAG and HK proteins. Overall, these studies highlight the diverse properties of the eag family of K+ channels, which are likely to subserve diverse functions in vivo.

EEG power changes during a multiple level memory retention task.

EEG changes related to the amount of information held in memory during a 4-s retention period were studied. The predictability of the amount of information held in memory was varied. In the weighted condition, 60% of the trials contained only one item and the remaining 40% of the trials were evenly distributed between trials containing 3, 5, 7, or 8 items. In the random condition, the levels were equally represented and randomly presented. In the blocked condition the levels were equally represented but presented in five blocks containing only items from one of the levels. Initial widespread decreases in alpha band power were followed by increased activity in all three conditions. The more difficult of the five levels produced decreased alpha activity in more localized posterior left hemisphere sites. This suggests two alpha mechanisms, one associated with task engagement and the other related to the cognitive demands regardless of the presentation context. Theta band power increased over frontal scalp, and to a lesser extent over left parietal and temporal areas and bilateral occipital sites, during only the weighted condition. These changes were uniform over the entire retention period. Beta 2 activity was also influenced by the task difficulty and the time course of the retention period in the two conditions. Beta 2 activity resembled both alpha and theta in that in levels 1, 2 and 3 it acted like alpha with increasing power over time at numerous widespread sites while the higher difficulty levels showed higher power at the beginning of the retention period and then decreased.

Guided versus blind liver biopsy for chronic hepatitis C: clinical benefits and costs.

BACKGROUND/AIMS: Our objectives were: (1) to assess the clinical benefits and costs of performing ultrasound-guided liver biopsy with an automated needle compared to blind biopsy with a conventional Trucut needle in patients with chronic hepatitis C; (2) to compare the histological yield of automated needles with Trucut needles. METHODS: We prospectively studied 166 patients with hepatitis C virus who underwent either ultrasound-guided biopsy using automated ASAP needles or blind biopsy using conventional Trucut needles. Both groups were matched for age, sex, cirrhosis, needle gauge and operator experience. Patient tolerance, complications and histological adequacy were assessed. In a separate in vitro study, we assessed the histological adequacy of liver biopsy specimens obtained using automated and Trucut needles from 10 fresh autopsy cases. RESULTS: Ultrasound-guided biopsy caused significantly less biopsy pain (36.4% vs. 47.3%; p < 0.0001) and significantly less pain-related morbidity (1.8% vs. 7.7%, p < 0.05). Although, there was no significant difference in diagnostic yield between guided and blind biopsy (98% vs. 94%, p = 0.15), 3 blind biopsies (3.3%), including 2 which yielded extra-hepatic tissue, had to be repeated. The additional expense of performing guided liver biopsy with automated needles was 42 Irish Pounds per patient. In vitro, automated ASAP 15G needles provided liver specimens comparable to Trucut 15G needles and had the highest histopathologic score among the automated needles assessed. CONCLUSIONS: Even in the absence of major complications, ultrasound-guided liver biopsy with an automated needle in HCV patients is safer, more comfortable and only marginally more expensive than blind Trucut biopsy.

Electrophysiological, behavioral, and subjective indexes of workload when performing multiple tasks: manipulations of task difficulty and training.

This study examined whether alpha event-related desynchronization (ERD) and theta event-related synchronization (ERS) could successfully measure changes in cognitive workload and training while an operator was engaged in a continuous, interactive, control task(s). Alpha 1 (8-10 Hz) ERD, alpha 2 (10-12 Hz) ERD, and theta (3-7 Hz) ERS were determined for a communications event that occurred during multiple task workload conditions or as a single task. Other measures (alpha and theta EEG power, heart rate, respiration, eye blinks, behavioral performance, and subjective workload ratings) were also evaluated. Results showed that alpha 2 EEG, heart rate, behavioral, and subjective measures were sensitive to changes in workload in the multiple tasks. In addition, eye blink rate and behavioral measures were sensitive to training. Alpha ERD and theta ERS were not sensitive to workload and training in our interactive, multiple task environment. However, they were effective indexes of cognitive/behavioral demands within an interactive single task.

Digitized mammograms: a preliminary clinical evaluation and the potential for telemammography.

We performed a preliminary clinical evaluation of digitized mammograms to assess whether digital images suitable for telemammography could be obtained. Thirty mammograms were digitized at a resolution of 4000 x 4000 pixels and 12 bit/pixel. The series contained 17 carcinomas in 16 patients. Five consultant radiologists reported both the original mammograms and the digitized images. There was agreement between the reports of the mammograms and the digitized images in relation to whether a suspicious lesion was present or not in 95% of cases. No study considered benign on viewing the film images was interpreted as malignant on reporting the digitized images. This suggests that film digitizers may allow a digital image of a mammogram of acceptable quality for telemammography to be obtained in the absence of a purpose-built digital mammography system.

CT and MRI appearances of a thoracic chordoma.

A case of a chordoma in the thoracic spine is presented. This is a very rare tumour in this location and should be considered in the differential diagnosis of any posterior mediastinal mass. The appearances on CT and MRI were similar to chordomas described in other locations. On T2-weighted images septae of low signal intensity radiated throughout the large high-signal mass. This feature may be of use in differentiating chordomas from other posterior mediastinal masses.

Modulation of a calcium-sensitive nonspecific cation channel by closely associated protein kinase and phosphatase activities.

Regulation of nonspecific cation channels often underlies neuronal bursting and other prolonged changes in neuronal activity. In bag cell neurons of Aplysia, it recently has been suggested that an intracellular messenger-induced increase in the activity of a nonspecific cation channel may underlie the onset of a 30-min period of spontaneous action potentials referred to as the "afterdischarge. " In patch clamp studies of the channel, we show that the open probability of the channel can be increased by an average of 10. 7-fold by application of ATP to the cytoplasmic side of patches. Duration histograms indicate that the increase is primarily a result of a reduction in the duration and percentage of channel closures described by the slowest time constant. The increase in open probability was not observed using 5'-adenylylimidodiphosphate, a nonhydrolyzable ATP analog, and was blocked in the presence of H7 or the more specific calcium/phospholipid-dependent protein kinase C (PKC) inhibitor peptide(19-36). Because the increase in activity observed in response to ATP occurred without application of protein kinase, our results indicate that a kinase endogenous to excised patches mediates the effect. The effect of ATP could be reversed by exogenously applied protein phosphatase 1 or by a microcystin-sensitive phosphatase also endogenous to excised patches. These results, together with work demonstrating the presence of a protein tyrosine phosphatase in these patches, suggest that the cation channel is part of a regulatory complex including at least three enzymes. This complex may act as a molecular switch to activate the cation channel and, thereby, trigger the afterdischarge.

Interaction of the K channel beta subunit, Hyperkinetic, with eag family members.

Assembly of K channel alpha subunits of the Shaker (Sh) family occurs in a subfamily specific manner. It has been suggested that subfamily specificity also applies in the association of beta subunits with Sh channels (Rhodes, K. J., Keilbaugh, S. A., Barrezueta, N. X., Lopez, K. L., and Trimmer, J. S. (1995) J. Neurosci. 15, 5360-5371; Sewing, S., Roeper, J. and Pongs, O. (1996) Neuron 16, 455-463; Yu, W., Xu, J., and Li, M. (1996) Neuron 16, 441-453). Here we show that the Drosophila beta subunit homologue Hyperkinetic (Hk) associates with members of the ether go-go (eag), as well as Sh, families. Anti-EAG antibody coprecipitates EAG and HK indicating a physical association between proteins. Heterologously expressed Hk dramatically increases the amplitudes of eag currents and also affects gating and modulation by progesterone. Through their ability to interact with a range of alpha subunits, the beta subunits of voltage-gated K channels are likely to have a much broader impact on the signaling properties of neurons and muscle fibers than previously suggested.

ERP components elicited in response to warning stimuli: the influence of task difficulty.

A series of experiments were conducted to systematically evaluate the relative contributions of task difficulty and stimulus probability to P300 amplitudes. Scalp event-related potentials (ERPs) were recorded and the topographic distributions were evaluated during a multi-level cognitive task with an antecedent warning. In three separate studies, task difficulty (five levels), probability or expectedness (10-60%), and randomness (random or blocked presentation) were manipulated. Response accuracy, subjective ratings, and reference-free averages of the P300 components elicited by the warning stimuli were evaluated. Statistical analysis indicated that significantly larger P300s were associated with the more difficult task warnings except when memory tasks were presented in a blocked design, suggesting that neither task difficulty nor probability alone can account for variations in the P300 in a multi-level task scenario. Results are discussed with regard to adaptation-level theory.

A comparison of heart rate, eye activity, EEG and subjective measures of pilot mental workload during flight.

BACKGROUND: Mental workload is a major consideration in the design and operation of modern aircraft systems. Objective measures of mental workload that are sensitive and diagnostic are required to meet the needs of both pilots and designers. Due to the multifaceted nature of these complex mental demands multiple measures are required. HYPOTHESIS: Psychophysiological and subjective measures provide unique information about mental workload during flight. METHODS: Cardiac, eye, brain and subjective data were collected during an actual flight scenario designed to provide tasks which required different piloting skills at several levels of mental workload. RESULTS: Heart rate was sensitive to the demands of flight but not diagnostic with regard to determining the cause of the workload. Heart rates increased during take offs and landings and to an intermediate level during instrument flight rules (IFR) segments. By showing sensitivity to only the visual demands of the various segments of flight eye activity was more diagnostic. The theta band of the EEG demonstrated increased power during those flight segments which required inflight mental calculations. The subjective measures showed trends suggesting different levels of mental demand but demonstrated few statistically significant differences. CONCLUSIONS: Multiple measures, especially psychophysiological measures, provide a comprehensive picture of the mental demands of flight. The measures used in this study were shown to provide unique, non-overlapping information. Because of the continuous nature of the psychophysiological data it may be possible to develop systems which provide on-line monitoring of mental workload that can provide feedback to the pilot and aircraft systems.

Renal ultrasonic findings in sulphadiazine-induced renal failure.

The increased incidence of cerebral toxoplasmosis in AIDS has led to a resurgence in the use of sulphadiazine. One complication of this is acute renal failure secondary to sulphadiazine-induced crystalluria. Three cases are described which demonstrate a spectrum of ultrasound findings ranging from echogenic foci in the renal parenchyma to echogenic material in both dilated and non-dilated collecting systems. In patients with AIDS having sulphadiazine treatment, these ultrasonic findings suggest that sulphadiazine is the cause of the renal failure.

Identification and characterization of a Ca(2+)-sensitive nonspecific cation channel underlying prolonged repetitive firing in Aplysia neurons.

The afterdischarge of Aplysia bag cell neurons has served as a model system for the study of phosphorylation-mediated changes in neuronal excitability. The nature of the depolarization generating the afterdischarge, however, has remained unclear. We now have found that venom from Conus textile triggers a similar prolonged discharge, and we have identified a slow inward current and corresponding channel, the activation of which seems to contribute to the onset of the discharge. The slow inward current is voltage-dependent and Ca(2+)-sensitive, reverses at potentials slightly positive to O mV, exhibits a selectivity of K approximately equal to Na >> Tris > N-methyl-D-glucamine (NMDG), and is blocked by high concentrations of tetrodotoxin. Comparison of these features with those observed in channel recordings provides evidence that a Ca(2+)-sensitive, nonspecific cation channel is responsible for a slow inward current that regulates spontaneous repetitive firing and suggests that modulation of the cation channel underlies prolonged changes in neuronal response properties.