Conscious sedation for endoscopic and non-endoscopic interventional procedures: meeting patients' expectations, missing the standard.
Explore the source record for details and available documents.
Procedural Sedation↗
Biomedical subjects
J Hancock
Publications and source records attributed to J Hancock.
Can mainstream services learn from male only sexual health pilot projects?
Over the past decade a number of community based sexual health projects aimed solely at young men have proved to be very successful at attracting young men into genitourinary medicine services. These projects are often short term funded and under evaluated so it isn't clear exactly how successful they are and why this might be so. These projects should be carefully evaluated and examined to elicit factors, either unique or common in nature, which could be utilised by mainstream sexual health services wishing to develop work with young men. There are many barriers to this happening in mainstream services, some being resource and time problems and others to do with values of staff and lack of quality training. The article looks at practical ways that working with men and the skills and confidence of staff can be improved in mainstream settings while recognising that much of what needs to be done to support the needs of young men must take place in the planning and commissioning stage of services.
Age Factors↗
Level of minimal residual disease prior to haematopoietic stem cell transplantation predicts prognosis in paediatric patients with acute lymphoblastic leukaemia: a report of the Pre-BMT MRD Study Group.
Explore the source record for details and available documents.
Child↗
Inhibition affecting RQ-PCR-based assessment of minimal residual disease in acute lymphoblastic leukemia: reversal by addition of bovine serum albumin.
Explore the source record for details and available documents.
Acute Disease↗
Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL.
We have retrospectively investigated the relationship between the level of minimal residual disease (MRD) detected in bone marrow taken prior to conditioning therapy and outcome following stem cell transplantation for high risk childhood ALL. Forty-one patients, in whom both a molecular marker of MRD and sufficient archival material was available, were included in the study. All were in remission at BMT: eight in CR1, 32 in CR2 and five in greater than CR2. MRD was measured by PCR amplification of antigen receptor gene rearrangements and clone-specific oligoprobing, the median sensitivity of detection being one leukaemic cell in 10000 normals. Results were classified as high-level positive (if a clonal band was evident after electrophoresis), low-level positive (if MRD was detected only after oligoprobing) and negative. MRD was detected at high levels in 17 patients, at low levels in 10 patients and 14 patients were MRD negative at the time of transplant. The 5-year event-free survival for these groups was 23%, 48% and 78%, respectively (P = 0.022). Limited multivariate analysis confirmed the significance of MRD (P = 0.0095) vs CR status, donor type, sex, immunophenotype and acute GvHD. This study confirms the strong relationship between MRD level and outcome following allogeneic transplantation. In contrast to a previous study we observed that a minority of children with high-level pre-BMT MRD can enter long lasting remission. The possible role for acute GVHD coupled with a graft-versus-leukaemia effect in the clearance of high level MRD in patients with ALL is discussed.
Acute Disease↗
Generation of a humanised single chain Fv (Scfv) derived from the monoclonal Eric-1 recognising the human neural cell adhesion molecule.
BACKGROUND: Murine monoclonal antibody (MoAb) ERIC-1 recognises an epitope on the neural cell adhesion molecule (NCAM) whose expression in paediatric and adult tissues is confined mainly to the brain, peripheral nerve, and adrenal medulla. Anti-NCAM antibodies have been used for the treatment and diagnosis of a number of tumours, including neuroblastoma. However, whole antibody exhibits poor penetration into solid tumour deposits and rapid systemic clearance upon repeated administration due to development of a human antimouse antibody (HAMA) response. PROCEDURE: To overcome these problems, recombinant DNA techniques have been used to humanise and assemble the ERIC-1 immunoglobulin variable heavy (VH) and light (VL) chains into a single chain Fv (scFv). RESULTS: Three humanised scFv clones were identified which differ from the predicted humanised sequence by occasional amino acid changes, but these maintain the same specificity as the original ERIC-1 MoAb. CONCLUSIONS: The humanised scFv may prove to be a useful reagents in the treatment and diagnosis of a variety of neuroectodermal tumours and can clearly form a suitable template for the generation of a fully humanised ERIC-1 MoAb.
Amino Acid Sequence↗
Maternal left ventricular mass and diastolic function during pregnancy.
OBJECTIVE: To evaluate changes in left ventricular mass and diastolic function during normal pregnancy. METHODS: This was a cross-sectional study of 125 pregnant women at 9-42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the maternal left ventricle and left atrium was performed. RESULTS: During pregnancy left ventricular mass increased by 52%. There was an increase in left ventricular end-diastolic and end-systolic diameters (12% and 20%, respectively), left ventricular posterior wall diameter during diastole and systole (22% and 13%, respectively) and left intraventricular septum during diastole and systole (15% and 19%, respectively). Mitral valve A-wave maximum velocity increased during pregnancy by 19%, while mitral valve E-wave maximum velocity and the ratio of E-wave/A-wave velocities increased early in pregnancy by about 14% and 6%, respectively, with a subsequent decline to 4% and 10%, respectively, below non-pregnant levels. CONCLUSION: Left ventricular mass increases during pregnancy, while left ventricular diastolic function, as demonstrated by the changes in mitral valve flow velocities, increases in the first two trimesters but declines in the third trimester.
Adult↗
Effects of aging on left atrial reservoir, conduit, and booster pump function: a multi-institution acoustic quantification study.
OBJECTIVE: To assess the feasibility of measuring left atrial (LA) function with acoustic quantification (AQ) and then assess the effects of age and sex on LA reservoir, conduit, and booster pump function. PATIENTS AND SETTING: 165 subjects without cardiovascular disease, 3-79 years old, were enrolled by six tertiary hospital centres. INTERVENTIONS: Continuous LA AQ area data were acquired and signal averaged to form composite waveforms which were analysed off-line. MAIN OUTCOME MEASURES: Parameters of LA performance according to age and sex. RESULTS: Signal averaged LA waveforms were sufficiently stable and detailed to allow automated analysis in all cases. An age related increase in LA area was noted. LA reservoir function did not vary with age or sex. All parameters of LA passive and active emptying revealed a significant age dependency. Overall, the passive emptying phase accounted for 66% of total LA emptying ranging from 76% in the youngest to 44% in the oldest decade. LA contraction accounted for 34% of atrial emptying in all subjects combined with the older subjects being more dependent on atrial booster pump function. When adjusted for atrial size, there were no sex related differences in LA function. CONCLUSIONS: LA reservoir, conduit, and booster pump function can be assessed with automated analysis of signal averaged LA area waveforms. As LA performance varies with age, establishment of normal values should enhance the evaluation of pathologic states in which LA function is important.
Acoustics↗
Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.
The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.
Adrenergic beta-Agonists↗
Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats.
Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.
Animals↗
The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue.
Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are used extensively as inhibitors of NADH-ubiquinone reductase and NADPH oxidase activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported. The IC(50) of neutrophil superoxide production, measured using the superoxide dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75 microM, while 50% inhibition of mitochondrial respiration, measured by the rate of oxygen uptake using a Clark type oxygen electrode, was at approximately 20 microM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was also studied, giving a K(i) of 0.2 microM. Inhibition of nitric oxidase synthase (NOS: from rat brain) by 0.2 microM phenoxaiodonium was equivalent to 1 mM N(G)-nitro-L-arginine methyl ester HCl (L-NAME), that is total abolition of activity. We conclude that phenoxaiodonium is an extremely good inhibitor of flavo-enzymes, but like diphenylene iodonium and iodonium diphenyl, will be of limited use as a pharmacological tool for the elucidation of the involvement of such enzymes in specific cellular functions.
Animals↗
Normal values of regional left ventricular endocardial motion: multicenter color kinesis study.
Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age- and gender-related differences. Normal limits of all ejection and filling indexes were in a narrow range (< or =25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in five- and twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 +/- 2.0 to 6.4 +/- 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction.
Adolescent↗
Nursing the preterm surgical neonate.
The preterm neonate's response to surgery manifests in all body systems. Necrotising Enterocolitis (NEC) is an acute gastro-intestinal emergency requiring surgical intervention. Severe NEC may require the removal of infarcted bowel. Examining the response to surgery in the preterm neonate with NEC offers nurses a rationale for their post-operative care. Both physiological and psychological responses need to be understood in the light of family centred care.
Breast Feeding↗
Organoapatite growth on an orthopedic alloy surface.
We report here a method to coat orthopedic metals with the artificial bone material organoapatite. The growth of organoapatite on titanium alloy surfaces of foils and porous cylinders involves sequential preadsorption of poly(L-lysine) and poly(L-glutamic acid) on metal, followed by exposure to organoapatite-precipitating solutions. The organoapatite characterization of the coating was carried out by transmission electron microscopy, electron diffraction, scanning electron microscopy, energy-dispersive X-ray scattering, powder X-ray diffraction, FT-IR, and elemental analysis. The preadsorbed poly(amino acids) in the form of a self-assembled bilayer of oppositely charged macromolecules can lead to a surface coverage of titanium alloy in the range of 70-90%. The deposition mechanisms could involve the surface capture of embryonic crystals and the nucleation of apatite on the bilayer. Bioabsorbable organoapatite could serve as a tissue-engineering scaffold for bone regeneration into porous implants.
Apatites↗
Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure.
For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.
Acute Kidney Injury↗
Evaluation of myocardial, hepatic, and renal perfusion in a variety of clinical conditions using an intravenous ultrasound contrast agent (Optison) and second harmonic imaging.
OBJECTIVE: To assess the potential of intravenous Optison, a second generation ultrasound contrast agent, and various ultrasound imaging modes to determine myocardial, kidney, and liver perfusion in normal subjects and patients with left ventricular dysfunction or chronic pulmonary disease together with renal or hepatic dysfunction. METHODS: Five normal subjects and 20 patients underwent grey scale echocardiographic imaging of myocardium, kidney, and liver during 505 intravenous injections of Optison. Images were assessed qualitatively by two independent observers and quantitatively using video densitometry to determine the peak contrast enhancement effect. RESULTS: Qualitative analysis showed that intermittent harmonic imaging was superior to either conventional fundamental or continuous harmonic imaging for all organs. Quantitative analysis showed that the peak change in echocardiographic intensity v baseline during continuous harmonic imaging was 11 units for myocardium (p < 0.03), 7 units for kidney (NS), and 14 units for liver (p < 0.05). During intermittent harmonic imaging the peak change was significantly greater, being 33 units for myocardium (p < 0.0001), 24 units for kidney (p < 0.0002), and 16 units for liver (p < 0.001). CONCLUSIONS: Organ tissue perfusion can be demonstrated following intravenous injection of Optison, particularly when used in combination with intermittent harmonic imaging techniques. This contrast agent is effective in a variety of clinical conditions.
Adult↗
Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing.
When the human glucocorticoid receptor (GR) was first sequenced, a predominant form (GRalpha) and a minor variant (GRbeta) were identified. In the present communication, we describe a new variant of the glucocorticoid receptor (GRgamma) in which, as a result of alternative splicing, three bases are retained from the intron separating exons 3 and 4. These three bases code for an additional amino acid (arginine) in the DNA binding domain of the receptor. Insertion of arginine at this site has previously been shown to decrease transcriptional activation by the GR to 48% that of GRalpha. Analysis of cDNA from different tissues shows that the novel form is widely expressed at a relatively high level (between 3.8 and 8.7% of total GR).
Alternative Splicing↗
Inhibition of hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries by diphenyleneiodonium (DPI).
The NADPH oxidase inhibitor, diphenyleneiodonium (DPI), is known to selectively inhibit hypoxic pulmonary vasoconstriction (HPV) in isolated rat and rabbit lungs. We have investigated whether DPI has similar effects in rat pulmonary arteries in vitro. Vessels (n=38, internal diameters 327+/-41 microM) were mounted in an automated myograph and preconstricted with prostaglandin F2alpha (PGF2alpha, 5 microM) before an acute hypoxic challenge. The effects of DPI (10 microM), or the vehicle DMSO, were studied on the first contractile phase of HPV. DPI (10 microM) was found to significantly inhibit HPV; 1.83+/-0.42 mN/mm (pre-DPI) compared to 0.11+/-0.22 mN/mm (post-DPI,P<0.01). However, the vehicle DMSO (0.2%) also resulted in a reduction of HPV, although this was significantly different from inhibition via DPI (P<0.05), implying a DPI-sensitive component. The effects of DPI (0.1-300 microM) were also studied on the second contractile phase of HPV. DPI (300 microM) caused a significant reversal of 45% (0.50-0.27 mN/mm) compared to 9% reversal (0.38-0.35 mN/mm) seen with DMSO (P<0.0001). The fact that an inhibitor of NADPH oxidase, the enzyme responsible for producing reactive oxygen species from oxygen, attenuated the pulmonary vascular response to hypoxia, may indicate that this, or a similar, enzyme is involved in oxygen sensing.
Animals↗