PubMed Health⌕ Search

Biomedical subjects

N Hughes

Publications and source records attributed to N Hughes.

At least 19 recordsLinked to original sources
PubMed2000

Adults with terminal illness: a literature review of their needs and wishes for food.

Food refusal can be a source of conflict between dying people and their caregivers. This review examines: the nature and purpose of food; some reasons for and implications of anorexia in terminal illness; ethical principles underpinning responses to declining appetite and food refusal; social transactions between dying people and their caregivers in relation to needs and wishes for food; and the need for further empirical research. The nature and purpose of food in human societies has been studied extensively by anthropologists but the knowledge gained is not often imported into health care practice, where eating is seen from a medical rather than an anthropological perspective. Food refusal may be a consequence of anorexia which is the result of physiological or psychological changes or it may be a deliberate choice in acceptance of impending death. Ethical principles underpinning responses to declining appetite and food refusal have been studied extensively and clear guidance obtained about what would be appropriate behaviour in given circumstances. There is little published empirical work on social transactions between dying people and their caregivers in relation to needs and wishes for food. As the contribution made to effective care-giving by high-quality interpersonal relationships is widely recognized, further knowledge about how best to sustain such relationships in these important circumstances would be useful. Moreover, as such interpersonal relationships often occur in an institutional context, it may be that more can be learnt from close examination of social transactions about how best to structure organizational processes to maximize autonomy and comfort for patients at the end of life. Further research is indicated.

Anorexia↗
PubMed1999

Aorto-left renal vein fistula: is there a place for endovascular management?

PURPOSE: To describe the endovascular treatment of an aorto-left renal vein fistula. METHODS AND RESULTS: A 77-year-old man with multiple comorbidities presented with low back pain, hematuria, cyanosis, and a pulsatile abdominal mass. Imaging confirmed a 7-cm abdominal aortic aneurysm with a contained rupture into the left renal vein. Owing to the patient's high surgical risk, a Talent Endoluminal Stent-Graft was implanted to satisfactorily exclude the aneurysm. Hemodynamic stability and normal renal function were restored; however, continued perfusion of the sac prompted an attempt to percutaneously repair the renal vein defect. This effort failed, so open laparotomy was necessary. CONCLUSIONS: Although total endovascular management was not successful in this case, the initial use of a minimally invasive approach allowed the patient's clinical status to improve and lower the risk of subsequent surgery.

Aged↗
PubMed1998

Acute airway obstruction during spinal anaesthesia for caesarean section.

A 30-year-old primiparous Caucasian woman with known placenta praevia required an emergency caesarean section for a mild antepartum haemorrhage at the onset of spontaneous term labour. Following intravenous prehydration with 500 ml gelatin colloid (Haemaccel trade mark ), spinal anaesthesia was induced in the sitting position with 2.6 ml of 0.5% hyperbaric bupivacaine (13 mg). The patient was then placed in the recumbent position with left lateral tilt, whereupon she suddenly became dyspnoeic. A generalized erythematous urticarial rash with associated facial, periorbital, glossal and perioral oedema became evident. Although maternal blood pressure remained within normal limits, emergency conversion to general anaesthesia with tracheal intubation was necessary to secure the airway. Laryngoscopy revealed gross submucosal, epiglottic and pharyngeal oedema, characteristics of the syndrome of angioneurotic oedema, which may complicate an anaphylactoid reaction. After the airway was secured with a cuffed endotracheal tube, caesarean section proceeded uneventfully and a healthy male infant was delivered. Maternal facial and airway oedema subsided and extubation was performed in intensive care 2 h later. Life-threatening airway obstruction often accompanies angioneurotic oedema. Since parturients have a higher incidence of difficult airway management than the general population, anaphylactoid reactions presenting as angioneurotic oedema pose a particular challenge for the anaesthetist. The lower incidence of allergy associated with hydroxyethyl starch (Hetastarch) may make it a more appropriate choice of colloid in this setting. However, the balance of evidence now suggests that vasopressors, particularly ephedrine, are superior to fluids for maintenance of blood pressure during regional anaesthesia for caesarean section.

Journal Article↗
PubMed1997

Evidence that galactanase A from Pseudomonas fluorescens subspecies cellulosa is a retaining family 53 glycosyl hydrolase in which E161 and E270 are the catalytic residues.

A genomic library of Pseudomonas fluorescens subsp. cellulosa DNA was screened for galactanase-positive recombinants. The nine galactanase positive phage isolated contained the same galactanase gene designated galA. The deduced primary structure of the enzyme (galactanase A; GalA) encoded by galA had a Mr of 42 130 and exhibited significant sequence identity with a galactanase from Aspergillus aculeatus, placing GalA in glycosyl hydrolase family 53. The enzyme displayed properties typical of an endo-beta1, 4-galactanase and exhibited no activity against the other plant structural polysaccharides evaluated. Analysis of the stereochemical course of 2,4-dinitrophenyl-beta-galactobioside (2,4-DNPG2) hydrolysis by GalA indicated that the galactanase catalyzes the hydrolysis of glycosidic bonds by a double displacement general acid-base mechanism. Hydrophobic cluster analysis (HCA) suggested that family 53 enzymes are related to the GH-A clan of glycosyl hydrolases, which have an (alpha/beta)8 barrel structure. HCA also predicted that E161 and E270 were the acid-base and nucleophilic residues, respectively. Mutants of GalA in which E161 and E270 had been replaced with alanine residues were essentially inactive against galactan. Against 2,4-DNPG2, E161A exhibited a much lower Km and kcat than native GalA, while E270A was inactive against the substrate. Analysis of the pre-steady-state kinetics of 2,4-DNPG2 hydrolysis by E161A showed that there was an initial rapid release of 2,4-dinitrophenol (2,4-DNP), which then decayed to a slow steady-state rate of product formation. No pre-steady-state burst of 2,4-DNP release was observed with the wild-type enzyme. These data are consistent with the HCA prediction that E161 and E270 are the acid-base and nucleophilic catalytic residues of GalA, respectively.

Amino Acid Sequence↗
PubMed1997

Key residues in subsite F play a critical role in the activity of Pseudomonas fluorescens subspecies cellulosa xylanase A against xylooligosaccharides but not against highly polymeric substrates such as xylan.

In a previous study crystals of Pseudomonas fluorescens subspecies cellulosa xylanase A (XYLA) containing xylopentaose revealed that the terminal nonreducing end glycosidic bond of the oligosaccharide was adjacent to the catalytic residues of the enzyme, suggesting that the xylanase may have an exo-mode of action. However, a cluster of conserved residues in the substrate binding cleft indicated the presence of an additional subsite, designated subsite F. Analysis of the biochemical properties of XYLA revealed that the enzyme was a typical endo-beta1,4-xylanase, providing support for the existence of subsite F. The three-dimensional structure of four family 10 xylanases, including XYLA, revealed several highly conserved residues that are on the surface of the active site cleft. To investigate the role of some of these residues, appropriate mutations of XYLA were constructed, and the biochemical properties of the mutated enzymes were evaluated. N182A hydrolyzed xylotetraose to approximately equal molar quantities of xylotriose, xylobiose, and xylose, while native XYLA cleaved the substrate to primarily xylobiose. These data suggest that N182 is located at the C site of the enzyme. N126A and K47A were less active against xylan and aryl-beta-glycosides than native XYLA. The potential roles of Asn-126 and Lys-47 in the function of the catalytic residues are discussed. E43A and N44A, which are located in the F subsite of XYLA, retained full activity against xylan but were significantly less active than the native enzyme against oligosaccharides smaller than xyloseptaose. These data suggest that the primary role of the F subsite of XYLA is to prevent small oligosaccharides from forming nonproductive enzyme-substrate complexes.

Amino Acid Sequence↗
PubMed1997

A survey of knowledge and use of folic acid among women of child-bearing age in Dublin.

BACKGROUND: The Medical Research Council vitamin trial highlighted the importance of folic acid in the prevention of neural tube defects. Since 1993, the Irish Department of Health has recommended periconceptional folic acid supplements. The objective of this study was to document the knowledge and behaviour of women in child-bearing years to periconceptional folic acid. METHODS: A cross-sectional community-based survey was conducted in Dublin using an interviewer administered questionnaire. RESULTS: A total of 335 women took part in the study, a response rate of 84 per cent. Approximately two-thirds (213/ 335, 63.6 per cent) had heard of folic acid. Knowledge was significantly associated with higher social class and higher education (p < 0.05). Few (18/335, 5.4 per cent), had been advised to take folic acid before pregnancy. Only 9/335 (2.7 per cent) of the women in the study were currently taking folic acid supplements. Three-quarters (75.9 per cent) of the group would be willing to take periconceptional folic acid supplements if they believed it would reduce the risk of malformations. The majority (77.4 per cent) would prefer to take folic acid in tablet form rather than have it added to food. CONCLUSIONS: This study shows that few women in child-bearing years in Dublin have been advised on folic acid, and very few are taking supplements. However, if advised appropriately the majority would be willing to take periconceptional folic acid in tablet form.

Adolescent↗
PubMed1996

Mannanase A from Pseudomonas fluorescens ssp. cellulosa is a retaining glycosyl hydrolase in which E212 and E320 are the putative catalytic residues.

Mannanase A (MANA) from Pseudomonas fluorescens, a member of glycosyl hydrolase family 26, was hyperexpressed in Escherichia coli and purified to homogeneity. Analysis of the stereochemical course of mannotetraose hydrolysis by purified MANA showed that the configuration of the anomeric carbon was retained on cleavage of the middle glycosidic bond. These data suggest that the mannanase hydrolyzes mannooligosaccharides by a double-displacement general acid-base mechanism. By hydrophobic cluster analysis (HCA), two glutamate and two aspartate residues were shown to be conserved in all of the glycosyl hydrolase family 26 enzymes analyzed. In addition, HCA suggested that family 26 was related to the GH-A clan (families 1, 2, 5, 10, 30, 35, 39, and 42) of (alpha/beta)8-barrel glycosyl hydrolases, which led to the prediction that E320 and E212 constitute the catalytic nucleophile and acid-base residues, respectively. To investigate the role of these amino acids, site-directed mutagenesis was used to replace the two aspartates with alanine and glutamate, while the two conserved glutamates were changed to alanine and aspartate. The mutant enzymes were purified and their biochemical properties were analyzed. The data showed that neither the D-->A nor the D-->E mutation resulted in a dramatic decrease in enzyme activity, suggesting that the two aspartate residues did not play a pivotal role in catalysis. In contrast, modification of either of the glutamate residues to alanine caused a dramatic decrease in kcat against carob galactomannan, azo-carob galactomannan, mannotetraose and 2,4-dinitrophenyl beta-mannobioside (2,4-DNPM). The E320A mutation did not alter the apparent K(m) (K(m)) of MANA against these substrates, while E212A resulted in a 27-fold decrease in K(m) against 2,4-DNPM. Pre-steady-state kinetics of 2,4-DNPM hydrolysis by E212A showed that there was a rapid burst of 2,4-dinitrophenol release. Circular dichroism and fluorescence spectroscopy indicated that there were no significant differences between the structures of the mutant and wild-type forms of MANA. These data are consistent with E212 and E320 constituting the catalytic acid-base and nucleophile residues of MANA, respectively.

Amino Acid Sequence↗
PubMed1995

Reversal of parkinsonian symptoms by intrastriatal and systemic manipulations of excitatory amino acid and dopamine transmission in the bilateral 6-OHDA lesioned marmoset.

We have investigated the potential of alleviating parkinsonian symptoms by manipulating excitatory amino acid (EAA) transmission, by several different pharmacological means, in a novel primate model of parkinsonism. The model is based on a two-stage bilateral 6-hydroxydopamine lesion procedure in marmosets, which produces a stable but marked parkinsonian condition. Parkinsonian symptoms were reversed in a dose-dependent manner by systemic administration of levodopa and intrastriatal injections of apomorphine administered into either the caudate nucleus or the putamen. (R)-HA-966, a partial agonist for the NMDA receptor associated glycine site, also alleviated parkinsonian symptoms when injected intrastriatally but not when injected systemically. Systemic injection of enadoline, a kappa opiate which blocks release of EAAs, reduced parkinsonian symptoms when injected systemically, though it did not restore completely normal motor behaviour. In contrast, ifenprodil, an antagonist for the NMDA receptor-associated polyamine modulatory site, when injected systemically at an optimal dose, resulted in apparently normal motor behaviour. These data suggest that attenuation of EAA transmission could be used to treat parkinsonism.

Journal Article↗
PubMed1994

Pre-emptive use of the space blanket reduces shivering after general anaesthesia.

We have investigated the role of aluminized metal foil (space blanket, UN 320), used pre-emptively, in post-anaesthetic shivering and patients' subjective perception of cold after general anaesthesia of short duration. Sixty-eight ASA I and II patients undergoing orthopaedic and plastic surgery on the peripheries were allocated randomly to two groups: those in group 1 were wrapped (not less than 60% of body surface area) in the space blanket before induction of anaesthesia. In group 2 patients had standard surgical draping. In all subjects, anaesthesia was induced with fentanyl and propofol, and maintained with nitrous oxide and enflurane in oxygen, after a laryngeal mask airway was positioned. Patients were asked to grade their perception of cold on a visual analogue scale, before induction and on recovery. Skin (dorsum of hand) and core (nasopharyngeal) temperatures were recorded at 15-min intervals. Occurrence of shivering and cold scores were recorded by blinded observers. Groups were similar in age and gender; duration of anaesthesia was also similar (mean 41.6 (SEM 4.8) vs 47.5 (3.3) min, respectively). The incidences of shivering were 15% and 63% in groups 1 and 2, respectively (P < 0.001). Cold scores were 2.4 (0.4) and 5.7 (0.5), respectively (P < 0.001). Skin temperatures increased with increasing duration of anaesthesia in both groups but were greater at 15, 30 and 45 min in group 1 (33.38 (0.25) vs 31.56 (0.31), 34.46 (0.25) vs 32.45 (0.31) and 35.22 (0.36) vs 33.13 (0.34), respectively; P < 0.001 each comparison). Core temperature increased slightly in group 1 and decreased in group 2 (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Posterior column sensory impairment during ambulatory extradural analgesia in labour.

Ambulatory or "walking" extradural analgesia in labour has recently gained popularity because of preservation of motor function and subjective somatic sensation in the lower limbs, resulting in increased maternal satisfaction. This is produced by combining dilute concentrations (e.g. 0.1%) of bupivacaine with opioids. Detailed clinical neurological examination after mobile extradural analgesia has not been reported. We have investigated the effect of 0.1% bupivacaine 15 ml and fentanyl 2 micrograms ml-1 on motor and sensory function in the lower limbs in 50 primigravidae requesting extradural analgesia in labour. This was performed before and 30 min after confirming placement of a lumbar extradural catheter. While power, co-ordination and reflexes in all lower limb muscle groups remained within normal limits, 66% (n = 33) developed abnormal distal proprioception, 44% (n = 22) had a positive Romberg's sign and 38% (n = 19) had altered vibration sense. Moreover, 44% (n = 22) said that their legs felt different on standing and they did not feel confident walking unaccompanied. However, this subjective perception correlated poorly with the presence of posterior column sensory signs. Although there was a reduction in pain scores on a visual analogue scale after 30 min (mean 8.85 (SEM 0.3) vs 3.06 (0.32); P < 0.0001), pain increased within 60 min (5.77 (0.45); P < 0.001).

Analgesia, Epidural↗
PubMed1994

A comparison of conventional SEM techniques, low temperature SEM and the electroscan wet scanning electron microscope to study the structure of a biofilm of Streptococcus crista CR3.

Biofilms of Streptococcus crista CR3 were generated on hydroxyapatite (HA) discs for 20 h in a continuous flow system with brain heart infusion broth dripped over the disc at a rate of 6 ml h-1. This study compares the conventional scanning electron microscope (SEM) preparation techniques, of critical point drying and freeze-drying, with low temperature SEM (LTSEM) and Electroscan generated images of hydrated biofilms, which preserve the integrity of hydrated polymers. Critical point drying and freeze-drying caused almost complete disappearance of the matrix of extracellular polymeric substances (EPS). Critical point drying, however, showed evenly spaced single or paired cocci remaining on the HA disc whereas freeze-drying caused the biofilm to detach from the HA leaving only patchy clumps of cells visible. By comparison LTSEM preserved the EPS better than critical point drying and freeze-drying, but holes were seen in the top and side of the biofilm and the EPS did show some shrinkage artefacts. An untreated wet biofilm viewed in the Electroscan showed an intact, hydrated, smooth matrix of EPS with cell shapes only visible indistinctly in a canopy of moist EPS. No holes were visible and no shrinkage artefacts were evident. Therefore, Electroscan imaging of the biofilm was the only method that preserved the integrity of the matrix with no apparent shrinkage artefacts.

Histocytological Preparation Techniques↗
PubMed1994

Rectal epithelial cell proliferation: comparison of errors of measurement with inter-subject variance. Australian Polyp Prevention Project Investigators.

If measures of rectal epithelial kinetics are to be used on a large scale, or as part of multicenter studies, the variance of repeated measures must be sufficiently small to detect the effect of clinical status and dietary, or chemoprevention interventions. Errors in measurement can be categorized as intra-reader (sigma 2I), inter-biopsy (sigma 2B), inter-laboratory (sigma 2L), and inter-reader (sigma 2R); the sum of these (sigma 2T) when compared to inter-subject variance (sigma 2S) is a measure of the precision with which cell kinetics can be estimated for a given subject. We estimated the variances of the component errors in four separate experiments, each involving 6 to 10 subjects, using the proliferating cell nuclear antigen (PCNA) technique. PCNA labeling index variances for a single laboratory study were sigma 2I = 0.02-0.07 and sigma 2B = 0.08-0.15. Inter-laboratory and inter-reader variances were sigma 2L = 0.08 and sigma 2R = 0.03. Summing the errors applicable within a laboratory gives a rounded estimate of 0.15. For inter-laboratory studies the total error (sigma 2T) is greater, estimated in our two-laboratory study as 0.3. In a separate study, the variation between biopsies (sigma 2B) could be accounted for by the variation between crypts within biopsies; an acceptable level of accuracy is achieved after counting 20-30 crypts. In contrast to the measurement errors, the variance between subjects, which includes a treatment effect of diet, was larger, estimated to be between 0.75 and 1.30.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗