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Biomedical subjects

R Montgomery

Publications and source records attributed to R Montgomery.

At least 19 recordsLinked to original sources

Quantitative detection of promoter hypermethylation as a biomarker of acute kidney injury during transplantation.

Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a promising biomarker approach to diagnose malignancies. Kidney repair after injury is a recapitulation of normal morphogenesis, with similarities to malignant transformation. We hypothesized that changes in urine epigenetics could be a biomarker approach during early kidney transplant injury and repair. We examined urine DNA for aberrant methylation of two gene promoters (DAPK and CALCA) by quantitative methylation-specific polymerase chain reaction from 13 deceased and 10 living donor kidney transplant recipients on postoperative day 2 and 65 healthy controls. Results were compared with clinical outcomes and to results of the kidney biopsy. Transplant recipients were significantly more likely to have aberrant hypermethylation of the CALCA gene promoter in urine than healthy controls (100% vs 31%; P < .0001). There was increased CALCA hypermethylation in the urine of deceased versus living donor transplants (21.60 +/- 12.5 vs 12.19 +/- 4.7; P = .04). Furthermore, there was a trend toward increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis versus acute rejection and slow or prompt graft function (mean: 20.40 +/- 6.9, 13.87 +/- 6.49, 17.17 +/- 13.4; P = .67). However, there was no difference of CALCA hypermethylation in urine of patients with delayed graft function versus those with slow or prompt graft function (16.9 +/- 6.2 vs 18.5 +/- 13.7, respectively; P = .5). There was no aberrant hypermethylation of DAPK in the urine of transplant patients. Urine epigenetics is a promising biomarker approach for acute ischemic injury in transplantation that merits future study.

Adult↗

Management of complex tibial and femoral nonunion using the Ilizarov technique, and its cost implications.

We reviewed 78 femoral and tibial nonunions treated between January 1992 and December 2003. Of these, we classified 41 in 40 patients as complex cases because of infection (22), bone loss (6) or failed previous surgery (13). The complex cases were all treated with Ilizarov frames. At a mean time of 14.1 months (4 to 38), 39 had healed successfully. Using the Association for the Study and Application of the Methods of Ilizarov scoring system we obtained 17 excellent, 14 good, four fair and six poor bone results. The functional results were excellent in 14 patients, good in 14, fair in two and poor in two. A total of six patients were lost to follow-up and two had amputations so were not evaluated for final functional assessment. All but two patients were very satisfied with the results. The average cost of treatment to the treating hospital was approximately pound 30,000 per patient. We suggest that early referral to a tertiary centre could reduce the morbidity and prolonged time off work for these patients. The results justify the expense, but the National Health Service needs to make financial provision for the reconstruction of this type of complex nonunion.

Adolescent↗

Postnatal changes in maternal and neonatal plasma antioxidant vitamins and the influence of smoking.

OBJECTIVE: To study the postnatal changes in the plasma concentrations of fat soluble antioxidant vitamins and malondialdehyde (MDA) in mothers and their newborns and their relation to smoking. DESIGN: Prospective cohort study. SETTING: Tertiary perinatal centre. SUBJECTS: Eighteen non-smoking and 14 smoking mothers and 33 infants. MAIN OUTCOME MEASURES: Plasma concentrations of vitamins E, A, and beta-carotene and MDA were measured in mothers and infants at delivery and on day 4 post partum. RESULTS: Neonatal plasma levels of vitamins E, A, and beta-carotene were significantly lower than maternal levels both at delivery and on day 4 in both groups. There was a significant postnatal increase in plasma vitamin E levels in smoking mothers and neonates of both groups. A significant postnatal increase in maternal, but not neonatal, plasma vitamin A was noted in both groups. Cord plasma vitamin E levels were significantly lower in infants of smoking mothers (mean 4.7 v 6.5 micromol/l, p = 0.041). Plasma MDA was paradoxically lower in smoking mothers at delivery (3.19 v 4.01 micromol/l, p = 0.03) and on day 4 (1.37 v 3.29 micromol/l, p = 0.005) and in infants of the smoking group on day 4 (2.18 v 3.12 micromol/l, p = 0.014). Also, there was a significant postnatal fall in plasma MDA levels on day 4 in mothers and infants in the smoking group. CONCLUSIONS: The postnatal changes in plasma vitamin E were more pronounced in the smoking group. The postnatal changes in plasma vitamins A and beta-carotene were similar in both groups. The rapid decline in plasma MDA in smoking mothers and their infants suggests withdrawal of oxidative stress from smoking around delivery. This coincided with the increase in plasma vitamin E.

Adolescent↗

Extracellular polysaccharides of modified strains of Erwinia spp.

The structure of the extracellular polysaccharide (EPS) produced by Erwinia chrysanthemi strain A2148 has been determined using low pressure size-exclusion and anion-exchange chromatographies, high pH anion-exchange chromatography, glycosyl-linkage analysis, and 1D 1H NMR spectroscopy. The polysaccharide is structurally similar, if not identical, to the EPS produced by E. chrysanthemi strain A350. A streptomycin-resistant strain of E. chrysanthemi Ech6 (Ech6S(+)) has been generated and has an elevated production of EPS, as does a streptomycin-resistant strain (Ech9Sm6) of E. chrysanthemi Ech9. These modified E. chrysanthemi spp. have been ribotyped and found to be closely related to their parent strains.

Carbohydrate Sequence↗

beta-Elimination of glucosyluronic residues during methylation of an acidic polysaccharide from Erwinia chrysanthemi CU 643.

The Erwinia chrysanthemi CU643 EPS has a linear hexasaccharide repeating unit in which a 4-linked uronic acid residue is present. The EPS was methylated by either the NaOH-Me2SO-MeI or Li-dimsyl procedure. MALDI-TOF MS analysis of the methylated products indicates that the beta-eliminative degradation occurs during the methylation, as characterized by serial fragments of the hexasaccharide repeating units. The degradation was clearly defined from the methylation of a glucosyluronic-containing pyruvated pentasaccharide.

Dickeya chrysanthemi↗

Pyruvated galactose and oligosaccharides from Erwinia chrysanthemi Ech6 extracellular polysaccharide.

The acidic extracellular polysaccharide of Ech6 was depolymerized by fuming HCl. The pyruvated sugars were isolated and characterized by methods that included a combination of low-pressure gel-filtration and high-pH anion-exchange chromatographies, methylation linkage analyses, mass (GC-MS and MALDI-TOF MS) and 1H NMR (1D and 2D) spectroscopies. The following pyruvated sugars were obtained: 4,6-O-(1-carboxyethylidene)-D-Galp; 4,6-O-(1-carboxyethylidene)- alpha-D-Galp-(1-->4)-beta-D-GlcAp-(1-->3)-D-Galp; 4,6-O-(1-carboxyethylidene)-alpha-D-Galp-(1-->4)-alpha-D-GlcAp- (1-->3)-alpha-D-Galp-(1-->3)-L-Fucp; 4,6-O-(1-carboxyethylidene)-alpha-D-Galp-(1-->4)-beta-D-GlcAp-(1-->3) -alpha-D-Galp-(1-->3)-L-[beta-D-Glcp-(1-->4)]-Fucp. These oligosaccharides present potential haptenes for the development of specific antibodies and confirm the partial structure proposed previously for the extracellular polysaccharide from Erwinia chrysanthemi Ech6 [Yang, B. Y.; Gray, J. S. S.; Montgomery, R. Int. J. Biol. Macromol., 1994, 16, 306-312].

Carbohydrate Conformation↗

Paediatric pelvic imaging: optimisation of dose and technique using digital grid-controlled pulsed fluoroscopy.

BACKGROUND: An audit of paediatric pelvic radiographs identified deficiencies in gonad shield placement and radiographic technique. OBJECTIVE: A technique using grid-controlled fluoroscopy (GCF), with hard copy images in frame grab and digital spot image (DSI) format was evaluated to optimise gonad shield placement and reduce the dose given to children with Perthes disease and Developmental Hip Dysplasia (DDH) attending for pelvic radiography. MATERIALS AND METHODS: Phantom and patient dose surveys of conventional and fluoroscopic techniques were carried out. Image quality and radiation dose were compared for the frame grab and DSI techniques. Retrospective evaluation was undertaken to compare their clinical acceptability. RESULTS: Both fluoroscopic techniques gave considerably less radiation than conventional non-grid radiography (67-83%, P < 0.05). The frame grab technique gave less radiation than DSI (P < 0.05). There was no significant difference in the clinical acceptability scores of the DSI and frame grab images. CONCLUSION: Fluoroscopy acquired images are now used since the fluoroscopic techniques give much less dose than conventional radiography and provide images of sufficient quality for clinical assessment. Indeed, as there was no significant difference in clinical usefulness between the frame grab and DSI techniques, it is planned to use frame grab alone, thus gaining additional dose saving.

Adolescent↗

New aspects in the pathogenesis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

The thrombotic microangiopathy (TM) syndromes, thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, are a rare and heterogeneous group of disorders characterized by widespread microvascular thrombosis and end organ injury. Decades of descriptive studies have defined clinical subsets of TM syndromes by clinical and laboratory features. Despite many advances, however, progress towards understanding of the etiology and pathogenesis of TM disorders remains limited. The rarity of occurrence and lack of natural animal models of TM syndromes have hampered progress in experimental and clinical studies. Treatment remains essentially empirical and options are limited. However, recent advances in the genetic and molecular understanding of subsets of TM disorders and the development of relevant animal models offer new resources to explore the pathogenic mechanisms. With these new advances more effective and individualized treatments for TM syndromes can be developed.

Animals↗

Extracellular polysaccharide of Erwinia chrysanthemi A350 and ribotyping of Erwinia chrysanthemi spp.

Erwinia chrysanthemi spp. are gram-negative bacterial phytopathogens causing soft rots in a number of plants. The structure of the extracellular polysaccharide (EPS) produced by the E. chrysanthemi strain A350, which is a lacZ- mutant of the wild type strain 3937, pathogenic to Saintpaulia, has been determined using a combination of chemical and physical techniques including methylation analysis, low-pressure gel-filtration and anion-exchange chromatography, high-pH anion-exchange chromatography, partial acid hydrolysis, mass spectrometry and 1- and 2D NMR spectroscopy. In contrast to the structures of the EPS reported for other strains of E. chrysanthemi, the EPS from strain A350 contains D-GalA, together with L-Rhap and D-Galp in a 1:4:1 ratio. Evidence is presented for the following hexasaccharide repeat unit: [structure: see text] All the Erwinia chrysanthemi spp. studied to date have been analyzed by ribotyping and collated into families, which are consistent with the related structures of their EPS.

Carbohydrate Conformation↗

Degree of acetylation of heteropolysaccharides.

The acetyl groups in polysaccharides and glycoproteins have been determined using 4 N HCl at 120 degrees C for acid hydrolysis. Acetic acid and hexosamine were determined by high-performance cation-exchange chromatography with UV detection and high-performance anion-exchange chromatography with pulsed amperomeric detection, respectively. The method compares well with other procedures and shows an additional advantage of being able to analyze for hexosamine in the same hydrolyzate, thus permitting the degree of acetylation of hexosamine-containing biopolymers to be determined directly without correction for additional components in the material of interest.

Acetates↗

Specialized dementia programs in residential care settings.

The authors conducted a telephone survey in 7 states to determine the prevalence of residential care specialized dementia programs (RC-SDPs) and to identify a sample of homes (n = 56) for more detailed study. The 56 homes were site visited, and data were gathered on facility administration, therapeutic environment, and characteristics of 259 randomly selected residents. Comparison data from 138 nursing home Special Care Units (NH-SCUs) and 1,340 of their residents were obtained from 4 studies conducted in the same 7 states. RC-SDPs were smaller, provided a more homelike environment, and had a higher proportion of residents paying privately, compared with NH-SCUs. Mean levels of cognitive and physical impairment among residents were higher in NH-SCUs; prevalences of psychotropic medication use and problem behaviors were similar. Among RC facilities, small homes were more homelike, provided fewer structured activities, and charged less than larger facilities. RC-SDPs include 5 types: small, independently operated homes; multiple small homes with joint administration; larger, all-dementia facilities; SDPs operated within larger, exclusively RC facilities; and RC-SDPs in multilevel facilities.

Aged↗

Autohydrolysis of phytic acid.

The autohydrolysis of phytic acid at 120 degrees C resulted in the formation of most of the phosphate esters of myo-inositol in varying amounts depending upon the reaction time. Eighteen of the 39 chromatographically distinct myo-inositol mono-, bis-, tris-, tetrakis-, pentakis-, and hexakisphosphates have been characterized using two different HPLC systems. These myo-inositol phosphates were partially purified by preparative anion-exchange chromatography under acidic and alkaline elution conditions. The combination of these two methods provides a two-tiered chromatographic approach to the rapid and sensitive identification of inositol phosphates in complex mixtures. Identification of the products was confirmed by 1D and 2D (1)H NMR analysis. The analytical procedure was applied to the autohydrolysis of the mixture of inositol phosphates from corn steep water.

Chromatography, High Pressure Liquid↗

Extracellular polysaccharide of Erwinia chrysanthemi CU643.

Erwinia chrysanthemi are gram-negative bacterial phytopathogens causing soft rots in a number of plants. The structure of the extracellular polysaccharide (EPS) produced by E. chrysanthemi strain CU643, pathogenic to Philodendron, has been determined using a combination of chemical and physical techniques including methylation analysis, high- and low-pressure gel-filtration and anion-exchange chromatography, high-pH anion-exchange chromatography, partial acid hydrolysis, mass spectrometry, and 1- and 2-D NMR spectroscopy. In contrast to the structures of the EPS reported for other strains of E. chrysanthemi, the EPS from strain CU643 is a linear polysaccharide containing L-Rhap, D-Galp, and D-GlcAp in the ratio 4:1:1. Evidence is presented for the following hexasaccharide repeat unit: -->3)-beta-D-Galp-(1-->2)-alpha-L-Rhap-(1-->4)-beta-D-GlcAp- (1-->2)-alpha-L- Rhap-(1-->2)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->(1 ).

Carbohydrate Sequence↗

Intravenous ondansetron for the control of opioid-induced nausea and vomiting. International S3AA3013 Study Group.

This randomized, double-masked, placebo-controlled, multicenter trial was conducted in 9 countries to assess the safety and efficacy of 2 doses of intravenous ondansetron (8 and 16 mg) for the control of opioid-induced nausea and vomiting. A total of 2574 nonsurgical patients who presented with pain requiring treatment with an opioid analgesic agent participated in this trial. The most common presenting painful condition was back or neck pain, reported by approximately one third of patients. A total of 520 patients (317 females, 203 males) developed nausea or vomiting after opioid administration and were randomly assigned to receive a single dose of 1 of 3 study treatments: placebo (n = 94), ondansetron 8 mg (n = 215), or ondansetron 16 mg (n = 211). Ondansetron 8 and 16 mg led to complete control of emesis in 134 of 215 patients (62.3%) and 145 of 211 patients (68.7%), respectively. Results with both doses were significantly better than those seen with placebo (43 of 94 patients [45.7%]). Complete control of nausea was achieved in 6.8% of placebo patients, 14.8% of ondansetron 8-mg-treated patients, and 19.4% of ondansetron 16-mg treated patients; only ondansetron 16 mg was significantly better than placebo (P = 0.007). Significantly more patients who received ondansetron 8 mg than patients who received placebo were satisfied/very satisfied with their antiemetic treatment, as assessed by 4 patient-satisfaction questions. Significantly more patients who received ondansetron 16 mg compared with placebo were satisfied/very satisfied on 2 of 4 satisfaction questions. In conclusion, based on the observed incidence of opioid-induced nausea and vomiting in this study, it may be more appropriate to treat symptoms on occurrence rather than administering antiemetic agents prophylactically. The results of this study demonstrate that intravenous ondansetron in doses of 8 or 16 mg is an effective antiemetic agent for the control of opioid-induced nausea and vomiting in nonsurgical patients requiring opioid analgesia for pain.

Adult↗

Heterogeneity of glycans at each N-glycosylation site of horseradish peroxidase.

The tryptic glycopeptides of horseradish peroxidase isozyme c (HRPc) were studied by methylation linkage analysis, exoglycosidase degradation, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOFMS). Over 90% of the predicted tryptic peptides and glycopeptides of HRPc could be identified in the unfractionated digest. Four glycans, namely (Xyl)Man3(Fuc)GlcNAc2 (major species), (Xyl)Man2(Fuc)GlcNAc2, (Xyl)Man3GlcNAc2, and Man3(Fuc)GlcNAc2 (minor species), were observed at all of the N-glycosylation sites and account for greater than 95% of the carbohydrate. Other members of this glycan family, namely (Xyl)xManm(Fuc)f GlcNAc2 (x = 0 or 1, f = 0 or 1, m = 4, 5, 6, or 7), account for the rest of the glycans. Only traces of high mannose-type glycans were detected in HRPc. Two sites, namely those at Asn-57 and Asn-267, were found to be more heterogeneous than the sites at Asn-13, Asn-158, Asn-186, 198 (doubly glycosylated peptide), Asn-214, and Asn-255. Two of the glycopeptides were observed as part of disulfide-linked species. MALDITOFMS confirmed the N-glycosylation sites previously reported [K.G. Welinder, Eur. J. Biochem., 96 (1979) 483-502] and was used to determine the heterogeneity of the glycan pool at each site.

Amino Acid Sequence↗