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Biomedical subjects

S Elliott

Publications and source records attributed to S Elliott.

At least 19 recordsLinked to original sources
PubMed1998

Cardiovascular changes during laparoscopic cholecystectomy: a study using transoesophageal Doppler monitoring.

A transoesophageal Doppler cardiac output monitor was used to study the cardiovascular changes occurring during laparoscopic cholecystectomy in patients without (group A) or with (group B) a history of cardiovascular disease, i.e. hypertension, ischaemic heart disease or heart failure. Insufflation of the abdomen with carbon dioxide caused significant (P < 0.01) falls in mean cardiac index (17.9% in group A, 25.1% in group B) and mean stroke volume index (15.3% in group A, 21.2% in group B). Simultaneously, there was a significant (P < 0.05) increase in mean systolic blood pressure (19.4%) in group A. There were no other differences in the cardiovascular responses of the two groups. There was no correlation between systolic blood pressure and either cardiac index or stroke volume index. No significant complications or morbidity were associated with the use of the transoesophageal Doppler monitor. We conclude that the cardiovascular changes associated with insufflation are neither predictable by clinical assessment nor adequately determined by routine monitoring. We recommend the transoesophageal Doppler monitor for use in this situation.

Blood Pressure↗
PubMed1998

Molecular evolution of a pathogenicity island from enterohemorrhagic Escherichia coli O157:H7.

We report the complete 43,359-bp sequence of the locus of enterocyte effacement (LEE) from EDL933, an enterohemorrhagic Escherichia coli O157:H7 serovar originally isolated from contaminated hamburger implicated in an outbreak of hemorrhagic colitis. The locus was isolated from the EDL933 chromosome with a homologous-recombination-driven targeting vector. Recent completion of the LEE sequence from enteropathogenic E. coli (EPEC) E2348/69 afforded the opportunity for a comparative analysis of the entire pathogenicity island. We have identified a total of 54 open reading frames in the EDL933 LEE. Of these, 13 fall within a putative P4 family prophage designated 933L. The prophage is not present in E2348/69 but is found in a closely related EPEC O55:H7 serovar and other O157:H7 isolates. The remaining 41 genes are shared by the two complete LEEs, and we describe the nature and extent of variation among the two strains for each gene. The rate of divergence is heterogeneous along the locus. Most genes show greater than 95% identity between the two strains, but other genes vary more than expected for clonal divergence among E. coli strains. Several of these highly divergent genes encode proteins that are known to be involved in interactions with the host cell. This pattern suggests recombinational divergence coupled with natural selection and has implications for our understanding of the interaction of both pathogens with their host, for the emergence of O157:H7, and for the evolutionary history of pathogens in general.

Amino Acid Sequence↗
PubMed1998

Influence of port site on central venous pressure measurements from triple-lumen catheters in critically ill adults.

BACKGROUND: Measurements of central venous pressure are generally obtained through one of the three ports of centrally placed triple-lumen catheters. However, no scientifically based literature is available that guides clinical practice and indicates which of the lumens is most appropriate for obtaining these measurements. OBJECTIVE: To determine if a difference exists between measurements of central venous pressure obtained via the proximal, medial, and distal ports of a triple-lumen catheter. METHODS: Measurements of central venous pressure in 48 adult ICU patients were obtained via each of the three ports of a triple-lumen catheter. Catheters were placed in either the right or left subclavian vein or the right or left internal jugular vein. The flush system was single-transducer, trifurcated pressure tubing system. Data were evaluated for variation among the three ports of the catheter for readings taken at a single point. RESULTS: A repeated-measures analysis of variance showed significant differences across port sites. Post hoc univariate F tests showed significant differences between the proximal and distal ports and between the medial and distal ports. In some patients, the difference between central venous pressure obtained from the distal port and pressure obtained from the proximal or the medial port may be clinically significant. CONCLUSION: Because measurements of central venous pressure may not always be comparable for all three ports of a triple-lumen catheter, care should be taken to distinguish when changes in pressure readings are a result of a change in port site rather than in the patient's condition.

Adult↗
PubMed1997

Mapping of the active site of recombinant human erythropoietin.

Recombinant human erythropoietin (rHuEPO) variants have been constructed to identify amino acid residues important for biological activity. Immunoassays were used to determine the effect of each mutation on rHuEPO folding. With this strategy, we could distinguish between mutations that affected bioactivity directly and those that affected bioactivity because the mutation altered rHuEPO conformation. Four regions were found to be important for bioactivity: amino acids 11 to 15, 44 to 51, 100 to 108, and 147 to 151. EPO variants could be divided into two groups according to the differential effects on EPO receptor binding activity and in vitro biologic activity. This suggests that rHuEPO has two separate receptor binding sites. Mutations in basic residues reduced the biologic activity, whereas mutations in acidic residues did not. This suggests that electrostatic interactions between rHuEPO and the human EPO receptor may involve positive charges on rHuEPO.

Amino Acid Sequence↗
PubMed1997

Does the addition of clonidine affect duration of analgesia of bupivacaine wound infiltration in inguinal hernia surgery?

We conducted a prospective, randomized, double-blind study to compare analgesia obtained by wound infiltration using 29 ml of 0.25% bupivacaine alone, or with the addition of clonidine hydrochloride 150 micrograms. A third group received bupivacaine wound infiltration with clonidine 150 micrograms i.m. to control for the systemic effects caused by absorption of clonidine. We studied 46 adults undergoing elective inguinal hernia repair. The general anaesthetic technique, postoperative analgesia and wound infiltration technique were standardized. There was no difference in time to first analgesic request or to total analgesic consumption between the three groups during the 24-h study. Visual analogue scores (VAS) at rest and after coughing were noted over a 24-h period. The only difference was higher VAS scores at rest at 24 h in the control group who received i.m. clonidine. We conclude that for elective inguinal hernia repair, postoperative analgesia obtained by bupivacaine wound infiltration was not improved by the addition of clonidine 150 micrograms.

Adrenergic alpha-Agonists↗
PubMed1997

Cellulitis and myositis caused by Agrobacterium radiobacter and Haemophilus parainfluenzae after influenza virus vaccination.

Agrobacterium radiobacter is a gram-negative aerobic bacillus that has been reported as a cause of disease only 36 times in the literature. More than half of the patients (25) have had bacteremia. Peritonitis, urinary tract infection, endocarditis, and one case of cellulitis associated with bacteremia have also been reported. Infection is often associated with immunosuppression and the presence of a plastic foreign body, such as central venous catheters, nephrostomy tubes, intraperitoneal catheters, and prosthetic cardiac valves. We present apparently the first case of A radiobacter causing myositis after influenza virus vaccination.

Adult↗
PubMed1997

The Belfast Cord Blood Bank.

The first cord blood bank in the British Isles was established in Belfast in June 1993. Cord blood (CB) is rich in haematopoietic progenitor cells and has been used successfully as a substitute for bone marrow transplants in over 200 patients world-wide. Most have received CB from a histocompatible sibling, but reports include several unrelated HLA matched transplants. In addition to the cryopreservation of 400 units of donated CB in the Cord Blood Bank, we have stored eight CB collections from siblings of children with leukaemia in Northern Ireland. A pilot study in collaboration with the maternity unit in the Mater Infirmorum Hospital confirmed the feasibility of a CB banking programme and highlighted many issues relating to Good Manufacturing Practice (GMP). The authors describe experience of collecting 824 units of CB over three years and discuss a few of the wider implications of this innovation in the management of patients requiring myeloablative therapy.

Adult↗
PubMed1996

Activation of the erythropoietin (EPO) receptor by bivalent anti-EPO receptor antibodies.

Oligomerization of cytokine receptors including the erythropoietin (EPO) receptor has been advanced as a model for activation. If homodimerization of the EPO receptor activates it, then bivalent antibodies raised to the extracellular domain of the EPO receptor should also homodimerize and activate. Mouse monoclonal antibodies (IgG) raised to the soluble, extracellular domain of the human EPO receptor (EPOR) were found that would stimulate thymidine uptake of an human EPO-dependent cell line, UT-7/EPO. Dose response curves showed bell shapes where activity was low at low and high concentrations. Monovalent (Fab) fragments bound to the receptor but did not stimulate thymidine uptake, which indicates that two antibody binding sites are required for activation. The anti-EPOR antibodies stimulated the formation of burst forming unit erythroid colonies from human CD34(+) cells purified from peripheral blood. This indicates that homodimerization of the EPO receptor by anti-EPOR antibodies is sufficient for both proliferation and differentiation of erythroid progenitor cells and that the constraints on dimerization necessary for activation are rather loose.

Animals↗
PubMed1996

Fine-structure epitope mapping of antierythropoietin monoclonal antibodies reveals a model of recombinant human erythropoietin structure.

We have isolated and mapped the rHuEPO epitopes for three noncompeting anti-EPO monoclonal antibodies (MoAbs). The MoAb 9G8A recognizes a linear epitope that includes amino acids 13, 16, and 17. MoAb F12 recognizes a conformational epitope that includes amino acids 31 through 33, 86 through 91, and 138. MoAb D11 recognizes a conformational epitope that includes amino acids 64 through 78 and 99 through 110. MoAb D11 neutralizes rHuEPO activity which suggests that its epitope may contain the receptor binding domain. Analysis of the effect of mutations on folding allowed the identification of buried residues, alpha-helical, and non alpha-helical regions. This data along with epitope mapping data of anti rHuEPO monoclonals was used to model rHuEPO protein structure. A model consistent with the data is a 4-helix bundle with short and long interconnecting loops.

Amino Acid Sequence↗
PubMed1996

Isolation and characterization of conformation sensitive antierythropoietin monoclonal antibodies: effect of disulfide bonds and carbohydrate on recombinant human erythropoietin structure.

We have isolated and characterized three anti-recombinant human erythropoietin (rHuEPO) monoclonal antibodies (MoAbs) that recognize nonoverlapping epitopes on rHuEPO. Anti-EPO MoAb D11 neutralizes rHuEPO activity whereas MoAbs F12 and 9G8A do not. This suggests that D11 may bind to the rHuEPO active site. MoAbs F12 and D11 recognize conformation dependent epitopes whereas 9G8A does not. Immunoassays were developed for each monoclonal. The 9G8A immunoassay was novel and useful because immunoreactivity increased when rHuEPO was denatured. Disruption of disulfide bonds or removal of carbohydrate increased 9G8A immunoreactivity, which suggests that these elements are important for rHuEPO structure or stability.

Antibodies, Monoclonal↗
PubMed1996

Isolation of an ovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica.

Ovine pulmonary surfactant is bactericidal for Pasteurella haemolytica when surfactant and bacteria mixtures are incubated with normal ovine serum. To isolate this component, surfactant (1 mg/ml) was centrifuged at 100,000 x gav, and the supernatant was fractionated by HPLC. Fractions were eluted with acetonitrile (10-100%)/0.1% trifluoracetic acid and tested for bactericidal activity. Amino acid and sequence analysis of three bactericidal fractions showed that fraction 2 contained H-GDDDDDD-OH, fraction 3 contained H-DDDDDDD-OH, and fraction 6 contained H-GADDDDD-OH. Peptides in 0.14 M NaCl/10 microM ZnCl2 (zinc saline solution) induced killing of P. haemolytica and other bacteria comparable to defensins and beta-defensins [minimal bactericidal concentration (MBC)50 range, 0.01-0.06 mM] but not in 0.14 M NaCl/10 mM sodium phosphate buffer, pH 7.2/0.5 mM CaCl2/0.15 mM MgCl2 (MBC50 range, 2.8-11.5 mM). Bactericidal activity resided in the core aspartate hexapeptide homopolymeric region, and MBC50 values of aspartate dipeptide-to-heptapeptide homopolymers were inversely proportional to the number of aspartate residues in the peptide. P. haemolytica incubated with H-DDDDDD-OH in zinc saline solution was killed within 30 min. Ultrastructurally, cells contained flocculated intracellular constituents. In contrast to cationic defensins and beta-defensins, surfactant-associated anionic peptides are smaller in size, opposite in charge, and are bactericidal in zinc saline solution. They are members of another class of peptide antibiotics containing aspartate, which when present in pulmonary secretions may help clear bacteria as a part of the innate pulmonary defense system.

Amino Acid Sequence↗
PubMed1995

Atlantoaxial instability in Down's syndrome: a five year follow up study.

In 1986 all 90 children aged 4-19 years with Down's syndrome attending school in the area served by the Southern Derbyshire Health Authority underwent radiography to identify atlantoaxial instability (AAI). This study details repeat observations five years later. Full results were available on 67 (74%), information on health status was available on the remaining 19 (21%); four (4%) were untraced. There was an overall significant reduction in the atlanto-axial gap over five years. No one developed AAI on repeat testing who had not had it earlier. One child who had previously had normal neck radiography developed acute symptomatic AAI after ear, nose, and throat surgery. Radiographs were done on three occasions on the same day in 49 individuals, ensuring full flexion of the upper neck. There were no significant differences between the radiographs, even in five subjects with AAI. Management of AAI in Down's syndrome is discussed in the light of these findings. Radiography can reliably detect children with chronic AAI who may be at risk of gradually developing symptoms; this may justify a screening programme. This must be distinguished from those who develop symptoms after acute trauma or anaesthesia, for which specific precautions are needed, and previous screening radiographs are unhelpful.

Adolescent↗
PubMed1994

Structural requirements for addition of O-linked carbohydrate to recombinant erythropoietin.

To define the structural requirements for addition of O-linked glycosylation in vivo, recombinant erythropoietin (rEPO) variants were constructed. Thirty-three independent Ser or Thr substitutions were constructed and examined to see which were subject to O-linked carbohydrate addition. Variants with Thr mutations at positions 123 and 125, but not elsewhere, contained additional carbohydrate, which suggests that several positions around the existing O-linked glycosylation site (Ser126), but not elsewhere, contain the necessary information for O-linked carbohydrate addition. Two forms of the Thr125 variant were identified. One form was glycosylated only at residue 125, and a second form was glycosylated at both Thr125 and Ser126, the normal O-glycosylation site. We have also found that glycosylation is less efficient when rEPO is improperly folded and that prolines at -1 and +1 relative to the O-glycosylation site enhance glycosylation.

Amino Acid Sequence↗
PubMed1993

Small incision laser lift for forehead creases and glabellar furrows.

A new technique for eliminating or reducing glabellar frown lines and forehead creases with a small (3- to 5-cm) incision, KTP (potassium [K]-titanyl-phosphate) laser (Laserscope), and endoscope (Karl Storz) has been performed on 62 patients over the last 18 months. This endolaser technique takes advantage of the unique properties of the frequency-doubled Nd:Yag (neodymium:yttrium aluminum garnet) (KTP) laser coupled with an optimized quartz contact probe. It enables the surgeon to incise or excise the procerus, corrugator, and frontalis muscles, with little or no bleeding, at a distance from a small incision immediately behind the hairline. This small incision frontal lift has been as effective as the standard forehead lift in rejuvenation of the upper face, avoiding the paresthesias, scalp itch, headaches, periorbital ecchymosis, and hair loss that are common sequelae of the forehead lift. Recovery time has been markedly reduced.

Female↗