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Biomedical subjects

P A Evans

Publications and source records attributed to P A Evans.

At least 19 recordsLinked to original sources
PubMed2004

Paroxysmal supraventricular tachycardia: improving diagnosis and management within the accident and emergency department.

Accident and emergency (A&E) senior house offices (SHOs) have difficulties in interpreting the electrocardiogram (ECG) in narrow complex tachycardia. Correct ECG interpretation is fundamental to patient management in paroxysmal supraventricular tachycardia. This study aimed to assess the ability of A&E SHOs to interpret the ECG in this setting. Correct diagnosis in 63% of cases improved to 86% with the introduction of a standard protocol sheet. Ensuring that SHOs follow agreed guidelines in rhythm recognition and management of PSVT improves patient care.

Clinical Competence↗
PubMed2003

Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery.

A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery.

Adenosine Diphosphate↗
PubMed2003

Can the effects of clinical reperfusion fluids on platelet aggregation in vitro predict the effects of administration of such fluids in a clinical study ex vivo?

Reperfusion fluids are administered routinely during surgical operations and following trauma. Studies performed wholly in vitro have indicated effects of some fluids on haemostasis through inhibition of platelet aggregation. Recently we performed a study to further evaluate the effects of reperfusion studies in vitro and also a study in a clinical setting to determine the extent to which the results of in vitro experiments can be extrapolated to the clinical situation. The results indicate that a combination of homeostatic and trauma response mechanisms complicate the ability to extrapolate from the findings in vitro.

Hemostasis↗
PubMed2003

Scrotal pain in the absence of torsion; need for vigilance.

Epididymitis is a common presentation of acute testicular pain seen in the emergency department, the differential diagnosis being testicular torsion. The vast majority of young men with epididymitis have an infective aetiology and this settle with antibiotic treatment. The clinical course of a patient who presented with testicular pain is described. At ultrasonography, the patient was found to have the uncommon condition of testicular microlithiasis, a condition that has been linked to malignant disease. Emergency doctors should be aware of the potential consequences of returning scrotal pain consistent with epididymitis to the community on antibiotic treatment alone. All patients with probable epididymitis should have either a scrotal ultrasound or specialist follow up.

Adult↗
PubMed2002

Accidental hypothermia and active rewarming: the metabolic and inflammatory changes observed above and below 32 degrees C.

OBJECTIVES: In accidental hypothermia the underlying physiological mechanisms responsible for poor outcome during rewarming through 32 degrees C remain obscure, although possible associations include changes in acid-base balance, divalent cations, and inflammatory markers. This study investigated the metabolic and inflammatory changes that occur during the rewarming of hypothermic patients. METHODS: Eight patients, four men and four women, age 45 to 85 years, admitted with core temperatures <35 degrees C were included in the study. Patients were rewarmed with dry warm blankets and fluid replaced by crystalloid at 40 degrees C. Bloods for pH, ionised calcium (Ca(2+)) and magnesium (Mg(2+)), parathyroid hormone (PTH), interleukin 1 (IL1), interleukin 6 (IL6), tissue necrosis factor alpha (TNFalpha), were collected at presentation, during rewarming, and at 24 hours. RESULTS: Four patients were admitted with mild (32 degrees -35 degrees C) and four with moderate (28 degrees -32 degrees C) hypothermia. Rewarming to 32 degrees C had no significant effect on the presenting acidosis (p=0.1740), although above 32 degrees C pH increased with temperature (p<0.0001). There was a negative correlation between pH and both Ca(2+) (p=0.0005) and Mg(2+) (p=0.0488) below 32 degrees C; above this temperature the relation was significant only for Ca(2+) (p=0.0494). PTH and Ca(2+) correlated positively (p=0.0041) and negatively (p=0.0039) below and above 32 degrees C respectively. There was no relation between IL1 or TNFalpha with Ca(2+) during rewarming, but IL6 and Ca(2+) correlated positively (p=0.0039) and negatively (p=0.0018) when presentation temperature was below and above 32 degrees C respectively. CONCLUSIONS: During rewarming pH remains unchanged until patient temperature approaches 32 degrees C. Ca(2+) and Mg(2+) decline is associated with the pH increase above 32 degrees C. Poor outcome is associated with presentation temperature (<32 degrees C), non-physiological correlation between IL6-PTH-Ca(2+), and age (>or=84 years).

Aged↗
PubMed2001

Structure and properties of a dimeric N-terminal fragment of human ubiquitin.

Previous peptide dissection and kinetic experiments have indicated that in vitro folding of ubiquitin may proceed via transient species in which native-like structure has been acquired in the first 45 residues. A peptide fragment, UQ(1-51), encompassing residues 1 to 51 of ubiquitin was produced in order to test whether this portion has propensity for independent self-assembly. Surprisingly, the construct formed a folded symmetrical dimer that was stabilised by 0.8 M sodium sulphate at 298 K (the S state). The solution structure of the UQ(1-51) dimer was determined by multinuclear NMR spectroscopy. Each subunit of UQ(1-51) consists of an N-terminal beta-hairpin followed by an alpha-helix and a final beta-strand, with orientations similar to intact ubiquitin. The dimer is formed by the third beta-strand of one subunit interleaving between the hairpin and third strand of the other to give a six-stranded beta-sheet, with the two alpha-helices sitting on top. The helix-helix and strand portions of the dimer interface also mimic related features in the structure of ubiquitin. The structural specificity of the UQ(1-51) peptide is tuneable: as the concentration of sodium sulphate is decreased, near-native alternative conformations are populated in slow chemical exchange. Magnetization transfer experiments were performed to characterize the various species present in 0.35 M sodium sulphate, namely the S state and two minor forms. Chemical shift differences suggest that one minor form is very similar to the S state, while the other experiences a significant conformational change in the third strand. A segmental rearrangement of the third strand in one subunit of the S state would render the dimer asymmetric, accounting for most of our results. Similar small-scale transitions in proteins are often invoked to explain solvent exchange at backbone amide proton sites that have an intermediate level of protection.

Amino Acid Sequence↗
PubMed2001

Regioselective and enantiospecific rhodium-catalyzed allylic amination with N-(arylsulfonyl)anilines.

[reaction: see text]. The regioselective and enantiospecific rhodium-catalyzed allylic amination of secondary allylic carbonates 1 with N-(arylsulfonyl)anilines provides a convenient process for the construction of arylamines 2. This method, in conjunction with ring-closing metathesis and radical cyclization reactions, allows the direct construction of biologically relevant pharmacophores as exemplified by the construction of dihydroquinoline and dihydrobenzo[b]indoline derivatives.

Amination↗
PubMed2001

Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy.

Previous studies have suggested that the level of residual disease at the end of therapy predicts outcome in chronic lymphocytic leukemia (CLL). However, available methods for detecting CLL cells are either insensitive or not routinely applicable. A flow cytometric assay was developed that can differentiate CLL cells from normal B cells on the basis of their CD19/CD5/CD20/CD79b expression. The assay is rapid and can detect one CLL cell in 10(4) to 10(5) leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in nonresponders. Patients with more than 0.01 x 10(9)/L circulating CLL cells always had significant (> 5%) marrow disease, and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer Institute (NCI) criteria, the detection of residual bone marrow disease at more than 0.05% of leukocytes in 6 out of 25 patients predicted significantly poorer event-free (P =.0001) and overall survival (P =.007). CLL cells are detectable at a median of 15.8 months (range, 5.5-41.8) posttreatment in 9 out of 18 evaluable patients with less than 0.05% CLL cells at end of treatment. All patients with detectable disease have progressively increasing disease levels on follow-up. The use of sensitive techniques, such as the flow assay described here, allow accurate quantitation of disease levels and provide an accurate method for guiding therapy and predicting outcome. These results suggest that the eradication of detectable disease may lead to improved survival and should be tested in future studies.

Adult↗
PubMed2001

The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma.

Initial studies with high-dose therapy (HDT) in myeloma suggest some beneficial effects of attaining a complete response (CR); however, the effect on survival is difficult to assess owing to inconsistencies in the definition of response between studies. We have analysed 96 newly diagnosed patients aged less than 65 years who received HDT and assessed the effect of response on survival using electrophoresis, immunofixation and fluorescent IgH polymerase chain reaction (PCR) to define CR. Patients received induction chemotherapy with C-VAMP (adriamycin, vincristine, methylprednisolone, cyclophosphamide) followed by melphalan 200 mg/m2 and reinfusion of peripheral blood stem cells. There was a high response to C-VAMP [CR = 24%, partial response (PR) = 64%], with all but one patient improving the depth of response after HDT (CR = 69%, PR = 31%). The progression-free survival (PFS) and overall survival (OS) were excellent at a median of 46.4 months and 72+ months. There was a trend towards an improved PFS in patients with an immunofixation-negative CR compared with patients with a PR (49.4 months, 41.14 months; P = 0.26). This was not evident when electrophoresis was used to define CR. The method used to define CR did not impact on the overall survival and fluorescent IgH PCR failed to add any additional prognostic information. This study supports the widespread use of the European Bone Marrow Transplantation group (EBMT) response criteria and suggests that immunofixation should be performed on all patients who become electrophoresis negative.

Adult↗
PubMed2001

The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin.

It is known that the peptide corresponding to the N-terminal beta-hairpin of ubiquitin, U(1-17), can populate the monomeric beta-hairpin conformation in aqueous solution. In this study, we show that the Gly-10 that forms the bulge of the beta-turn in this hairpin is very important to the stability of the hairpin. The deletion of this residue to desG10(1-16) unfolds the structure of the peptide in water. Even under denaturing conditions, this bulge appears to be important in maintaining the residual structure of ubiquitin, which involves tertiary interactions within the sequence 1 to 34 in the denatured state. We surmise that this residual structure functions as one of the nucleation centers in the folding process and is important in stabilizing the transition state. In accordance with this idea, deleting Gly-10 slows down the refolding and unfolding rate by about one half.

Amino Acid Substitution↗
PubMed2001

Exact algorithms for computing pairwise alignments and 3-medians from structure-annotated sequences (extended abstract).

Given the problem of mutation saturation in ancient molecular sequences, there is great interest in inferring phylogenies from higher-order types of molecular data that change more slowly, such as genomic organization and the secondary and tertiary structures of ribosomal RNA and proteins. In this paper, we define edit distances based on two representations of RNA secondary structure, arc annotation and hierarchical string annotation, and give algorithms for computing these distances on pairs of annotated sequences, aligning pairs of annotated sequences, and computing 3-median annotated sequences from triples of annotated sequences. The 3-median algorithms can be used as part of a well-known iterative heuristic for inferring phylogenies. All given algorithms are adapted from algorithms for computing longest common annotated subsequences of pairs of annotated sequences.

Algorithms↗
PubMed2001

Performance assessment of the Gulmay D3300 kilovoltage X-ray therapy unit.

A performance assessment was made of the Gulmay D3300 kilovoltage (combined superficial and orthovoltage) X-ray therapy unit. Results are presented for the key dosimetric beam parameters required for routine patient treatment. This unit is relatively new to the UK market and displayed similar properties to other existing equipment. Beam half-value layers were different from comparable published data, but were consistent with the actual values of external tube filtration employed. The applicator, system interlocks and dose monitor performance were satisfactory and the tube leakage was below the UK recommended maximum (air kerma rate 300 mGy h(-1) at 5 cm from the tube head). The variation of absorbed dose with stand-off distance from the applicator base followed the inverse-square law for all tested combinations of beam tube potential (kVp) and applicator, and the measured focus-to-surface distances were in acceptable agreement with the nominal values. A significant beam profile asymmetry was seen for field sizes greater than 10 cm at the upper tube potential (kVp) range (maximum ionization quotient 1.08), but this was an inherent property of the X-ray tube. The difficulties of obtaining percentage depth dose measurements are discussed, and it was concluded that the use of published data (appropriately verified) was acceptable. The methodology followed could form the basis of an acceptance and commissioning protocol. To address the relative lack of agreed standards for this type of equipment, performance test tolerances are proposed that are recommended for new installations.

Equipment Design↗
PubMed2000

Stereoselective synthesis of cyclic ethers using vinylogous sulfonates as radical acceptors: effect of E/Z geometry and temperature on diastereoselectivity.

Treatment of the E-vinylogous sulfonates 1a-g with tris(trimethylsilyl)silane and triethylborane, in the presence of air, furnished the cyclic ethers 2/3a-g with good to excellent diastereoselectivity favoring the cis-isomer 2. This study demonstrated the level of stereocontrol in a 6-exo radical cyclization and may be attributed to the type of radical intermediate. Hence, the modest selectivity obtained for the cyclization of 1e may be a function of the acyl radical geometry (sp2) and high inversion barrier (29 kcal/mol) as compared to the alkyl (1 kcal/mol) and vinyl (2.9 kcal/mol) radicals. This is consistent with the acyl radical cyclization having an earlier transition state than the corresponding alkyl and vinyl radicals. The modest diastereoselectivity can be improved dramatically using the Z-vinylogous sulfonate (> or =34:1; R = Ph) to promote kinetic trapping of the s-trans rotamer I and III, respectively (Figure 1). The 5-exo alkyl radical cyclization reaction under nonreductive Keck-allylation conditions was also examined, in which 8 was formed in 91% overall yield. This transformation provides a convenient method for in situ homologation and should be applicable to target directed synthesis.

Cyclization↗