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K Sykes

Publications and source records attributed to K Sykes.

At least 19 recordsLinked to original sources
PubMed2004

The influence of Sir Robert Reynolds Macintosh on the development of anaesthesia.

Fifteen years ago, on the 28th of August 2004, one of the British pioneers of anaesthesiology, Sir Robert Reynolds Macintosh, died in Oxford. Since he had a major influence on the development of anaesthesia in Europe and the rest of the world, we felt it would be appropriate to review his life and work. Macintosh was the first Nuffield Professor of Anaesthetics in the University of Oxford, so we provide a brief biography of Lord Nuffield and describe the historical background to the creation of the chair. We then outline Sir Robert's early life and describe pre-war developments at Oxford, including the development of the calibrated Oxford vaporizer for ether and laryngoscope. We discuss the wartime research into survival at high altitudes, the design of life-jackets and the efficiency of methods of artificial ventilation, and then show how Sir Robert pioneered a more open approach to the problem of anaesthetic-related deaths. We list some of the anaesthesiological textbooks which were translated into German, and then describe how his overseas travels influenced the teaching of anaesthesiology all over the world. We record Sir Robert Macintosh's connections with East and West Germany and note how he encouraged the development of academic departments of anaesthesia worldwide.

Anesthesia↗
PubMed2000

Procalcitonin may help differentiate disseminated herpes simplex viral infection from bacterial sepsis in neonates.

UNLABELLED: Disseminated herpes simplex virus infection is a potentially fatal condition which may be difficult to differentiate from bacterial sepsis. We report the case of a neonate with overwhelming herpes simplex (type 2) viraemia who presented with 'septic shock'. CONCLUSION: A low procalcitonin level (1.6 ng/ml), inconsistent with bacteraemia, suggests an alternative aetiology and may strengthen the case for antiviral therapy.

Biomarkers↗
PubMed2000

Exercise training for claudicants: changes in blood flow, cardiorespiratory status, metabolic functions, blood rheology and lipid profile.

OBJECTIVE: Exercise training improves the walking distance of claudicants. The aim of this study was to investigate factors associated with the improvement in the maximum walking distance (MWD) in respect to cardiovascular, respiratory and metabolic adaptations. METHODS: Forty claudicants were studied. Common femoral artery blood flow (BF), heart rate (HR), oxygen consumption (VO(2)), respiratory exchange ratio (RER), lactate levels, blood rheology and lipid profiles were measured. Tests were repeated after 3 months of exercise training. RESULTS: Fifteen patients did not complete the exercise program. For patients who did complete the program, MWD improved by 82%. A significant reduction in HR and VO(2)during exercise was demonstrated. No significant changes occurred in BF or RER. Although MWD increased significantly, there was no increase in recovery VO(2)(oxygen debt). A significant reduction in post-exercise lactate levels occurred. Blood rheology was unchanged, but an improvement in HDL levels was noted. CONCLUSIONS: Many claudicants could not complete an exercise program, mainly due to osteoarthritis. Exercise training improved exercise tolerance significantly without any increase in BF. The HR and oxygen cost of similar exercise was reduced. An improved MWD did not correlate with a higher oxygen debt or lactate load. Favourable changes in lipid profiles occurred.

Aged↗
PubMed2000

Applications of, and future challenges for, genetic vaccines.

Genetic vaccines have progressed significantly since the first demonstration of the technology in 1992. When Sanford and Johnston first developed the idea, two applications were envisaged. One was as a new, simple, possibly more effective, method for delivering vaccines. The other was as a new tool to explore the immune system and to discover new vaccines. As there has been relatively little emphasis on the latter, we provide three examples of the potential uses of genetic immunization for discovery/manipulation. One of these technologies may have important implications for the safety of the vaccines. Finally, we propose that the clinical application of genetic vaccines may be limited by inadequate delivery systems and propose the characteristics of an ideal system.

Animals↗
PubMed1999

Guillain-Barré syndrome: delayed diagnosis following anaesthesia.

Guillain-Barré syndrome following anaesthesia or surgery is rare. Diagnosis is often delayed, which may lead to an increase in morbidity. There is now good evidence that early diagnosis and treatment reduces this morbidity. The two cases highlight the difficulties with diagnosis in the perioperative period and further discuss the aetiology, diagnostic features and complications of childhood Guillain-Barré syndrome.

Anesthesia, General↗
PubMed1999

Diagnostic markers of infection: comparison of procalcitonin with C reactive protein and leucocyte count.

BACKGROUND: Procalcitonin has been advocated as a marker of bacterial infection. OBJECTIVE: To evaluate diagnostic markers of infection in critically ill children, comparing procalcitonin with C reactive protein and leucocyte count in a paediatric intensive care unit (PICU). METHODS: Procalcitonin, C reactive protein, and leucocyte count were measured in 175 children, median age 16 months, on admission to the PICU. Patients were classified as: non-infected controls (43); viral infection (14); localised bacterial infection without shock (25); bacterial meningitis/encephalitis (10); or septic shock (77). Six children with "presumed septic shock" (without sufficient evidence of infection) were analysed separately. Optimum sensitivity, specificity, predictive values, and area under the receiver operating characteristic (ROC) curve were evaluated. RESULTS: Admission procalcitonin was significantly higher in children with septic shock (median 94.6; range 3.3-759.8 ng/ml), compared with localised bacterial infection (2.9; 0-24.3 ng/ml), viral infection (0.8; 0-4.4 ng/ml), and non-infected controls (0; 0-4.9 ng/ml). Children with bacterial meningitis had a median procalcitonin of 25.5 (7.2-118.4 ng/ml). Area under the ROC curve was 0.96 for procalcitonin, 0.83 for C reactive protein, and 0.51 for leucocyte count. Cut off concentrations for optimum prediction of septic shock were: procalcitonin > 20 ng/ml and C reactive protein > 50 mg/litre. A procalcitonin concentration > 2 ng/ml identified all patients with bacterial meningitis or septic shock. CONCLUSION: In critically ill children the admission procalcitonin concentration is a better diagnostic marker of infection than C reactive protein or leucocyte count. A procalcitonin concentration of 2 ng/ml might be useful in differentiating severe bacterial disease in infants and children.

Adolescent↗
PubMed1996

Aerobic fitness testing: an update.

This study confirms that all three tests are reliable tools for the assessment of cardiorespiratory fitness and the prediction of aerobic capacity. While this particular study consisted of active, youthful subjects, subsequent studies at University College Chester have found similar findings with larger databases and a wider cross-section of subjects. The Astrand cycle test and Chester step test are submaximal tests with error margins of 5-15 per cent and therefore, not as precise as maximal testing. However, they still give a reasonably accurate reflection of an individual's fitness without the cost, time, effort and risk on the part of the subject. The bleep test is a low-cost maximal test designed for well-motivated, active individuals who are used to running to physical exhaustion. Used on other groups, results will not accurately reflect cardiorespiratory fitness values. While all three tests have inherent advantages and disadvantages, perhaps the most important factors are the knowledge and skills of the tester. Without a sound understanding of the physiological principles underlying these tests, and the ability to conduct an accurate assessment and evaluation of results in a knowledgeable and meaningful way, then the credibility of the tests and the results become suspect. However, used correctly, aerobic capacity tests can provide valuable baseline data about the fitness levels of individuals and data from which exercise programmes may be developed. The tests also enable fitness improvements to be monitored, help to motivate participants by establishing reasonable and achievable goals, assist in risk stratification and facilitate participants' education about the importance of physical fitness for work and for life. Since this study was completed, further tests have been repeated on 140 subjects of a wider age and ability range. This large database confirms the results found in this study.

Adult↗
PubMed1993

Proline isomerases function during heat shock.

The cyclophilins (CYPs) and FK506 binding proteins (FKBPs) are two families of distinct proline isomerases that are targets for a number of clinically important immunosuppressive drugs. Members of both families catalyze cis/trans isomerization of peptidyl-prolyl bonds, which can be a rate-limiting step during protein folding in vitro and in vivo. We demonstrate in Saccharomyces cerevisiae that heat shock causes a 2- to 3-fold increase in the level of mRNA encoded by the major cytoplasmic CYP gene, CYP1. The cloned CYP1 promoter confers heat-inducible expression upon a reporter gene, and transcriptional induction is mediated through sequences similar to the consensus heat shock response element. Disruption of CYP1 decreases survival of cells following exposure to high temperatures, indicating that CYP1 plays a role in the stress response. A second CYP gene, CYP2, encodes a cyclophilin that is located within the secretory pathway. Its expression is also stimulated by heat shock, and cells containing a disrupted CYP2 allele are more sensitive than wild-type cells to heat. By contrast, expression of the FKB1 gene, which encodes a cytoplasmic member of the yeast FKBP family, is neither heat responsive nor necessary for survival after exposure to heat stress.

Alleles↗
PubMed1993

Harold Griffith Memorial Lecture. The Griffith legacy.

1992 was the anniversary of Crawford Long's use of ether in 1842, and Griffith and Johnson's introduction of Intocostrin into anaesthetic practice in 1942. Harold Randall Griffith was born in Montreal in 1894 and died in 1985. He interrupted his medical studies to serve in the first world war and was awarded the Military Medal for gallantry at the battle of Vimy Ridge. Griffith qualified from McGill University in 1922. After spending a year studying homoeopathic medicine, he joined his father's general practice and became the anaesthetist to the Homoeopathic Hospital in Montreal. He succeeded his father as Medical Director of the hospital (now renamed the Queen Elizabeth Hospital) in 1936 and retired in 1966. Griffith was a superb clinical anaesthetist. He was an early advocate of detailed anaesthetic records, and was responsible for the introduction of both ethylene and cyclopropane into Canadian practice, later teaching himself to intubate under these two agents. Griffith was one of the first to be concerned with standards of patient care. He introduced postoperative recovery and intensive care units into Canadian practice and played a major role in postgraduate teaching. He was unstinting in his support of organisations designed to further the progress of anaesthesia and was the first President of the Canadian Anaesthetist's Society. He was one of those responsible for inaugurating the World Federation of Societies of Anaesthesiology and was President of the First World Congress of Anaesthesiology in 1955. It is remarkable that the introduction of curare into anaesthetic practice was delayed until 1942, since curare had been used in anaesthesia some 30 years previously. However, it was probably Griffith's confidence in his own clinical abilities which enabled him to seize the opportunity when it was offered.

Anesthesiology↗
PubMed1993

Specific cross-linking of the proline isomerase cyclophilin to a non-proline-containing peptide.

A peptide corresponding to an efficient peroxisomal targeting sequence, the carboxy terminal 12 amino acids of PMP20 from Candida boidinii, was employed as an affinity ligand to search for a peroxisomal targeting receptor. Two proteins from yeast extracts with apparent molecular masses of 20 and 80 kDa were detected by chemical cross-linking to radioiodinated peptide. Both proteins were present in cytosolic supernatants. The 20-kDa species did not cross-link to a control peptide with reversed sequence, whereas the 80-kDa protein cross-linked to both peptides. The cross-linking assay was used to purify the 20-kDa protein from Saccharomyces cerevisiae. Partial protein sequencing identified this protein as cyclophilin, the product of the CYP1 gene. This protein, a peptidyl-prolyl cis-trans isomerase, is the yeast homologue of the protein that mediates the immunosuppressant effects of the drug cyclosporin A (CsA). Cross-linking of peptide to cyclophilin was inhibited by CsA. The cross-linking of cyclophilin to the PMP20-derived peptide was unanticipated because the peptide contains no prolines. The CYP1-encoded protein was not required to target proteins to peroxisomes because this organelle appeared to be assembled normally in a CYP1-disrupted strain. Furthermore, the final three amino acids of the peptide, which are critical for peroxisomal sorting, were not required for cross-linking to cyclophilin. We conclude that either cyclophilin is playing a nonessential facilitating role in peroxisomal targeting or that the interaction of the targeting peptide to cyclophilin is mimicking an interaction with an unidentified substrate or effector of cyclophilin.

Amino Acid Isomerases↗
PubMed1992

Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein.

The gene for CD59 [membrane inhibitor of reactive lysis (MIRL), protectin], a phosphatidylinositol-linked surface glycoprotein that regulates the formation of the polymeric C9 complex of complement and that is deficient on the abnormal hematopoietic cells of patients with paroxysmal nocturnal hemoglobinuria, consists of four exons spanning 20 kilobases. The untranslated first exon is preceded by a G+C-rich promoter region that lacks a consensus TATA or CAAT motif. The second exon encodes the hydrophobic leader sequence of the protein, and the third exon encodes the amino-terminal portion of the mature protein. The fourth exon encodes the remainder of the mature protein, including the hydrophobic sequence necessary for glycosyl-phosphatidylinositol anchor attachment. The structure of the CD59 gene is very similar to that encoding Ly-6, a murine glycoprotein with which CD59 has some structural similarity. The striking similarity in gene structure is further evidence that the two proteins belong to a superfamily of proteins that may also include the urokinase plasminogen-activator receptor and a squid glycoprotein of unknown function.

Amino Acid Sequence↗
PubMed1992

Aerobic capacity.

Explore the source record for details and available documents.

Adolescent↗
PubMed1990

A naturally occurring gamma globin gene mutation enhances SP1 binding activity.

Transcription of the human fetal globin genes in erythroid cells is tightly regulated during different stages of development and differentiation. Two naturally occurring mutations 202 base pairs upstream of the duplicated gamma globin genes are associated with incorrectly regulated gamma globin gene gene expression; elevated levels of fetal globin are synthesized during adult life. A C-to-G base substitution upstream of the G gamma-globin gene is highly correlated with a dramatic increase in gene expression. It increases the similarity of the region to the consensus Sp1 recognition site. We determined that the mutated DNA had a 5- to 10-fold-higher affinity for Sp1 than did normal gamma globin gene sequence. We also observed a reduction in normal factor-binding activity. A different substitution at -202, C to T, upstream of the A gamma-globin gene was associated with a more moderate increase in fetal globin expression. This mutation decreased the similarity of the sequence to an Sp1 recognition site. We determined that it did not result in enhanced Sp1 binding but did alter normal factor binding. We suggest that these changes in nuclear protein-binding properties detected in vitro are responsible for the enhanced gamma globin gene expression found in -202 G gamma beta + patients with hereditary persistence of fetal hemoglobin.

Base Sequence↗