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C Bartlett

Publications and source records attributed to C Bartlett.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intervention thresholds and ceilings can determine the haemoglobin outcome distribution in a haemodialysis population.

We have explored the consequences of setting different thresholds and ceilings for erythropoietin dose changes in two randomized controlled studies of renal anaemia management based on an established algorithm. STUDY 1: A large (n=236) unselected haemodialysis cohort was randomized to monthly intervention (increased erythropoietin (Epo)) at haemoglobin (Hb) levels falling below either 10.5 g/dl (group A) or 11.5 g/dl (group B) and followed for 6 months. The mean Hb was 0.6 g/dl higher in the 11.5 g/dl threshold group (11.1 g/dl vs 11.7 g/dl) at 6 months (P=0.001++). The Epo dose did not differ between them (median 133 IU/kg/week, Interquartile range (IQR) 86-217 and 140, IQR 74-227 respectively) (P=NS(**)). STUDY 2: A large (n=211) unselected haemodialysis cohort was randomized to a reduction in Epo dose at Hb levels above either 12.0 g/dl (group C) or 13.0 g/dl (group D). The Hb outcome at 8 months differed between group C (mean 11.5 g/dl, SD 1.4) and group D (12.2, SD 2.1) (P=0.03++). The Epo dose did not significantly differ between groups C and D (median 60 IU/kg/week, IQR 32-142 and 71, IQR 38-117 respectively) (P=NS(**)). Study 1 showed that an intervention threshold of 11.0 g/dl with a mean Hb outcome of 11.6 g/dl and SD 1.6 g/dl would produce the desired UK Renal Association Standards outcome of 85% Hb > or =10.0 g/dl. Study 2 demonstrated that a ceiling of 12.0 g/dl narrowed the range of Hb values (P:<0.001##), achieving a SD of 1.37 g/dl, and reduced the number of patients with a Hb >13.0 g/dl from 25 to 12%. This narrowing of the distribution has cost implications for reaching minimum standards in a haemodialysis population. Formal use of threshold and ceiling values for intervention within an anaemia management system enabled the haemodialysis population outcome mean and SD to be literally prescribed.

Adult↗
PubMed1999

Nonpeptidic SH2 inhibitors of the tyrosine kinase ZAP-70.

The synthesis of a series of 1,2,4-oxadiazole analogs is discussed along with their ZAP-70 SH2 inhibitory activity. The tyrosine moiety in the original series has been replaced with nonpeptidic functional groups without a substantial loss of binding affinity.

Enzyme Inhibitors↗
PubMed1999

Discovery of potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70.

A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity zeta-1-ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH(2), wherein pY refers to phosphotyrosine) some of the best 1,2, 4-oxadiazole analogues are approximately 1 order of magnitude less active. This series of compounds displays an unprecedented level of selectivity over the closely related tyrosine kinase Syk, as well as other SH2-containing proteins such as Src and Grb2. Gel shift studies using a protein construct consisting only of C-terminal ZAP-70 SH2 demonstrate that these compounds can effectively engage this particular SH2 domain.

Enzyme Inhibitors↗
PubMed1999

Markers of inappropriate placement in acute psychiatric inpatient care: a five hospital study.

BACKGROUND: Previous researchers in the UK have measured the prevalence of the 'inappropriateness' of acute adult psychiatric inpatient placements by eliciting the judgements of health professionals. We extended the methodology by identifying inpatient sub-groups with stable characteristics that were associated with elevated risk of inappropriate placement, and by calculating the level of that risk. METHODS: A 1-day census was taken in five hospitals. Using a structured instrument, consultant psychiatrists recorded judgements on current placements, recommended alternative placements and stated why alternatives had not been used. Judgements were obtained for 100% of the 261 inpatients. Risk ratios and adjusted odds ratios were calculated to identify sub-groups that were at high risk. RESULTS: Eighty-eight inpatients were inappropriately placed, a point prevalence of 34% (95% CI 28-40%). Consultants recorded that services outside hospital, if available, could have supported most of these inpatients as an alternative to at least part of their hospital stay. Diagnostic rather than socio-demographic or administrative characteristics, in particular primary diagnoses of substance-related disorder, personality disorder, anxiety/stress, and schizophrenia with co-morbid substance misuse, were the strongest markers of elevated risk. CONCLUSIONS: The point prevalence of inappropriate placement within the British mental health-care system is considerable. Diagnostic categories are reasonable pragmatic markers. Further research should aim to identify a strong marker of risk within the numerically large sub-group of schizophrenia without substance misuse.

Adolescent↗
PubMed1999

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network.

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.

Adolescent↗
PubMed1998

Trauma admissions in the elderly: how does a patient's age affect the likelihood of their being admitted to hospital after a fracture?

In two projects we have studied patients presenting to Accident and Emergency (A&E) departments with a fracture, to examine how their age influences their likelihood of admission. Over 1 year from April 1994 we collected data on all 6467 Cardiff residents who presented to the city's A&E department with a fracture. In total 1226 (19%) were admitted. Overall, only 12% of those under 65, but 47% of older patients required admission. This was largely a reflection of the age-distribution of hip fracture, an injury for which admission is inevitable. In a subsequent study of eight A&E departments in South Wales we therefore considered the proportion of patients admitted following fractures at specific anatomical sites. In people over the age of 55 we identified 6889 fractures, 2115 (31%) of which led to admission. After standardisation to control for the age-distribution of incidence for different fracture sites, we found that the likelihood of admission was 22% greater for people aged over 65 years. Elderly people very often require hospital admission after a fracture, primarily as a consequence of the types of fractures that they tend to sustain. Admissions directly attributable to the effects of age and age-related medical, psychiatric and social comorbidity appear of more limited significance.

Adolescent↗
PubMed1997

Protein structure-based design, synthesis, and biological evaluation of 5-thia-2,6-diamino-4(3H)-oxopyrimidines: potent inhibitors of glycinamide ribonucleotide transformylase with potent cell growth inhibition.

The design, synthesis, biochemical, and biological evaluation of a novel series of 5-thia-2,6-diamino-4(3H)-oxopyrimidine inhibitors of glycinamide ribonucleotide transformylase (GART) are described. The compounds were designed using the X-ray crystal structure of human GART. The monocyclic 5-thiapyrimidinones were synthesized by coupling an alkyl thiol with 5-bromo-2, 6-diamino-4(3H)-pyrimidinone, 20. The bicyclic compounds were prepared in both racemic and diastereomerically pure forms using two distinct synthetic routes. The compounds were found to have human GART KiS ranging from 30 microM to 2 nM. The compounds inhibited the growth of both L1210 and CCRF-CEM cells in culture with potencies down to the low nanomolar range and were found to be selective for the de novo purine biosynthesis pathway. The most potent inhibitors had 2,5-disubstituted thiophene rings attached to the glutamate moiety. Placement of a methyl substituent at the 4-position of the thiophene ring to give compounds 10, 18, and 19 resulted in inhibitors with significantly decreased mFBP affinity.

Acyltransferases↗
PubMed1997

Single-channel properties of the recombinant skeletal muscle Ca2+ release channel (ryanodine receptor).

We report transient expression of a full-length cDNA encoding the Ca2+ release channel of rabbit skeletal muscle sarcoplasmic reticulum (ryanodine receptor) in HEK-293 cells. The single-channel properties of the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate-solubilized and sucrose gradient-purified recombinant Ca2+ release channels were investigated by using single-channel recordings in planar lipid bilayers. The recombinant Ca2+ release channel exhibited a K+ conductance of 780 pS when symmetrical 250 mM KCl was used as the conducting ion and a Ca2+ conductance of 116 pS in 50 mM luminal Ca2+. Opening events of the recombinant channels were brief, with an open time constant of approximately 0.22 ms. The recombinant Ca2+ release channel was more permeable to Ca2+ than to K+, with a pCa2+/pK+ ratio of 6.8. The response of the recombinant Ca2+ release channel to various concentrations of Ca2+ was biphasic, with the channel being activated by micromolar Ca2+ and inhibited by millimolar Ca2+. The recombinant channels were activated by ATP and caffeine, inhibited by Mg2+ and ruthenium red, and modified by ryanodine. Most recombinant channels were asymmetrically blocked, conducting current unidirectionally from the luminal to the cytoplasmic side of the channel. These data demonstrate that the properties of recombinant Ca2+ release channel expressed in HEK-293 cells are very similar, if not identical, to those of the native channel.

Adenosine Triphosphate↗
PubMed1997

Intrapelvic dislocation of the left hemipelvis as a complication of the pelvic "C" clamp: a case report and review.

High-energy pelvic trauma, with posterior pelvic disruption, produces high morbidity and mortality rates. Part of the initial resuscitation has included an anterior external fixator to close the pelvic ring, thereby decreasing blood loss and reducing mortality. However, this technique has been found to be less efficacious in certain situations. This has stimulated an interest in alternative methods of stabilization, which has led to the recent development of the emergency pelvic "C" clamp. We present one of the potential pitfalls of this new device, discuss pertinent clinical and biomechanical studies, and offer suggestions regarding its use.

Accidents, Traffic↗
PubMed1996

Salm-Net facilitates collaborative investigation of an outbreak of Salmonella tosamanga infection in Europe.

Twenty-eight cases of Salmonella tosamanga infection were identified in six western European countries during the first half of 1995. Salm-Net, a European system for collaborative surveillance of gastrointestinal infection, detected the outbreak and coordinated its investigation. There were 28 cases, 14 of each sex, with a broad age distribution. Interviews with cases to identify common food and other exposures failed to generate a working hypothesis. The initial cluster occurred in a period of eight weeks and, since only one further case occurred in June, the investigation was closed. This incident shows that Salm-Net is effective in identifying international outbreaks of human salmonellosis. Practical difficulties in the field investigation of the outbreak are discussed.

Adult↗
PubMed1996

An international investigation of an outbreak of Legionnaires disease among UK and French tourists.

Five cases of legionnaires disease and one death were associated with four members of a tour group from the United Kingdom (UK) and one French tourist who all visited Spain in the spring of 1993. The UK group stayed at four hotels, one of which was also used by the French tourist. Phenotypic and genotypic comparison of isolates of Legionella pneumophila obtained from one of the UK cases and the French patient demonstrated that they were indistinguishable from each other and from environmental isolates obtained from the water supply of the hotel at which all five cases had stayed. A cohort study of the UK tour group was carried out to determine the extent of the outbreak and showed that three further members of the group had respiratory illness but were serologically negative to legionella infection. International participation in this investigation has highlighted the value of a European surveillance scheme and the benefit of microbiological collaboration between legionella reference laboratories in Europe.

Aged↗
PubMed1994

1H NMR studies on an Asn-linked glycopeptide. GlcNAc-1 C2-N2 bond is rigid in H2O.

The conformation of an Asn-linked glycopeptide in H2O was studied by two-dimensional 1H NMR. Nonexchangeable proton and exchangeable amide (NH) proton resonances were assigned for the hen ovomucoid glycopeptide 1, Ser-Ile-Glu-Phe-Gly-Thr-Asn Ile-Ser-Lys, with pentasaccharide Man alpha 1-3 (Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc beta 1-NH attached to the Asn7 gamma-carboxamide. The pentasaccharide increases the local correlation times of amino acid residues near the N-glycosylation site. Nuclear Overhauser effect (NOE) measurements on 1 and the corresponding Man3-GlcNAc2 pentasaccharide 3 show that the attached peptide does not perturb O-glycoside conformation. Sequential dNN (i, i + 1) NOEs in the Thr6-Ser9 region indicate populations of folded structure near the N-glycosylation site of both glycopeptide 1 and aglycosyl peptide 2. However, the Man3GlcNAc2 pentasaccharide does not dramatically affect the average conformation of either the peptide backbone or the Asn7 side chain. GlcNAc NH protons were studied at pH 3.0; and NOE and 3JNH data were used to constrain the glycopeptide's GlcNAc-1 side chain dihedral angle (tau) (C1-C2-N2-C7(Ac)). The glycopeptide's core GlcNAc-1 C2-N2 side chain bond is not flexible in H2O. A strong GlcNAc-1 NH2-H3 NOE, a medium strength NH2-H1 NOE, and a weak NH2-H2 interaction suggest that GlcNAc-1 has a rigid C2-N2 bond, with tau between 95 and 115 degrees. No evidence was found for intramolecular hydrogen bonds restricting this C2 side chain torsion. It may be that GlcNAc-1's rigid planar N-glycosidic linkage limits the conformational space available to the adjacent C2 acetamido side chain.

Acetylglucosamine↗
PubMed1994

Comparison of approximate and iterative methods to calculate the efficiency of haemodialysis as KT/V.

Dialysis dose is given by the index KT/V, where K is the dialyser urea clearance, T the duration of dialysis and V the notional urea distribution volume. KT/V may be calculated using the single pool model and an iterative calculation which requires a computer program. Three estimates of KT/V, each based on simple correction of the log ratio in (C0/C1), where C0, C1 denote the pre- and post-dialysis blood urea concentrations in mg/ml, were developed and compared with the values of KT/V given by iteration. The first estimate was given by adding two terms to the log ratio to account for the effect of ultrafiltration and urea generation while the second and third estimates were given by increasing the log ratio by 12.5% and 15% respectively. All estimates gave good agreement when compared with the iterative technique by Bland-Altman analysis for 27 patients on standard 4 hour dialysis treatment using 4 different dialysers (0.71 < KT/V < 1.62). The mean difference in all cases was less than 0.025 and the differences were not clinically significant. The use of these approximate formulae to estimate dialysis efficiency avoids the need for complex calculation or additional blood samples.

Adult↗
PubMed1993

The cost of infection in surgical patients: a case-control study.

To determine the excess hospital cost attributable to hospital acquired infection in a UK hospital 67 surgical patients with hospital acquired infection (HAI) were matched with uninfected controls on the primary features of the first operative procedure and primary diagnosis, and on the secondary features of sex, age and surgical service. Costs were calculated from the hospital's unit costs for pathology, radiology and for the cost of one day's extra stay. The mean cost of one day of antibiotic therapy was also measured. In infected patients there was a significant increase in the length of hospital stay of 8.2 days with a mean extra cost per patient of 1041 pounds (P < 0.001). Microbiology, haematology, chemical pathology and radiology requests were all significantly increased with a mean extra cost per infected patient of 10.4 pounds, 7.8 pounds, 96. pounds, and 3.3 pounds, respectively. Antibiotic therapy contributed significantly to the extra costs (44 pounds per infected patient). The mean extra cost per patient was highest in orthopaedic patients (2646 pounds) and least in gynaecology patients (404 pounds). For the infections with significantly increased cost, multiple infections carried the greatest (3362 pounds), and urinary tract infections the least (467 pounds) cost. Hospital length of stay was the greatest contributor to the cost and accounted for 95% of the extra cost in orthopaedics, 94% in gynaecology and 92% in general surgery and urology. Antibiotic therapy was the second most significant contributor to cost and, with the exception of urinary tract infection and infections in gynaecology, was at least five times more per patient than requests for microbiology, haematology, chemical pathology or radiology.

Case-Control Studies↗