An unusual complication of transvenous temporary pacing.
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Biomedical subjects
Publications and source records attributed to M James.
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BACKGROUND: This study evaluated the costs of acute normovolaemic haemodilution (ANH) and intraoperative cell salvage (ICS) versus homologous blood transfusion in aortic surgery in a prospective multicentre randomized trial. METHODS: One hundred and forty-five patients were randomized either to standard transfusion practice (homologous) or to a combination of ANH and ICS (autologous). Costs for each inpatient admission were identified. Cell salvage costs were assigned on the assumption that 50 operations were done each year employing a trained cell salvage operator. The results were analysed statistically using bias-corrected bootstrap analysis. RESULTS: Patients who had transfusion of homologous blood received some 251 units and those having a homologous transfusion received 103 units (P = 0.008). There was no difference in morbidity, mortality and duration of hospital stay. Transfusion-related mean costs were similar at 340 UK pounds for patients having a homologous transfusion and 357 UK pounds for those receiving autologous blood (mean difference 17 UK pounds (95 per cent confidence interval [c.i.]--184 UK pounds to 174 UK pounds); P not significant). There was also no significant difference in mean overall costs: 5859 UK pounds for homologous and 5384 UK pounds for autologous transfusion (mean difference--475 UK pounds (95 per cent c.i.--2231 UK pounds to 1342 UK pounds)). Sensitivity analysis showed that costs remained similar for 20 and 150 operations per annum. Exclusion of a dedicated cell salvage operator reduced autologous transfusion costs but did not have a significant impact on overall cost. CONCLUSION: Autologous transfusion is cost neutral in aortic surgery even when surgical activity is low.
This article reviews the current status of retinopathy screening schemes in the UK. There is evidence that high-quality diabetic retinopathy screening schemes are in existence but provision is patchy. Many health authorities have ad hoc screening programmes reaching only about 60% of patients, with unacceptable or undocumented efficacy and minimal quality control. Several models of screening are currently in use with the current preferred option being camera-based screening. Digital imaging systems offer the best prospects for image acquisition, although at present evidence of adequate effectiveness only exists for 35 mm film-based systems. The final report of the National Diabetic Retinopathy Screening Programme commissioned by the UK National Screening Committee for inclusion into the national service framework for diabetes, is thus eagerly awaited and should set standards for screening programmes, in order to improve the care of all those with diabetes. Quality assurance will be the main driver in the immediate future of improvements in screening programmes. Research data will provide the evidence to refine techniques and set targets in the longer term, with the emphasis on cost-effectiveness and quality of life.
Eukaryotic tRNAs are transcribed as precursors. A 5'-end leader and 3'-end trailer are endonucleolytically removed by RNase P and 3'-tRNase before 3'-end CCA addition, aminoacylation, nuclear export and translation. 3'-End -CC can be a 3'-tRNase anti-determinant with the ability to prevent mature tRNA from recycling through 3'-tRNase. Twenty-two tRNAs punctuate the two rRNAs and 13 mRNAs in long, bidirectional mitochondrial transcripts. Accurate mitochondrial gene expression thus depends on endonucleolytic excision of tRNAs. Various mitochondrial diseases and syndromes could arise from defective tRNA end processing. The U7445C substitution in the human mitochondrial L-strand transcript (U74C directly following the discriminator base of tRNA(Ser(UCN))) causes non-syndromic deafness. The sequence of the precursor (G/UCU) becomes G/CCU, resembling a 3'-tRNase anti-determinant. We demonstrate that a tRNA(Ser(UCN)) precursor with the U7445C substitution cannot be processed in vitro by 3'-tRNase from human mitochondria. A 3'-end processing defect in this tRNA precursor could thus be responsible for mitochondrial disease.
PURPOSE: To examine the techniques used for the treatment of contracture in the context of current scientific knowledge of muscle. METHOD: Synthesis of data available from MEDLINE, RECAL, EMBASE, the Cochrane Library and relevant texts. RESULTS: The development of contractures through immobilisation, muscle weakness and spasticity is described. The effects of passive stretching, continuous passive movement, serial plastering, splinting, electrical stimulation, botulinum injections and surgical tenotomies in the treatment of contractures in persons with neurological and orthopaedic conditions are identified. The strengths and weaknesses of these modalities are discussed. CONCLUSION: Predisposing factors persist after treatment of contractures thus for treatment to be effective long-term management programmes need to be developed. New treatment techniques, used in series or combined, offer the prospect of improved management of contracture. Scientific and clinical research is needed to investigate the effect of contracture treatment.
OBJECTIVE: To determine the care pathways and implications of offering mothers the choice of external cephalic version (ECV) at term for singleton babies who present with an uncomplicated breech pregnancy versus assisted breech delivery or elective caesarean. DESIGN: A prospective observational audit to construct a decision analysis of uncomplicated full term breech presentations. SETTING: The North Staffordshire NHS Trust. SUBJECTS: All women (n = 176) who presented at full term with a breech baby without complications during July 1995 and June 1997. MAIN OUTCOME MEASURES: The study determined to compare the outcome in terms of the costs and cost consequences for the care pathways that resulted from whether a women chose to accept the offer of ECV or not. All the associated events were then mapped for the two possible pathways. The costs were considered only within the hospital setting, from the perspective of the health care provider up to the point of delivery. RESULTS: The additional costs for ECV, assisted breech delivery and elective caesarean over and above a normal birth were 186.70 pounds sterling, 425.36 pounds sterling and 1,955.22 pounds sterling respectively. The total expected cost of the respective care pathways for "ECV accepted" and "ECV not accepted" (including the probability of adverse events) were 1,452 pounds sterling and 1,828 pounds sterling respectively, that is the cost of delivery through the ECV care pathways is less costly than the non ECV delivery care pathway. CONCLUSIONS: Implementing an ECV service may yield cost savings in secondary care over and above the traditional delivery methods for breech birth of assisted delivery or caesarean section. The scale of these expected cost savings are in the range of 248 pounds sterling to 376 pounds sterling per patient. This converts to a total expected cost saving of between 43,616 pounds sterling and 44,544 pounds sterling for the patient cohort considered in this study.
Six different lectin probes were used to examine alterations of the cell surface carbohydrates in the chinchilla eustachian tube (ET) lumen subsequent to the intranasal (i.n.) challenge with the Streptococcus pneumoniae parent strain, D39, or its isogenic derivative, DeltaNA1, which is deficient in neuraminidase NanA. The labelling pattern revealed that the binding of wheat germ agglutinin (WGA), Erythrina cristagalli lectin (ECL), peanut agglutinin (PNA), Bandeiraea simplicifolia lectin II (BSL II) and succinylated wheat germ agglutinin (SWGA) were increased in the lumenal surface of the ET in the D39 inoculated cohort compared to the uninfected control, which indicated that N-acetylglucosamine (GlcNAc) and D-galactose residues were exposed. Concurrently, decreased labelling with Sambucus nigra agglutinin (SNA) indicated that there were few sialic acid residues remaining in the ET epithelium subsequent to i.n. inoculation with D39. The DeltaNA1 neuraminidase deficient mutant, however, did not induce any significant changes in the lectin labelling patterns, and was comparable to that of the control cohort. We propose that products of the nanA gene have a significant impact on the changes of the carbohydrate moieties in the ET epithelium and may be responsible for the previously reported increased ability of the D39 parent to colonize the nasopharynx and invade the middle ear.
NHE-RF, a regulatory cofactor for NHE (Na(+)-H(+) exchanger) type 3, interacts with ion transporters and receptors through its PDZ domains and with the MERM proteins (merlin, ezrin, radixin and moesin) via its carboxyl terminus. Thus, NHE-RF may act as a multifunctional adaptor protein and play a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin cytoskeleton. NHE-RF expression is up-regulated in response to estrogen in estrogen receptor-positive breast carcinoma cell lines, suggesting that it may be involved in estrogen signaling. To further understand NHE-RF function and its possible role in estrogen signaling, we analyzed NHE-RF expression in normal human tissues, including cycling endometrium, and in breast carcinomas, tissues in which estrogen plays an important role in regulating cell growth and proliferation. NHE-RF is expressed in many epithelia, especially in cells specialized in ion transport or absorption, and is often localized to apical (luminal) membranes. NHE-RF expression varies markedly in proliferative versus secretory endometrium, with high expression in proliferative (estrogen-stimulated) endometrium. Furthermore, estrogen receptor status and NHE-RF expression correlate closely in breast carcinoma specimens. These findings support a role for NHE-RF in estrogen signaling.
Seventy-seven frequent attenders at an emergency department (ED) in an inner-city hospital in the UK (defined as seven or more visits in the previous 12 months) were compared with 182 patients who were attending the same department on a routine basis. Patients completed the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Short Form (SF)-36. Information was obtained on 64% of the frequent attenders and 45% underwent a detailed psychiatric assessment. Of the frequent attenders, 45% had psychiatric disorder and 49% had some form of an alcohol-related disorder. Compared with routine attenders, frequent attenders reported lower health status, had more psychiatric disorder (odds ratio: OR=8.2, 95% confidence interval: CI=3.8--18.1), had more general hospital admissions (OR=19.9, 95% CI=8.3--47.8), more psychiatric admissions (OR=167.5, 95% CI=9.5--2959.0), and more GP visits (95% CI for difference=-10.2 to -5.7). There was no evidence that frequent attenders had more somatisation than routine attenders. Specific treatment and management strategies need to be developed for this group of patients, although a substantial proportion may be difficult to engage in the treatment process.
Discrimination between supraventricular tachycardia (SVT) with aberrant conduction from ventricular tachycardia (VT) is vital for the safe and effective management of both conditions. Electrocardiographic algorithms for the differentiation of broad complex tachycardia are complex and difficult to implement in the acute setting, with misdiagnosis occurring in up to 40% of acute presentations. This case study shows the potential for echocardiographic colour kinesis (eck) to support electrocardiographic differentiation. A 74-year old man in sinus rhythm with left bundle branch block (lbbb), a history of myocardial infarction and recurrent sustained VT underwent eck analysis of wall motion propagation during a programmed electrical ventricular stimulation study. Sequential 40 ms time frames of echocardiographic colour coded endocardial wall motion velocity were recorded on video during both induced VT of lbbb configuration and near isochronic atrially paced tachycardia in lbbb. During VT there was initial eck propagation of ventricular septal wall motion from the apex to the atria secondary to electrical depolarisation. During atrially paced tachycardia initial eck motion developed in the interatrial septum and atrial wall followed by propagation in the ventricular endocardial septal wall motion from the atria toward the ventricular apex. This eck technique potentially could be used to support the electrocardiographic diagnosis of a broad complex tachycardia.
OBJECTIVES: To evaluate how well women learned and retained information given to them by either a leaflet or a computer-generated information system, and which system they preferred to use for obtaining information about urinary symptoms. SUBJECTS AND METHODS: Forty women answered 11 questions on the aetiology, investigation and treatment of lower urinary tract symptoms. They were then randomized to use one of the information systems for 20 min, after which they answered the same urological questions. The women then crossed over to use the other information system for 20 min and afterwards completed a preference questionnaire. RESULTS: The mean baseline scores from a possible total of 11 were 3.9 and 4.3 for the computer and leaflet groups, respectively. The mean improvements in scores were 3.6 (P < 0.001) and 2.8 (P < 0.001) for the computer and leaflet groups, respectively. Both information systems were well liked by all of the women and 26 (65%) said they would prefer to use a computer-generated system in the future if given a choice. CONCLUSIONS: Women significantly increased their knowledge of urinary problems after using a computer-generated information system or a leaflet. Although there were few subjects, there appeared to be a trend for the computer system to be both better liked and slightly more effective.
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To define the role of nontypeable Haemophilus influenzae (NTHI) lipooligosaccharide (LOS) in the induction of proinflammatory cytokine gene expression during otitis media, we compared the abilities of formalin-killed NTHI strain 2019 and its LOS htrB and rfaD mutants to stimulate human middle ear epithelial (HMEE) cell cytokine and chemokine gene expression and production in vitro. Strain DK-1, an rfaD gene mutant, expresses a truncated LOS consisting of only three deoxy-D-manno-octulosonic acid residues, a single heptose, and lipid A. Strain B29, an isogenic htrB mutant, possesses an altered oligosaccharide core and an altered lipid A. HMEE cells were incubated with formalin-killed NTHI 2019, B29, or DK-1. The supernatants and the cells were collected at 2, 4, 8, and 24 h after stimulation. Expression of genes for the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin lbeta (IL-1beta), and IL-6 and for the chemokines macrophage inflammatory protein 1beta (MIP-1beta), monocyte chemotactic peptide 1 (MCP-1), and IL-8 was quantitated by real-time PCR. NTHI B29 did not significantly stimulate any cytokine or chemokine mRNA expression in HMEE cells. In striking contrast, NTHI 2019 induced up to 105-, 139-, and 187-fold increases in HMEE cell expression of IL-1beta, TNF-alpha, and MIP-1beta, respectively (P < 0.01 [2019 versus B29]). NTHI 2019 also induced upregulation of IL-8, IL-6, and MCP-1 mRNA expression (by 26-, 44-, and 14-fold, respectively [P < 0.05 (2019 versus B29)]). The significant induction of cytokine genes was confirmed by quantitating the secretion of cytokines in culture supernatants with an enzyme-linked immunosorbent assay. There were no significant differences in mRNA expression of IL-8, IL-6, and MCP-1 between the 2019- and DK-1-treated groups. The low levels of gene transcripts observed after incubation of HMEE cells with B29 indicate that products of the disrupted NTHI htrB LOS gene may play a major role in induction of these particular inflammatory mediators.
Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDa proteins that are ubiquitous and are largely conserved in amino acid sequence among all organisms. The principal heat-shock proteins that have chaperone activity (that is, they protect newly made proteins from misfolding) belong to five conserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs (which include alpha crystallin) can form large multimeric structures and have a wide range of cellular functions, including endowing cells with thermotolerance in vivo and being able to act as molecular chaperones in vitro; sHSPs do this by forming stable complexes with folding -or unfolding--intermediates of their protein substrates, probably the molten globule. This paper includes: a brief survey of the chaperone family, the small heat shock protein superfamily, transcription of sHSPs, sequence comparisons and structural models of small heat shock proteins--structural elements as potential drug targets, sHSPs as chaperone-like proteins, alpha crystallin chaperone-like activity, conformational diseases--the role of alpha crystallin small heat shock protein superfamily proteins, post-translational modification and useful pharmacological agents. Functionality of small heat shock proteins--targets and diseases where pharmacologically active agents are of importance, alpha crystallin--small heat shock proteins and prion diseases: specific targets for diagnostic tests and drug development, details of some specific small heat shock proteins as drug targets, structural and functional implications for treatment.
The efficacy, safety, and tolerability of twice-daily fluticasone propionate (Cutivate) cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, were compared in 125 patients with moderate-to-severe psoriasis in a 4-week, multicenter, double-blind, randomized, active-control study. Clinical assessments of response to therapy, made at weekly intervals, included physicians' gross assessment of clinical response, improvement in signs and symptoms, and patients' assessment of treatment effects. Based on physicians' gross assessment, fluticasone propionate cream was superior to hydrocortisone-17-butyrate cream at day 22 (after 3 weeks' treatment) and at the end-of-treatment visit (P < .05). Cleared, excellent, or good end-of-treatment response rates were 50/63 (79%) for fluticasone propionate compared with 41/60 (68%) for hydrocortisone-17-butyrate. Adverse events were limited to mild-to-moderate pruritus with fluticasone propionate (3.2%) and hydrocortisone-17-butyrate (1.7%) and mild skin warmth with hydrocortisone-17-butyrate (1.7%).
OBJECTIVE: To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. DESIGN: Cost effectiveness analysis. SETTING: Liverpool. SUBJECTS: A target population of 5000 diabetic patients invited for screening. MAIN OUTCOME MEASURES: Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. RESULTS: Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was 209 pound sterling (sensitivity 89%, specificity 86%, compliance 80%, annual cost 104996 pound sterling) and of the opportunistic programme was 289 pound sterling (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost 99 981 pound sterling). The incremental cost effectiveness of completely replacing the opportunistic programme was 32 pound sterling. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. CONCLUSION: Replacing existing programmes with systematic screening for diabetic eye disease is justified.