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Biomedical subjects

M Elliott

Publications and source records attributed to M Elliott.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mitral valve replacement in children: mortality, morbidity, and haemodynamic status up to medium term follow up.

OBJECTIVE: To investigate the outcome of mechanical mitral valve replacement in children after up to 11 years of follow up. DESIGN: Retrospective analysis of case records. Operative survivors underwent echocardiographic studies to define current haemodynamic status and prosthetic valve function. SETTING: Tertiary referral centre. PATIENTS: All 54 children who underwent mitral valve replacement between January 1987 and December 1997. RESULTS: 30 day mortality was 20.3% and was associated with small valve size and supra-annular position. The actuarial freedom from the following events at five years (70% confidence interval (CI)) was: death, including 30 day mortality and transplantation, 68% (70% CI 62% to 75%); bleeding, 89% (70% CI 84% to 94%); non-structural valve dysfunction and reoperation, 92% (70% CI 87% to 97%). The incidence of endocarditis and thromboembolism was low and there was no structural valve failure. Event-free survival was 52% (70% CI 45% to 60%). Low weight, young age, and small valve size increased the chance of death or reoperation. On echocardiography, left ventricular dilatation and wall motion abnormalities were often observed. A high mean gradient over the prosthesis was associated with small valve size but not with length of follow up. CONCLUSIONS: With the use of mechanical prostheses for mitral valve replacement in children, the problem of structural valve failure is no longer an issue. However, the procedure is still associated with a high complication rate, both at surgery and during follow up, and should therefore be reserved for patients in whom valve repair is not technically feasible.

Adolescent↗
PubMed2000

Quality of life in children following mitral valve replacement.

OBJECTIVE: To measure the health related quality of life (QoL) following mitral valve replacement in childhood. DESIGN: Cross sectional study. SETTING: Tertiary referral centre. METHODS: 19 patients, median age (range) 14.4 (9.7-25.4) years, were studied at a median of 7.6 (0.5-11.2) years after their most recent mitral valve replacement. General health status was measured using age specific validated questionnaires. Ten children aged between 9-15 years completed the child health related quality of life questionnaire, and for nine older patients the UK version of the short form 36 was used. Specific questions were added to the existing questionnaires to study the effect of long term anticoagulation treatment. RESULTS: All patients in the younger age group reported impaired QoL. Five rated their QoL within the range of children with chronic physical disabilities, and in the remaining five it was worse. In the older age group, all but two patients perceived their QoL as normal or near normal compared with a reference population matched for sex and age. Having regular blood tests had a negative effect on QoL in three young children, and one older patient reported impaired QoL related to taking daily warfarin tablets. CONCLUSIONS: In this small group, the effect of mitral valve replacement on QoL appears to be age specific, with more impairment in younger children. Long term anticoagulation treatment is well tolerated in most patients.

Adolescent↗
PubMed2000

Lip-reading ability and patterns of cortical activation studied using fMRI.

Lip-reading is a complex cognitive skill with large individual differences in performance. The basis of these individual differences remains poorly understood. Functional magnetic resonance imaging (fMRI) techniques allows brain activation accompanying complex cognitive activities to be studied noninvasively. In the present paper, fMRI was used to study the patterns of cortical activation that occur during the silent lip-reading of connected speech and to investigate whether there are detectable differences in activation between subjects with widely differing lip-reading abilities. From a cohort of 26 volunteers, nine subjects who fell into three distinct lip-reading ability groups were selected. Brain activation was measured in two conditions: an experimental condition where subjects attempted to lip-read sentences; and a baseline condition where subjects passively viewed a static image of a talker's face. Relative to the baseline condition, lip-reading induced activation in several cortical areas, including the auditory cortices, despite the lack of an auditory component to the task. In comparison to the better two groups of lip-readers, subjects in the poorest group displayed significantly less activation in superior and middle temporal gyrus, but not inferior temporal gyrus. These preliminary results justify more extensive investigations of the cortical basis of individual differences in lip-reading.

Adult↗
PubMed2000

Do consumer reports of health plan quality affect health plan selection?

OBJECTIVE: To learn whether consumer reports of health plan quality can affect health plan selection. DATA SOURCES: A sample of 311 privately insured adults from Los Angeles County. STUDY DESIGN: The design was a fractional factorial experiment. Consumers reviewed materials on four hypothetical health plans and selected one. The health plans varied as to cost, coverage, type of plan, ability to keep one's doctor, and quality, as measured by the Consumer Assessment of Health Plans Study (CAHPS) survey. DATA ANALYSIS: We used multinomial logistic regression to model each consumer's choice among health plans. PRINCIPAL FINDINGS: In the absence of CAHPS information, 86 percent of consumers preferred plans that covered more services, even though they cost more. When CAHPS information was provided, consumers shifted to less expensive plans covering fewer services if CAHPS ratings identified those plans as higher quality (59 percent of consumers preferred plans covering more services). Consumer choices were unaffected when CAHPS ratings identified the more expensive plans covering more services as higher quality (89 percent of consumers preferred plans covering more services). CONCLUSIONS: This study establishes that, under certain realistic conditions, CAHPS ratings could affect consumer selection of health plans and ultimately contain costs. Other studies are needed to learn how to enhance exposure and use of CAHPS information in the real world as well as to identify other conditions in which CAHPS ratings could make a difference.

Adolescent↗
PubMed1999

In vivo ATP synthesis rates in single human muscles during high intensity exercise.

1. In vivo ATP synthesis rates were measured in the human medial gastrocnemius muscle during high intensity exercise using localized 31P-magnetic resonance spectroscopy (31P-MRS). Six-second localized spectra were acquired during and following a 30 s maximal voluntary rate exercise using a magnetic resonance image-guided spectral localization technique. 2. During 30 s maximal voluntary rate exercise, ATPase fluxes were predominantly met by anaerobic ATP sources. Maximal in vivo glycogenolytic rates of 207 +/- 48 mM ATP min-1 were obtained within 15 s, decreasing to 72 +/- 34 mM ATP min-1 by the end of 30 s. In contrast, aerobic ATP synthesis rates achieved 85 +/- 2 % of their maximal capacity within 9 s and did not change throughout the exercise. The ratio of peak glycolytic ATP synthesis rate to maximal oxidative ATP synthesis was 2.9 +/- 0.9. 3. The non-Pi, non-CO2 buffer capacity was calculated to be 27.0 +/- 6. 2 slykes (millimoles acid added per unit change in pH). At the cessation of exercise, Pi, phosphomonoesters and CO2 were predicted to account for 17.2 +/- 1.5, 5.57 +/- 0.97 and 2.24 +/- 0.34 slykes of the total buffer capacity. 4. Over the approximately linear range of intracellular pH recovery following the post-exercise acidification, pHi recovered at a rate of 0.19 +/- 0.03 pH units min-1. Proton transport capacity was determined to be 16.4 +/- 4.1 mM (pH unit)-1 min-1 and corresponded to a maximal proton efflux rate of 15.3 +/- 2.7 mM min-1. 5. These data support the observation that glycogenolytic and glycolytic rates are elevated in vivo in the presence of elevated Pi levels. The data do not support the hypothesis that glycogenolysis follows Michealis-Menten kinetics with an apparent Km for [Pi] in vivo. 6. In vivo -measured ATP utilization rates and the initial dependence on PCr and glycolysis were similar to those previously reported in in situ studies involving short duration, high intensity exercise. This experimental approach presents a non-invasive, quantitative measure of peak glycolytic rates in human skeletal muscle.

Adenosine Triphosphate↗
PubMed1999

Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections.

The efficacy and safety of zanamivir, administered 2x or 4x daily over 5 days, was evaluated in the treatment of influenza infections. A total of 1256 patients entered the study; 57% of those randomized had laboratory-confirmed influenza infection. The primary end point, "alleviation of major symptoms," was created to evaluate differences in clinical impact. In the overall population with or without influenza infection, zanamivir reduced the median number of days to reach this end point by 1 day (P=.012 2x daily vs. placebo; P=.014 4x daily vs. placebo). The reduction was greater in patients treated within 30 h of symptom onset, febrile at study entry, and in defined high-risk groups. Zanamivir reduced nights of disturbed sleep, time to resumption of normal activities, and use of symptom relief medications. It was well tolerated. These results suggest that zanamivir can significantly reduce the duration and overall symptomatic effect of influenza.

Adult↗
PubMed1999

Conditional stability of the HemA protein (glutamyl-tRNA reductase) regulates heme biosynthesis in Salmonella typhimurium.

In many bacteria, including the enteric species Salmonella typhimurium and Escherichia coli, heme is synthesized starting from glutamate by a pathway in which the first committed step is catalyzed by the hemA gene product, glutamyl-tRNA reductase (HemA). We have demonstrated previously that when heme limitation is imposed on cultures of S. typhimurium, HemA enzyme activity is increased 10- to 25-fold. Western (immunoblot) analysis with monoclonal antibodies reactive with HemA revealed that heme limitation results in a corresponding increase in the abundance of the enzyme. Similar regulation was also observed for E. coli. The near absence of regulation of hemA-lac operon fusions suggested a posttranscriptional control. We report here the results of pulse-labeling and immunoprecipitation studies of this regulation. The principal mechanism that contributes to elevated HemA abundance is protein stabilization. The half-life of HemA protein is approximately 20 min in unrestricted cells but increases to >300 min in heme-limited cells. Similar regulation was observed for a HemA-LacZ hybrid protein containing almost all of the HemA protein (416 residues). Sodium azide prevents HemA turnover in vivo, suggesting a role for energy-dependent proteolysis. This was confirmed by the finding that HemA turnover is completely blocked in a lon clpP double mutant of E. coli. Each single mutant shows only a small effect. The ClpA chaperone, but not ClpX, is required for ClpP-dependent HemA turnover. A hybrid HemA-LacZ protein containing just 18 amino acids from HemA is also stabilized in the lon clpP double mutant, but this shorter fusion protein is not correctly regulated by heme limitation. We suggest that the 18 N-terminal amino acids of HemA may constitute a degradation tag, whose function is conditional and modified by the remainder of the protein in a heme-dependent way. Several models are discussed to explain why the turnover of HemA is promoted by Lon-ClpAP proteolysis only when sufficient heme is available.

ATP-Dependent Proteases↗
PubMed1999

Zanamivir: a review of clinical safety.

Preclinical and clinical studies have clearly demonstrated that zanamivir, a potent and highly selective inhibitor of the influenza A and B virus neuraminidase, has an impressive safety profile. This report describes the safety and tolerability findings from the clinical studies completed up to the 17 July 1998 involving over 6000 adult and adolescent patients from North America, Europe and the Southern Hemisphere. Serious adverse events from an ongoing Japanese clinical programme are also reported. Zanamivir was administered in various dose forms and frequencies and was found to have a comparable safety profile with placebo when given for both the treatment and prophylaxis of influenza-like illness. These findings were independent of age and underlying medical condition. 4152 patients received zanamivir and the most commonly reported adverse events were consistent with the signs and symptoms of influenza-like illness. Most of the adverse events were mild and did not result in patient withdrawal from the studies. Less than 1% of zanamivir and placebo recipients reported a serious adverse event. In addition, 490 healthy volunteers received zanamivir in clinical pharmacology studies. It was well tolerated and the incidence of adverse events was similar in zanamivir and placebo recipients. In addition, no clinically significant laboratory abnormalities were detected. Results from in vitro and in vivo animal studies suggest that zanamivir has low acute toxicity and no significant systemic toxicity or respiratory tract irritancy at plasma exposures more than 100-fold higher than those anticipated following clinical use. Neither genotoxic nor reproductive types of toxicity have been observed in toxicology studies at doses equal to 17 to 197 times the current therapeutic dose (20 mg/day). The characteristics of the molecule and the low systemic exposure indicate a very low potential for drug interactions with the inhaled route. Furthermore, repeated 600mg intravenous doses were well tolerated in healthy volunteers. The observed safety profile of zanamivir compares favourably with currently available agents with anti-influenza virus activity, such as rimantadine and amantadine, as well as GS4104, a neuraminidase inhibitor currently in phase III development. This may be attributed to the low systemic bioavailability of zanamivir, which is given by oral inhalation, direct to the primary site of viral replication. The potential advantages of this include a reduced risk of drug-drug interactions, other nontarget organ toxicities (e.g. brain) and drug clearance issues from both kidney and liver. Therefore, the safety profile of zanamivir supports its use in the management of influenza.

Animals↗
PubMed1998

Fate of subpulmonary homograft conduits: determinants of late homograft failure.

PATIENTS AND METHODS: Between 1971 and 1993, 656 conduits were placed in the subpulmonary position. Patients receiving heterografts or valveless conduits and patients dying within 90 days of insertion were excluded; thus 405 homograft conduits were studied. There were 293 aortic homografts, 94 pulmonary, and 18 of unknown type. The end point of conduit failure was defined by conduit replacement for whatever reason, balloon dilation of the conduit, or death of the patient with the conduit in place. The following factors were analyzed: aortic versus pulmonary homograft, antibiotic preservation versus cryopreservation, ABO and Rh compatibility, type of material used for conduit extension, age at operation, size of the conduit, diagnosis, and reoperations. Conduit number (1 to 405) in the series was included in the multivariable model. RESULTS: First conduits and conduits inserted earlier in the series appeared to last longer than second and subsequent conduits and those inserted later in the series (p = 0.001 and 0.003, respectively). Overall survival of conduits at 5, 10, and 15 years was 84% (95% CL, 80% to 88%), 58% (95% CL, 50% to 66%), and 31% (95% CL, 19% to 43%). Corresponding figures for the first conduits were 88% (95% CL, 84% to 92%), 65% (95% CL, 56% to 73%), and 34% (95% CL, 20% to 47%). The longest surviving homograft conduit in our series lasted 22.7 years. Regarded univariately, reoperation (redo worse), order number (recent worse), type of conduit (pulmonary worse than aortic), preservation (cryopreserved worse than antibiotic preserved), and age at operation (older patients worse) were statistically significant. However, in multivariable analysis, including all the above in the model, only reoperation and order number had significant predictive power. When patient survival was considered, patients operated on more recently survived longer despite the fact that their conduits were being replaced earlier. Overall, survival of patients at 5 and 15 years was 95% (95% CL, 93% to 98%) and 85% (95% CL, 77% to 92%), respectively. CONCLUSIONS: Pulmonary and aortic homografts, both cryopreserved and preserved in nutrient antibiotic solution, give similar results. All conduits will probably have to be replaced during the lifetime of the patient. In view of the worse performance of replacement conduits, techniques of repair that avoid the use of conduits should be further explored. Despite gradual deterioration of homograft conduits, they remain an important tool in the correction of many complex lesions with excellent 15-year patient survival.

Adolescent↗
PubMed1998

Early age at repair prevents restrictive right ventricular (RV) physiology after surgery for tetralogy of Fallot (TOF): diastolic RV function after TOF repair in infancy.

OBJECTIVES: To assess diastolic right ventricular (RV) physiology after tetralogy of Fallot repair in infancy. BACKGROUND: Restrictive RV physiology after tetralogy of Fallot repair is related to type of repair, pulmonary regurgitation, and late arrhythmias. METHODS: Forty-seven patients were investigated, 27 and 20 patients in Lund and London, respectively. Median age at repair was 0.78 years (0.08-0.99) and median follow-up was 3.0 years (0.08-10.4). Restrictive RV physiology was assessed by Doppler echocardiography. RESULTS: Thirteen patients (28%) had restrictive RV physiology at follow-up, three of 19 patients (16%) with transatrial repair and 10 of 28 patients (32%) with transventricular repair, respectively (p=0.1). Ten percent of the patients repaired before 6 months of age were restrictive at follow-up, increasing to 38% with repair after 9 months. Transannular patch (TAP) repair was performed in 55% of the patients, including eight of 10 patients (80%) with repair before 6 months of age. Thirty-one percent of the patients with TAP repair were restrictive. These restrictive patients had more severe preoperative pulmonary stenosis (p < 0.05), were older at repair (p < 0.05), and had shorter duration of pulmonary regurgitation (p < 0.001) at follow-up. CONCLUSIONS: Restrictive RV physiology is inversely related to age at repair and independent of type of outflow tract repair. Since TAP repair is more common in early repair, and restriction seems to be less frequent, long-term follow-up to assess adverse effects of pulmonary regurgitation is mandatory.

Age Factors↗
PubMed1998

Cost comparison between bilateral simultaneous, staged, and unilateral total joint arthroplasty.

A hospital-based computer system was used to compare the inpatient costs of performing bilateral simultaneous sequential, staged, and unilateral total hip and knee arthroplasties. Bilateral simultaneous sequential total knee arthroplasty was 36% less costly than 2 unilateral total knee arthroplasties. Bilateral simultaneous sequential total hip arthroplasty saved 25% over the costs of performing 2 unilateral hip arthroplasties. Prosthetic costs range between 28% and 43% of the total costs of hospitalization. There was a significant correlation between hospital length of stay, morbidity, and total costs, but no correlation with patient age and sex except in the unilateral knee patients. Bilateral simultaneous sequential joint arthroplasty can save more than $10,000 for each total knee patient and more than $8,000 for each total hip patient.

Adult↗
PubMed1998

Analysis of the repeatability of tear break-up time measurement techniques on asymptomatic subjects before, during and after contact lens wear.

This study assessed the repeatability of various methods of measuring tear break-up time (TBUT) with and without soft contact lenses (CLs). TBUT was measured on 22 subjects with the tearscope, videokeratoscope and slit-lamp before and after 30 min of soft CL wear, and immediately after CL removal. Slit-lamp corneal TBUT was measured with fluorescein and without fluorescein while wearing CLs. TBUT was measured three times on the right eye only, using each technique in randomised order. TBUT measurements on CLs were repeated a second day. TBUT measurements were highly variable under all conditions and our results indicated a lack of correlation between techniques. The videokeratoscope was the least repeatable; while the tearscope was the most repeatable technique.

Journal Article↗
PubMed1998

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Clinical Competence↗