A comparison of home and hospital-based exercise training in heart failure: immediate and long-term effects upon physical activity level.

BACKGROUND: In heart failure, reduced physical activity level can adversely affect physical and psychosocial functioning. No previous heart failure research has compared effects of home and hospital-based exercise training upon physical activity level, or has objectively assessed their long-term effects upon physical activity. This study used an activPAL™ monitor to examine immediate and long-term effects of home and hospital-based aerobic exercise training upon physical activity level. DESIGN: Randomized controlled trial. METHODS: Sixty patients with heart failure (mean age 66 years; NYHA class II/III; 51 male/9 female) were randomized to home training, hospital training or control. Both programmes consisted of aerobic circuit training, undertaken twice a week for one hour, for eight weeks. All participants wore the activPAL™ at baseline, and after eight weeks, for one week. Six months after cessation of training, a subgroup of participants from the home and hospital training groups (n = 10 from each group) wore the activPAL™ for a further week. RESULTS: Hospital-based training significantly increased steps taken per day during 'extra long' (P = 0.04) and 'long' (P = 0.01) walks. Neither programme had any immediate effect upon physical activity level otherwise. Though daily upright duration for the home group significantly improved six months after cessation of training (P = 0.02), generally physical activity level was maintained in the long term for both training groups. CONCLUSIONS: Hospital-based training enabled participants to walk for longer periods. It is clinically important that both training groups maintained physical activity level in the long term, given the potential for heart failure to worsen over this time period.

Dynamic subcellular localization of isoforms of the folate pathway enzyme serine hydroxymethyltransferase (SHMT) through the erythrocytic cycle of Plasmodium falciparum.

BACKGROUND: The folate pathway enzyme serine hydroxymethyltransferase (SHMT) converts serine to glycine and 5,10-methylenetetrahydrofolate and is essential for the acquisition of one-carbon units for subsequent transfer reactions. 5,10-methylenetetrahydrofolate is used by thymidylate synthase to convert dUMP to dTMP for DNA synthesis. In Plasmodium falciparum an enzymatically functional SHMT (PfSHMTc) and a related, apparently inactive isoform (PfSHMTm) are found, encoded by different genes. Here, patterns of localization of the two isoforms during the parasite erythrocytic cycle are investigated. METHODS: Polyclonal antibodies were raised to PfSHMTc and PfSHMTm, and, together with specific markers for the mitochondrion and apicoplast, were employed in quantitative confocal fluorescence microscopy of blood-stage parasites. RESULTS: As well as the expected cytoplasmic occupancy of PfSHMTc during all stages, localization into the mitochondrion and apicoplast occurred in a stage-specific manner. Although early trophozoites lacked visible organellar PfSHMTc, a significant percentage of parasites showed such fluorescence during the mid-to-late trophozoite and schizont stages. In the case of the mitochondrion, the majority of parasites in these stages at any given time showed no marked PfSHMTc fluorescence, suggesting that its occupancy of this organelle is of limited duration. PfSHMTm showed a distinctly more pronounced mitochondrial location through most of the erythrocytic cycle and GFP-tagging of its N-terminal region confirmed the predicted presence of a mitochondrial signal sequence. Within the apicoplast, a majority of mitotic schizonts showed a marked concentration of PfSHMTc, whose localization in this organelle was less restricted than for the mitochondrion and persisted from the late trophozoite to the post-mitotic stages. PfSHMTm showed a broadly similar distribution across the cycle, but with a distinctive punctate accumulation towards the ends of elongating apicoplasts. In very late post-mitotic schizonts, both PfSHMTc and PfSHMTm were concentrated in the central region of the parasite that becomes the residual body on erythrocyte lysis and merozoite release. CONCLUSIONS: Both PfSHMTc and PfSHMTm show dynamic, stage-dependent localization among the different compartments of the parasite and sequence analysis suggests they may also reversibly associate with each other, a factor that may be critical to folate cofactor function, given the apparent lack of enzymic activity of PfSHMTm.

Modelling the cardiovascular system for assessing the blood pressure curve.

A four compartment model of the cardiovascular system is developed. To allow for easy interpretation and to minimise the number of parameters, an effort was made to keep the model as simple as possible. Using a standard method (Matlab function fminsearch) to calculate the parameter values led to unacceptable run times or non-convergence. Consequently we developed an algorithm which first finds the most important model parameters and uses these as a basis for a four stage process which accurately determines all parameter values. This process is then applied to data from three ICU patients. Good agreement between the model and measured arterial pressure is demonstrated in all cases.

Reaction front formation in contaminant plumes.

The formation of successive fronts in contaminated groundwater plumes by subsoil bacterial action is a commonly accepted feature of their propagation, but it is not obviously clear from a mathematical standpoint quite how such fronts are formed or propagate. In this paper we show that these can be explained by combining classical reaction-diffusion theory involving just two reactants (oxidant and reductant), and a secondary reaction in which a reactant on one side of such a front is (re-)formed on the other side of the front via diffusion of its product across the front. We give approximate asymptotic solutions for the reactant profiles, and the propagation rate of the front.

Activity-monitor accuracy in measuring step number and cadence in community-dwelling older adults.

The primary purpose of this study was to investigate the accuracy of the activPAL physical activity monitor in measuring step number and cadence in older adults. Two pedometers (New-Lifestyles Digi-Walker SW-200 and New-Lifestyles NL2000) used in clinical practice to count steps were simultaneously evaluated. Observation was the criterion measure. Twenty-one participants (65-87 yr old) recruited from community-based exercise classes walked on a treadmill at 5 speeds (0.67, 0.90, 1.12, 1.33, and 1.56 m/s) and outdoors at 3 self-selected speeds (slow, normal, and fast). The absolute percentage error of the activPAL was <1% for all treadmill and outdoor conditions for measuring steps and cadence. With the exception of the slowest treadmill speed, the NL-2000 error was <2%. The SW-200 was the least accurate device, particularly at slower walking speeds. The activPAL monitor accurately recorded step number and cadence. Combined with its ability to identify primary postures, the activPAL might be a useful and versatile device for measuring activity in older adults.

Randomised controlled trial of electrical stimulation of the quadriceps after proximal femoral fracture.

BACKGROUND AND AIMS: Proximal femoral fracture is often associated with long-term residual disability. Quadriceps weakness may be a factor in poor outcome. This study aimed to determine whether training of the quadriceps using electrical stimulation (ES) increases leg extensor power and decreases disability in elderly subjects rehabilitating after fracture. METHODS: A single-blind randomized controlled trial of elderly postsurgical proximal femoral fracture patients, comparing 6 weeks of supplementary electrical stimulation of the quadriceps (15 patients) to usual physiotherapy alone (11 patients). The electrical stimulation on:off duty cycle was 7:23 seconds, with 36 cycles per session, given daily as an in-patient and twice weekly after discharge. The primary outcome measure was change in leg extensor power (Nottingham Power Rig). Functional mobility (Elderly Mobility Scale), disability (Barthel Index) and health status (Nottingham Health Profile) were also measured. RESULTS: There was no significant difference in change in leg extensor power, or any other outcome measure, in the ES group compared to usual care controls. Fractured leg extensor power increased by 10.9 (standard error of the mean 2.1) Watts at 6 weeks in the ES group compared to 15.3 (5.5) in the controls (mean adjusted difference -3.1, 95% CI -7.8, 1.6 Watts). Only 3 (20%) of the intervention patients tolerated sufficient stimulation intensity to produce repetitive knee extension, while 11 (73%) sustained palpable or visible contractions with no leg movement. CONCLUSION: A 6-week program of electrical stimulation of the quadriceps did not increase leg extensor power, or reduce disability, in elderly patients rehabilitating after surgical fixation of proximal femoral fracture. In many patients local discomfort limited the intensity of electrical stimulation that could be delivered.

An atypical orthologue of 6-pyruvoyltetrahydropterin synthase can provide the missing link in the folate biosynthesis pathway of malaria parasites.

Folate metabolism in malaria parasites is a long-standing, clinical target for chemotherapy and prophylaxis. However, despite determination of the complete genome sequence of the lethal species Plasmodium falciparum, the pathway of de novo folate biosynthesis remains incomplete, as no candidate gene for dihydroneopterin aldolase (DHNA) could be identified. This enzyme catalyses the third step in the well-characterized pathway of plants, bacteria, and those eukaryotic microorganisms capable of synthesizing their own folate. Utilizing bioinformatics searches based on both primary and higher protein structures, together with biochemical assays, we demonstrate that P. falciparum cell extracts lack detectable DHNA activity, but that the parasite possesses an unusual orthologue of 6-pyruvoyltetrahydropterin synthase (PTPS), which simultaneously gives rise to two products in comparable amounts, the predominant of which is 6-hydroxymethyl-7,8-dihydropterin, the substrate for the fourth step in folate biosynthesis (catalysed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase; PPPK). This can provide a bypass for the missing DHNA activity and thus a means of completing the biosynthetic pathway from GTP to dihydrofolate. Supported by site-directed mutagenesis experiments, we ascribe the novel catalytic activity of the malarial PTPS to a Cys to Glu change at its active site relative to all previously characterized PTPS molecules, including that of the human host.

Comprehensive geriatric assessment and home-based rehabilitation for elderly people with a history of recurrent non-elective hospital admissions.

OBJECTIVE: To determine whether a co-ordinated programme of geriatric assessment and multidisciplinary home-based rehabilitation reduces disability and prevents non-elective hospital readmission in high-risk elderly patients. DESIGN: Nested case-control study comparing usual post-discharge care versus usual care plus a comprehensive geriatric assessment and home-based rehabilitation service, comprising nursing, occupational therapy and physiotherapy with geriatric medical review. Patients were >or=65 years with >or=2 non-elective hospital admissions within the previous 12 months. Disability was assessed using the 100-point Barthel index and Nottingham extended activities of daily living (EADL) score. Non-elective hospital admissions were recorded over 1-year follow-up. RESULTS: We studied 84 patients; 56 receiving the new service were matched to 28 controls. Intervention subjects received a median of 19 h [interquartile range (IQR) (7,35)] rehabilitation over 19 [IQR (6,42)] domiciliary visits. At 3 months, there was improvement in median Barthel and Nottingham EADL scores in the intervention group of 3 and 2 points, respectively, compared with reductions in controls of 3 and 6 points (both P<0.001, changes in intervention group versus controls); similar differences persisted in survivors at 12 months. There was a non-significant trend for reduction in the proportion of patients with further non-elective hospital admission in the intervention group (36/56, 64%) compared with controls (21/28, 75%; OR 0.70, 95% CI 0.34, 1.46). CONCLUSIONS: A co-ordinated programme of geriatric assessment and multidisciplinary home-based rehabilitation reduced disability in elderly patients at high risk for non-elective hospital admission. Further research is required to determine whether this approach can reduce the need for hospital admission.

Falls risk following discharge from a geriatric day hospital.

OBJECTIVE: To assess the predictive validity of the Elderly Mobility Scale (EMS), Functional Reach (FR) and the Barthel Index (BI) in identifying recurrent fallers following discharge from a geriatric day hospital (GDH). SUBJECTS: Seventy-six GDH patients with identified mobility problems. METHODS: Each patient was assessed by an independent physiotherapist before and after a programme of physiotherapy using the EMS, FR and BI and a 'falls follow-up' assessment was performed after four months. RESULTS: Fifty-four per cent (29 out of 54) of patients had reduced mobility at follow-up. Twenty-five per cent (18 out of 71) of patients had two or more falls post discharge. Using logistic regression analysis for EMS, FR and BI at discharge, each of these variables individually was significantly associated with the risk of having two or more falls (p = 0.008, 0.017 and 0.031 respectively). A prognostic tree was developed for GDH patients identifying high-risk and low-risk groups. CONCLUSION: EMS, FR and BI were all significantly associated with GDH patients with mobility problems having two or more falls. A prognostic tree identified high- and low-risk groups of GDH patients and should now be tested prospectively.