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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 37 records · Page 2Linked to original sources

Orthopaedic intervention in early rheumatoid arthritis. Occurrence and predictive factors in an inception cohort of 1064 patients followed for 5 years.

OBJECTIVES: To assess the occurrence of and predictive factors for orthopaedic surgery in an inception cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 5 yr in nine regions in England. METHODS: Standard clinical, laboratory and radiological assessments and all interventions were recorded at baseline and yearly in RA patients (less than 2 yrs symptoms) prior to the use of disease-modifying drugs. RESULTS: One thousand and sixty-four patients completed 5 yr of follow-up. Two hundred and sixty-four orthopaedic procedures for RA were performed in 181 (17%) patients at a median of 36.5 months from baseline. Seventy-five (7%) had replacements of major joints. Risk factors at baseline for large joint replacement surgery were a low haemoglobin concentration [odds ratio scores (OR) 3.4, 95% confidence interval (CI) 2.1-5.8] and high scores for erythrocyte sedimentation rate (ESR) (OR 3.2, CI 1.8-5.3), disease activity (DAS) (OR 2.1, CI 1.2-3.5) and Larsen X-rays (OR 2.6, CI 1.4-4.8). For hand or foot joint surgery (4%), risk factors included female gender (OR 3.2, CI 1.3-7.6), joint score (OR 2.3, CI 1.2-4.3), erosions (OR 2.3, CI 1.1-4.8), DAS (OR 2.4, 1.3-4.5) and Health Assessment Questionnaire score (OR 1.9, CI 1.0-3.6). No significant associations were seen for tendon, soft tissue or other minor procedures (6%). The HLA-DRB1 RA shared epitope was associated with any type of orthopaedic surgery (OR 1.7, CI 1.1-2.7). CONCLUSIONS: Eleven per cent of RA patients treated with conventional drug therapy for 5 yr underwent large- or small-joint surgery, an outcome which could be compared against that for new disease-modifying drugs. Risk factors varied according to type of surgery, but included standard clinical and laboratory measures. In order to reduce the eventual need for surgery, a therapeutic target in the first year of RA is the suppression of disease activity, as measured by haemoglobin and ESR. These are useful details for clinicians, health professionals and patients.

Adult↗

Physical fitness training for stroke patients.

BACKGROUND: Stroke patients have impaired physical fitness and this may exacerbate their disability. It is not known whether improving physical fitness after stroke reduces disability. OBJECTIVES: The primary aims of the review were to establish whether physical fitness training reduces death, dependence and disability after stroke. The secondary aims of the review included an investigation of the effects of fitness training on secondary outcome measures (including, physical fitness, mobility, physical function, health and quality of life, mood and the incidence of adverse events). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (June 2003). In addition, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2002 Issue 4), MEDLINE (1966 to December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002), SPORTDiscus (1949 to December 2002), Science Citation Index Expanded (1981 to December 2002), Web of Science Proceedings (1982 to December 2002), Physiotherapy Evidence Database (December 2002), REHABDATA (1956 to December 2002) and Index to UK Theses (1970 to December 2002). We hand searched relevant journals and conference proceedings and screened reference lists. To identify unpublished and ongoing trials we searched trials directories and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials were included when an intervention represented a clear attempt to improve either muscle strength and/or cardiorespiratory fitness, and whose control groups comprised either usual care or a non-exercise intervention. DATA COLLECTION AND ANALYSIS: Data from eligible studies were independently extracted by two reviewers. The primary outcome measures were death, disability and dependence. The lack of common outcome measures prevented some of the intended analysis. MAIN RESULTS: A total of twelve trials were included in the review. No trials reported death and dependence data. Two small trials reporting disability showed no evidence of benefit. The remaining available secondary outcome data suggest that cardiorespiratory training improves walking ability (mobility). Observed benefits appear to be associated with specific or 'task-related' training. REVIEWER'S CONCLUSIONS: There are few data available to guide clinical practice at present with regard to fitness training interventions after stroke. More general research is needed to explore the efficacy and feasibility of training, particularly soon after stroke. In addition more specific studies are required to explore the effect of content and type of training. Further research will require careful planning to address a number of issues peculiar to this type of intervention.

Exercise Therapy↗

Work-related tetraplegia: cause of injury and annual medical costs.

STUDY DESIGN: Descriptive study. OBJECTIVE: To describe the demographics, cause of injury, and annual-paid medical costs for the 5 years following injury for cases of work-related tetraplegia. SETTING: A single United States workers' compensation (WC) claims database. METHODS: Tetraplegia cases with initial date of injury from 1 January 1989 to 31 December 1999 were selected by cross-referencing word search terms pertaining to body part injured and nature of injury. The main outcome measures were injury causes and annual-paid medical payments (adjusted to year 2000 medical consumer price index) of work-related tetraplegia by injury group for each year postinjury over a 5-year time period. RESULTS: A total of 62 claimants with work-related tetraplegia injured between 1 January 1989 and 31 December 1999. The vast majority of those identified were male claimants (92%) and more than a quarter worked in the construction industry (26%). Other highly represented industries included transportation and retail (15% each), manufacturing (13%), and agriculture and utility (11% each). The majority of injuries were the result of falls (36%) and vehicular accidents (34%). The mean Year 1 cost was US dollars 560524 for those with a high-level tetraplegia (C2-4 ASIA A-C), US dollars 431033 for a low-level injury (C5-8 ASIA A-C), and US dollars 178041 for those with an ASIA D tetraplegia injury. The mean cost of subsequent years (Years 2-5) was US dollars 130992 for a high-level, US dollars 129250 for a low-level, and Us dollars 34352 for an ASIA D tetraplegia injury. CONCLUSIONS: Mean costs for Year 1 postinjury in WC cases are similar to previously published estimates. Comparing the current results with those of previous spinal cord injury cost studies suggests that those with work-related tetraplegia may receive more injury-related paid medical benefits after the first year postinjury than cases who do not receive WC-supported benefits. SPONSORSHIP: Supported, in part, by a grant from the National Institute on Disability and Rehabilitation Research (NIDDR) (Grant # H133N00024).

Accidents, Occupational↗

Insoluble zinc, cupric and tin pyrophosphates inhibit the formation of volatile sulphur compounds.

Oral malodour is mainly a result of the production of volatile sulphur compounds (VSC). The present study was concerned with investigating the anti-VSC effect of insoluble pyrophosphates (PP) of zinc, copper(II) and tin(II). The hypothesis to be tested was that the sulphide anions produced when VSC are solubilized in water have a higher affinity for the respective metal ions than the PP anion. The anti-VSC effects of insoluble PP were compared with the corresponding soluble metal salts using three in vitro methods: saliva putrefaction; dialysis of a suspension of PP and saliva against water; and analysis of water containing hydrogen sulphide and methyl mercaptan gases, and gases in the headspace. The levels of VSC were analysed by gas chromatography in the first and third methods, and released metal ions were analysed by atomic absorption spectroscopy in the second. The results showed that: the insoluble metal PP inhibited VSC formation in saliva by 99-100%; under dialysis, only minute amounts of metal ions are released from the combination of PP and saliva; and the PP lost their metal cations in water containing dissolved gases and inhibited VSC formation. Hence, the results support the experimental hypothesis. Sulphide ions are obviously very strong ligands for these metal ions.

Adult↗

A randomised controlled trial of occupational therapy for people with early rheumatoid arthritis.

BACKGROUND: Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function. OBJECTIVE: To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years). METHODS: A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES). RESULTS: Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39). CONCLUSIONS: OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base.

Adult↗

Stable transformation of Theobroma cacao L. and influence of matrix attachment regions on GFP expression.

We describe a protocol for Agrobacterium-mediated genetic transformation of Theobroma cacao L. using cotyledonary explants from primary somatic embryos (SEs) and A. tumefaciens strain AGL1. Transgenic plants carrying the visible marker, gene green fluorescent protein ( EGFP), the selectable marker gene neomycin phosphotransferase II ( NPTII), the class I chitinase gene from cacao ( Chi), and tobacco nuclear matrix attachment regions (MARs) in different combinations were successfully produced via regeneration of secondary SEs. The presence of the Chi gene or MARs did not influence the number of transgenic plants produced compared to the marker genes alone. However, the inclusion of MARs contributed to increased mean GFP expression in the population of transgenics. Additionally, the presence of MARs reduced the occurrence of gene silencing and stabilized high levels of GFP expression in lines of transgenic plants multiplied via reiterative somatic embryogenesis. Ninety-four transgenic plants were acclimated in a greenhouse and grown to maturity. Detailed growth analysis indicated that there were no differences in various growth parameters between transgenic and non-transgenic SE-derived plants. Seeds produced from two genetic crosses with one of the transgenic lines were analyzed for EGFP expression-a near-perfect 1:1 segregation was observed, indicating that this line resulted from the insertion of a single locus of T-DNA.

Base Sequence↗

Neuropeptide release influences brain edema formation after diffuse traumatic brain injury.

The mechanisms associated with edema formation after traumatic brain injury (TBI) have not been fully elucidated. In peripheral tissue injury, the neurogenic component of inflammation plays a significant role in increased vascular permeability and edema formation. However, few studies have examined the role of neuropeptide induced neurogenic inflammation following TBI. Adult male Sprague-Dawley rats were either left untreated, or pre-treated with capsaicin (125 mg/kg s.c.) or equal volume vehicle, and injured 14 days later using the 2-meter impact-acceleration model. Subgroups of animals were assessed for blood brain barrier (BBB) permeability (Evans Blue), brain edema (wet weight/dry weight) and functional outcome (Barnes maze and Rotarod) for up to 2 weeks post-trauma. Increased BBB permeability was present in untreated animals between 3 and 6 h after injury but not at later time-points. Edema was maximal at 5 h after trauma, declined and then significantly increased over the 5 days post-trauma. In contrast, capsaicin pre-treated, neuropeptide-depleted animals exhibited no significant increase in BBB permeability or edema compared to vehicle treated animals after injury. Notably, motor and cognitive impairments were significantly reduced in the capsaicin-pretreated animals. We conclude that neurogenic inflammation contributes to the development of edema and posttraumatic deficits after diffuse TBI.

Animals↗

Frailty and the biochemical effects of recombinant human growth hormone in women after surgery for hip fracture.

We report a randomised double blind controlled trial investigating the short-term biochemical and adverse clinical responses to recombinant human growth hormone (r-hGH) after surgery for hip fracture. Hip fractures are common, dangerous and expensive, typically affecting frail women with osteoporosis and reduced muscle mass and strength, factors also associated with poor clinical outcomes. Growth hormone therapy increases IGF-I levels, promotes anabolism and increases muscle strength in well older people and selected patient groups and therefore has therapeutic potential to assist recovery of frail patients.Thirty-one women, mean age 86 years, received 14 nightly subcutaneous injections of r-hGH 0.05 mg/kg/day (high dose) or 0.025 mg/kg/day (low dose), or placebo from the 4th post-operative day. There were several serious adverse clinical events but no excess number of adverse events in the r-hGH treatment groups. The r-hGH treatment groups had similar serum IGF-I and IGFBP-3 responses, both significantly different from placebo. The large inter-individual variation of IGF-I responses were inversely correlated with pre-treatment indicators of frailty (body composition and functional abilities).

Aged↗

The second generation of the International Equine Gene Mapping Workshop half-sibling linkage map.

A low-density, male-based linkage map was constructed as one of the objectives of the International Equine Gene Mapping Workshop. Here we report the second generation map based on testing 503 half-sibling offspring from 13 sire families for 344 informative markers using the CRIMAP program. The multipoint linkage analysis localized 310 markers (90%) with 257 markers being linearly ordered. The map included 34 linkage groups representing all 31 autosomes and spanning 2262 cM with an average interval between loci of 10.1 cM. This map is a milestone in that it is the first map with linkage groups assigned to each of the 31 automosomes and a single linkage group to all but three chromosomes.

Animals↗

Cancer-related fatigue--a difference of opinion? Results of a multicentre survey of healthcare professionals, patients and caregivers.

UNLABELLED: The objective of this study was to investigate the perceptions of patients with cancer, their caregivers and healthcare professionals (HCPs) about fatigue and its impact on quality of life. It was a cross-sectional survey, the respondents were patients with cancer attending three UK regional cancer centres (n = 1,370), their informal caregivers (n = 1,370) and a random selection of HCPs (oncologists/nurses/radiographers/haematologists; n = 1,098). The response rates for patients, caregivers and HCPs were 42%, 33% and 34% respectively. Fatigue was reported to affect 56% of patients and to have a considerable impact on quality of life. Caregivers also recognized that fatigue was a common problem, with significant effects on patients' quality of life and impact on themselves. Healthcare professionals recognized that fatigue was a common problem for their patients but overestimated its impact on some aspects of patients' daily lives. Although most HCPs reported that they prescribed/recommended treatment for over half of their patients, only 14% of patients reported receiving any such treatment. The most common advice was to take more rest and relaxation. CONCLUSIONS: patients with cancer report that fatigue is a common and distressing symptom and the importance of this symptom is generally recognized by both HCPs and lay-carers. Healthcare professionals need more information about the effectiveness of existing interventions for cancer-related fatigue and further research is required to improve the current management of this debilitating symptom.

Attitude of Health Personnel↗

A pilot study of adjuvant intraperitoneal 5-fluorouracil using 4% icodextrin as a novel carrier solution.

AIM: This pilot study utilised the sustained intraperitoneal (i.p.) dwell properties of an iso-osmotic solution of 4% icodextrin to investigate the tolerability, toxicity and feasibility of home-based i.p. 5FU adjuvant chemotherapy following resective surgery for colorectal cancer. METHODS: Twenty eligible patients (Dukes' stage B and C with potentially curative resection) underwent perioperative Tenckhoff catheter placement. Ten (6 male, 4 female, aged 46-85; mean 67.5 years) received 5FU chemotherapy. After initial flushing and gradual increase in volumes of 4% icodextrin alone, patients received home-based i.p. 5FU (150-300 mg/m(2)/day given as equal doses at 12-hourly intervals) for 14 days, with a 14-day recovery period, for a maximum of 6 courses. Two incurable patients, treated on compassionate grounds, provided further safety data. RESULTS: Nine of the 10 patients became proficient in self-treatment with 5FU and two completed 6 courses. Frequent abdominal pain was the main dose-limiting toxicity of 5FU, causing withdrawal of three patients after a high (300 mg/m(2)/day) first course and one following a third course at lower doses. I.p. 5FU concentrations (mean>30000 ngml(-1)) were 1000 fold higher than systemic venous levels. Bacterial peritonitis led to two withdrawals but was not a frequent event (microbiologically confirmed incidence of 1 per 27 catheter-months). CONCLUSIONS: Home-based i.p. adjuvant chemotherapy is a feasible treatment option in patients with surgically resected colorectal carcinoma.

Adenocarcinoma↗

Extra-relational sex among Hispanic women and their condom-related behaviours and attitudes.

Limited data are available concerning sexual behaviour of Hispanic women. A total of 318 Hispanic women were surveyed concerning extra-relational sex and their condom-related attitudes. Fifteen per cent of the sample had a secondary sex partner (apart from the first partner) during the three months preceding the survey. Of these women, 77 and 53% used condoms with their secondary and primary partners, respectively. Among women in monogamous relationships, condom use was low (17%), and nearly two-thirds (61%) of those with a high-risk partner did not use condoms. The most common concerns about condom use among these Hispanic women were a reduction in pleasurable sensations and embarrassment associated with buying condoms. Women with concurrent partners as compared to those with a single partner felt more at risk for HIV and STDs, were less likely to believe condoms have side effects or are unacceptable to their male partners and were more able to use condoms in long-term relations. In conclusion, extra-relational sex among Hispanic women may be higher than previously reported, although more favourable attitudes to condom use are seen among women with concurrent than those with a single partner. HIV/STD programmes in the Hispanic community should tailor to the sexual behaviour of their participants.

Adult↗

The cost-effectiveness of infliximab (Remicade) in the treatment of rheumatoid arthritis in Sweden and the United Kingdom based on the ATTRACT study.

OBJECTIVE: The cost per quality-adjusted life-year (QALY) of infliximab (Remicade) treatment in rheumatoid arthritis (RA) was estimated on the basis of a clinical trial comparing infliximab plus methotrexate with methotrexate alone in 428 patients with advanced disease [Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT)]. METHODS: The effect of infliximab on disease progression and related costs and utilities was estimated using two disease progression models based on epidemiological cohorts followed for up to 15 yr in Sweden and the UK. The clinical trial data were used directly in the model and extrapolated to 10 yr using a cohort from the epidemiological studies matched for gender, age, time since onset of RA and disease severity. RESULTS: One to two years of treatment with infliximab treatment reduced direct and indirect resource consumption in both countries, thereby partly offsetting the treatment cost. In the base case, including both direct and indirect costs, the cost per QALY gained was SEK 32 000 (euro 3440) in Sweden and GBP 21 600 (euro 34 800) for 1 yr of treatment. The respective QALY gains were 0.248 and 0.298. With 2 yr of treatment, the costs per QALY gained were SEK 150 000 (euro 16 100) and GBP 29 900 (euro;48 200). CONCLUSIONS: Although 1-2 yr of treatment with infliximab will lead to savings in both direct and indirect costs, these will not offset the drug cost. However, the cost-effectiveness ratios remain within the usual range for treatments to be recommended for use.

Adult↗

Combined effect of zinc ions and cationic antibacterial agents on intraoral volatile sulphur compounds (VSC).

OBJECTIVE: Volatile sulphur compounds (VSC) are major components of oral malodour. As both zinc ions and cationic antibacterial agents inhibit the formation of oral VSC, this study aimed to determine whether these agents combined have synergistic anti-VSC actions. METHODS: Baseline oral VSC measurements of mouth air from 10 volunteers following cysteine rinsing (6mM, pH 7.2) were obtained using gas chromatography (GC). Subjects rinsed for 1 min with 10ml of the test solutions, 0.3% zinc acetate (Zn), 0.025% chlorhexidine (CHX), 0.025% cetyl pyridinium (CPC), and the combinations Zn+CHX and Zn+CPC. Cysteine rinses were repeated at 1h, 2h and 3h and VSC measurements recorded. Three subjects rinsed with the Zn+CHX combination and fasted for 9h, undergoing cysteine rinses and VSC measurements at 3h intervals. 10 microl of the test solutions were also added to 1ml aliquots of human whole saliva (n=8). Following incubation at 37 degrees C for 24h VSC levels in the saliva headspace were measured by GC. Inhibition of VSC formation and the fractional inhibitory index indicating synergy were calculated. RESULTS: Zn+CHX mouthrinse had a synergistic anti-VSC effect, and was effective for at least 9h. Zn+CPC mouthrinse was less effective. Both combinations showed a synergistic inhibiting effect in-vitro. CONCLUSIONS: Synergy between Zn and the antibacterial agents confirms different mechanisms of operation.

Adult↗

Dual dopamine D2 receptor and beta2-adrenoceptor agonists for the treatment of chronic obstructive pulmonary disease: the pre-clinical rationale.

This paper describes the rationale for the development of dual dopamine D2-receptor and beta2-adrenoceptor agonists as potential treatments for the symptoms of chronic obstructive pulmonary disease (COPD). The putative involvement of pulmonary sensory afferent nerves in mediating the key COPD symptoms of breathlessness, cough and excess sputum production is outlined and the hypothesis that activation of D2-receptors on such nerves would modulate their activity is developed. This premise was tested, in a range of animal models, using the first of a novel class of dual dopamine D2-receptor and beta2-adrenoceptor agonists, sibenadet HCl (Viozan, AR-C68397AA). In the course of these studies it was demonstrated that sibenadet, through activation of D2-receptors, inhibited discharge of rapidly adapting receptors and was effective in reducing reflex-induced tachypnoea, mucus production and cough in the dog. Sibenadet, through its activation of beta2-adrenoceptors, was also shown to be an effective bronchodilator with a prolonged duration of action following topical administration to the lungs. These studies also indicated that sibenadet had a wide therapeutic ratio with respect to expected undesirable side-effects such as emesis and cardiovascular disturbances. These results provided a compelling rationale for the initiation of a clinical development programme with sibenadet for the treatment of COPD.

Adrenergic beta-2 Receptor Agonists↗

Bloody diarrhoea: a rare presentation of a systemic disease.

Bloody diarrhoea in adolescents is usually due to enteric infection or inflammatory bowel disease. We describe a patient with bloody diarrhoea and endoscopic features of colitis in association with a systemic vasculitis. Positive anti-proteinase-3 antineutrophil cytoplasmic antibodies and cutaneous vasculitis on biopsy confirmed the diagnosis of Wegener's granulomatosis. He was started on high dose steroids and cyclophosphamide but required plasmapheresis for a declining renal function. The case highlights the need for vigilance with common clinical problems, because a life-threatening condition may be averted by prompt recognition and urgent therapy with immunosuppressants.

Adolescent↗

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗