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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 19 recordsLinked to original sources

Clinical classification criteria for knee osteoarthritis: performance in the general population and primary care.

BACKGROUND: Doubts have been expressed about the performance of the American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis when applied in the general population. OBJECTIVE: To investigate whether the distribution of population subgroups and underlying disease severity might explain the performance of these criteria in the population setting. METHODS: Population-based cross-sectional study. 819 adults aged > or = 50 years reporting knee pain in the last 12 months were clinically assessed by research therapists using standardised protocols and blinded to radiographic status. All participants underwent plain radiography of the knees, scored by a single reader blinded to clinical status. The relationship between fulfilling the ACR clinical classification criteria for knee osteoarthritis and the presence of symptomatic radiographic knee osteoarthritis was summarised for the sample as a whole and within subgroups. RESULTS: Radiographic osteoarthritis was present in 539 participants (68%) and symptomatic radiographic knee osteoarthritis in 259 (33%). 238 participants (30%) fulfilled the ACR clinical criteria for knee osteoarthritis. Agreement between the ACR clinical criteria and symptomatic radiographic knee osteoarthritis was low (sensitivity 41%; specificity 75%; positive predictive value 44%; negative predictive value 72%). Sensitivity and specificity did not vary markedly between population subgroups, although they were influenced by the underlying severity of radiographic osteoarthritis. CONCLUSION: The ACR clinical criteria seem to reflect later signs in advanced disease. Other approaches may be needed to identify early, mild osteoarthritis in the general population and primary care.

Aged↗

Clinical service organisation for heart failure.

BACKGROUND: Chronic heart failure (CHF) is a serious, common condition associated with frequent hospitalisation. Several different disease management interventions (clinical service organisation interventions) for patients with CHF have been proposed. OBJECTIVES: To assess the effectiveness of disease management interventions for patients with CHF. SEARCH STRATEGY: We searched: Cochrane CENTRAL Register of Controlled Trials (to June 2003); MEDLINE (January 1966 to July 2003); EMBASE (January 1980 to July 2003); CINAHL (January 1982 to July 2003); AMED (January 1985 to July 2003); Science Citation Index Expanded (searched January 1981 to March 2001); SIGLE (January 1980 to July 2003); DARE (July 2003); National Research Register (July 2003); NHS Economic Evaluations Database (March 2001); reference lists of articles and asked experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing disease management interventions specifically directed at patients with CHF to usual care. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data information and assessed study quality. Study authors were contacted for further information where necessary. MAIN RESULTS: Sixteen trials involving 1,627 people were included. We classified the interventions into three models: multidisciplinary interventions (a holistic approach bridging the gap between hospital admission and discharge home delivered by a team); case management interventions (intense monitoring of patients following discharge often involving telephone follow up and home visits); and clinic interventions (follow up in a CHF clinic). There was considerable overlap within these categories, however the components, intensity and duration of the interventions varied. Case management interventions tended to be associated with reduced all cause mortality but these findings were not statistically significant (odds ratio 0.86, 95% confidence interval 0.67 to 1.10, P = 0.23), although the evidence was stronger when analysis was limited to the better quality studies (odds ratio 0.68, 95% confidence interval 0.46 to 0.98, P = 0.04). There was weak evidence that case management interventions may be associated with a reduction in admissions for heart failure. It is unclear what the effective components of the case management interventions are. The single RCT of a multidisciplinary intervention showed reduced heart-failure related re-admissions in the short term. At present there is little available evidence to support clinic based interventions. AUTHORS' CONCLUSIONS: The data from this review are insufficient for forming recommendations. Further research should include adequately powered, multi-centre studies. Future studies should also investigate the effect of interventions on patients' and carers' quality of life, their satisfaction with the interventions and cost effectiveness.

Case Management↗

The impact of head injury neurobehavioural sequelae on personal relationships: preliminary findings.

BACKGROUND: Existing evidence suggests that neurobehavioural disability is a frequent legacy of serious head trauma and has a major impact on the psychological well-being of relatives and friends of people with brain injuries. OBJECTIVE: To explore which neurobehavioural legacies of serious head trauma have the greatest impact on personal relationships and increase the risk of relationship breakdown. METHOD: Forty-eight partners of people who had suffered serious head trauma were asked to complete a 12-item measure to rate how different neurobehavioural characteristics had adversely affected their relationship with the brain injured person. Twenty-three couples who had divorced or separated from their injured partner in the years following injury comprised the 'separated' group, 25 still in the relationship at the time data were collected comprised the 'together' group. RESULTS: Even though many neurobehavioural characteristics of brain injury were reported by partners of both the separated and the together group as placing a strain on the relationship only mood swings accounted for a significant between groups difference [t(40.13) = 3.33, p = 0.002]. The magnitude of the difference in the means was large (712 = 0.19). CONCLUSIONS: Unpredictable patterns of behaviour, as perceived by partners of brain injured individuals, impose the greatest burden on personal relationships and may contribute to relationship breakdown.

Adolescent↗

2-MeOE2bisMATE induces caspase-dependent apoptosis in CAL51 breast cancer cells and overcomes resistance to TRAIL via cooperative activation of caspases.

2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite which inhibits tubulin polymerisation and has anti-tumour and anti-angiogenic activity. 2-MeOE2 induces apoptosis in a wide range of cancer cell types and has recently been demonstrated to cooperate with TRAIL to induce apoptosis in breast cancer cells. 2-Methoxyoestradiol-3,17-bis-O,O-sulphamate (2-MeOE2bisMATE) is a sulfamoylated derivative of 2-MeOE2 with enhanced activity and improved pharmacokinetic properties, and 2-MeOE2bisMATE is a promising candidate for early clinical trials. It is important, therefore, to understand the mechanisms by which 2-MeOE2bisMATE acts, and whether it retains the ability to cooperate with TRAIL. We demonstrate that 2-MeOE2bisMATE-induced apoptosis of CAL51 breast cancer cells was associated with rapid activation of caspase 3 and 9, but not caspase 8 (as measured by BID cleavage) and was completely prevented by the caspase inhibitor zVADfmk. Interfering with Fas- or TRAIL-receptor function did not prevent 2-MeOE2bisMATE-induced apoptosis. Whereas CAL51 cells were resistant to TRAIL-induced apoptosis, 2-MeOE2bisMATE and TRAIL cooperated to induce cell death. This apoptosis was associated with enhanced activation of caspases, but not increased expression of the DR5 TRAIL receptor, previously demonstrated to be induced by 2-MeOE2. Therefore, 2-MeOE2bisMATE-induced apoptosis is dependent on caspases and like 2-MeOE2, 2-MeOE2bisMATE can overcome resistance to TRAIL by stimulating activation of downstream caspases. Our results suggest that 2-MeOE2bisMATE and TRAIL might be a particularly effective combination of anti-cancer agents.

2-Methoxyestradiol↗

Near-threshold production of the multistrange Xi- hyperon.

The yield for the multistrange Xi(-) hyperon has been measured in 6A GeV Au+Au collisions via reconstruction of its decay products pi(-) and Lambda, the latter also being reconstructed from its daughter tracks of pi(-) and p. The measurement is rather close to the threshold for Xi(-) production and therefore provides an important test of model predictions. The measured yield for Xi(-) and Lambda are compared for several centralities. In central collisions the Xi(-) yield is found to be in excellent agreement with statistical and transport model predictions, suggesting that multistrange hadron production approaches chemical equilibrium in high baryon density nuclear matter.

Journal Article↗

Comparison of source images for protons, pi-'s, and lambda's in 6A GeV Au+Au collisions.

Source images are extracted from two-particle correlations constructed from strange and nonstrange hadrons produced in 6A GeV Au+Au collisions. Very different source images result from pp vs p Lambda vs pi(-)pi(-) correlations. Scaling by transverse mass can describe the apparent source size ratio for p/pi(-) but not for Lambda/pi(-) or Lambda/p. These observations suggest important differences in the space-time emission histories for protons, pions, and neutral strange baryons produced in the same events.

Journal Article↗

The effects of smoking on birthweight-for-gestational-age curves in teenage and adult primigravidae.

OBJECTIVE: To compare the effect of smoking on the birthweight-for-gestational-age curves of teenage and adult primigravidae. METHODS: A retrospective analysis of the perinatal database at the Liverpool Women's Hospital for the years 1997-1999 for teenage and adult primigravidae. RESULTS: Records on 1157 primigravidae were available. There were no significant differences between the mean birthweight (3220 g +/- 666 vs 3244 g +/- 680, P = 0.43) and the proportion with low birthweight (LBW) babies (8.9% vs 10.6%, P = 0.39) between teenage and adult primigravidae, respectively. The percentage of women who smoked increased from the middle class (Townsend score -6- - 3) to the working class group (Townsend score +4- + 12) for both teenagers (33.3-51.3%) and adults (6.9-29.6%). The mean birthweight of babies of smoking mothers was significantly lower than for non-smoking mothers (3112 g +/- 639 vs 3327 g +/- 663, P = 0.00002). The birthweight-for-gestational-age pattern was lower at all gestational ages for smoking mothers in both the teenage and adult groups. Risk of LBW was significantly increased in teenagers who smoked (10.8% vs 3.9%, P < 0.01), but not in adult smokers. CONCLUSION: Lower birthweights at all gestational ages were observed in babies of teenage and adult mothers who smoked.

Adolescent↗

Reproducibility of the blood lactate threshold, 4 mmol.l(-1) marker, heart rate and ratings of perceived exertion during incremental treadmill exercise in humans.

The aim of this study was to investigate the reproducibility of blood lactate measurements, heart rate (HR) and ratings of perceived exertion (RPE) during treadmill exercise at speeds corresponding to the lactate threshold ( v(Th,la)-) and a fixed blood lactate concentration of 4 mmol.l(-1)( v(la)-(,4)). Possible differences in reproducibility related to fitness levels were also investigated. A group of 20 men [mean (SD)] [age 20.5 (1.4) years] and 16 women [age 21.2 (0.9) years] took part in the study. The subjects performed two identical incremental exercise tests consisting of at least six 4 min stages. Blood lactate concentrations, HR and RPE were recorded at the end of each stage. Limits of agreement (LoA), correlation coefficients and 95% confidence intervals for the mean difference between tests were employed to investigate the level of agreement and reproducibility of blood lactate concentration, HR and RPE. For the group as a whole, the sample correlation coefficient for speed at v(Th,la)- was r=0.88, and was r=0.92 for the speed at v(la)-(,4). At v(Th,la) -, the correlation coefficients for the moderately fit and unfit were r=0.94 and r=0.36, respectively, and at v(la)-(,4) r=0.93 and r=0.68, respectively. The LoA for the moderately fit group indicated that a change of 1.62 km.h(-1) in v(Th,la)- would be necessary to be considered a change in training status. For HR and RPE, relationships between the tests were generally poor. The LoA suggested that changes in scores must be unacceptably large. These findings cast doubt on the sensitivity of testing for change of blood lactate concentration, HR and RPE in this population.

Adult↗

Longitudinal flow of protons from (2-8)A GeV central Au+Au collisions.

Rapidity distributions of protons from central 197Au+197Au collisions measured by the E895 Collaboration in the energy range from (2-8)A GeV at the Brookhaven AGS are presented. Longitudinal flow parameters derived using a thermal model including collective longitudinal expansion are extracted from these distributions. The results show an approximately linear increase in the longitudinal flow velocity, (L), as a function of the logarithm of beam energy.

Journal Article↗

Breast-feeding knowledge and attitudes of teenage mothers in Liverpool.

OBJECTIVES: To determine the knowledge and attitudes of teenage mothers towards breast-feeding. DESIGN: A questionnaire of teenage (< 20 years) and non-teenage (> or = 20 years) primigravidae attending the antenatal care services at the Liverpool Women's Hospital, during the period April-May 2000. RESULTS: Forty teenage primigravidae and 40 non-teenage primigravidae registered for the survey. Teenagers had poorer knowledge about breast-feeding than the non-teenagers, and fewer teenagers considered breast milk the best food for their baby. More teenagers than non-teenagers planned to bottle feed [23 (57.5%) vs. 9 (22.5%), P=0.002]. Only one teenager had knowledge about colostrum. Teenagers were more often single, had a lower level of education, higher unemployment, higher smoking frequency and less contact with a person who had previously breast-fed. CONCLUSION: Teenage primigravidae have poor knowledge regarding breast-feeding compared with non-teenage primigravidae. A greater proportion of teenagers opted not to breast-feed compared with non-teenagers. Health education classes stressing the importance of breast-feeding should be emphasized in antenatal teenage clinics. More research is needed to understand how to improve the knowledge and motivation of adolescent girls to breast feed.

Adolescent↗

Calibration of the Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) standard for human coagulation factor VIII concentrate for use in the potency assay.

The European Pharmacopoeia Biological Reference Preparation Batch 3/Mega 2 (United States/Food and Drug Administration) (Ph. Eur. BRP Batch 3/Mega 2 (US/FDA)) was developed as an internationally available, common working standard to replace the dwindling stocks of Mega 1 (the current US standard) and Ph. Eur. BRP Batch 2 (the current European standard). The potency was assigned in an international collaborative study with reference to four currently established standards, Ph. Eur. BRP batch 2, WHO 5th and 6th International Standard and Mega 1. Thirty-eight laboratories participated in the collaborative study. Each laboratory was asked to perform four independent assays. Participants used either the one stage clotting assay or the chromogenic assay or both. This publication reports the results obtained with both assays. The summary and conclusion, however highlight the results mainly with respect to the chromogenic assay, which is the assay prescribed in the European Pharmacopoeia. Data were analysed for both assays separately. A consensus potency value was calculated as the unweighted average of mean potencies determined against the four standards. A potency of 8.6 IU/vial as determined in the chromogenic substrate method was assigned to the candidate standard. Inter-laboratory agreement as assessed by calculation of the geometric coefficient of variation was below 10% for mean potencies against all four calibrators for the chromogenic assay. Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) is a freeze-dried, plasma derived, high-purity concentrate. The material was filled into approximately 100,000 vials and lyophilised to a final residual moisture of < or = 2%. Approximately 90,000 vials of the standard are available, equally shared between the two co-ordinating centers. Based on the stability studies, the predicted mean percentage loss per year at -20 degrees C is 0.000% and thus the candidate standard appears to be stable. The Ph. Eur. BRP batch 3 was adopted by the European Pharmacopoeia Commission in November 2001.

Blood Coagulation Tests↗

Model-independent source imaging using two-pion correlations in (2 to 8)a GeV Au+Au collisions.

We report a particle source imaging analysis based on two-pion correlations in high multiplicity Au+Au collisions at beam energies between 2A and 8A GeV. We apply the imaging technique introduced by Brown and Danielewicz, which allows a model-independent extraction of source functions with useful accuracy out to relative pion separations of about 20 fm. The extracted source functions have Gaussian shapes. Values of source functions at zero separation are almost constant across the energy range under study. Imaging results are found to be consistent with conventional source parameters obtained from a multidimensional Hanburg-Brown-Twiss analysis.

Journal Article↗

Directed flow of lambda hyperons in (2-6 )A GeV Au+Au collisions.

Directed flow measurements for Lambda hyperons are presented and compared to those for protons produced in the same Au+Au collisions (2A, 4A, and 6A GeV; b<5-6 fm). The measurements indicate that Lambda hyperons flow consistently in the same direction but with smaller magnitudes. A strong positive flow [for Lambdas] has been predicted in calculations which include the influence of the Lambda-nucleon potential. The experimental flow ratio Lambda/p is in qualitative agreement with expectations (approximately 2/3) from the quark counting rule at 2A GeV but is found to decrease with increasing beam energy.

Journal Article↗

Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)-encoded fusion proteins.

AML-1 is one of the most frequently translocated genes in human leukemia. AML-1 binds DNA and activates or represses transcription, while the chromosomal translocation fusion proteins in acute myeloid leukemia subvert these functions. The t(8;21) is the second most frequent translocation in acute myeloid leukemia and creates a fusion between the DNA binding domain of AML-1 and the ETO (also known as MTG8) corepressor. The t(12;21) is found in up to 25% of pediatric B cell acute lymphoblastic leukemias and fuses the ETS family transcription factor TEL to the amino terminus of AML-1. In addition, the inv(16), the most frequent translocation in acute myeloid leukemia, fuses the AML-1 cofactor CBFbeta to the smooth muscle myosin heavy chain MYH11. Both the t(8;21) and t(12;21) create transcriptional repressors that impair AML-1 target gene expression. We demonstrated that the fusion proteins encoded by these translocations contact the nuclear hormone corepressors (N-CoR/SMRT), mSin3A, and histone deacetylases. We have also found that both TEL and AML-1 interact with mSin3A. TEL also binds N-CoR and histone deacetylase-3, indicating that wild-type TEL is a transcriptional repressor. The t(12;21) fuses the mSin3A interaction domain of TEL to AML-1 to transform AML-1 from a regulated to an unregulated transcriptional repressor. The recognition that AML-1 interacts with mSin3A to repress transcription suggested that the inv(16) fusion protein might also repress the transcription of AML-1-target genes. In fact, the inv(16) encodes a protein that cooperates with AML-1 to repress transcription. The inv(16) fusion protein was found in a ternary complex with AML-1 and mSin3A, suggesting that the inv(16) also acts by recruiting transcriptional corepressors and histone deacetylases.

3T3 Cells↗

Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma.

PURPOSE: A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. METHODS: Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. RESULTS: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate. CONCLUSIONS: The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.

Adult↗

The effect of exercise on gait and balance in patients with chronic fatigue syndrome.

This study investigated anecdotal reports of gait and balance abnormalities in subjects with Chronic Fatigue Syndrome (CFS) by examining the effects of a light exercise test on postural sway and various gait parameters. Tests were performed on 11 CFS patients and 11 age- and sex-matched sedentary controls. Results demonstrated that postural sway was not significantly different in both groups before or after the exercise test. There were, however, significant differences in gait parameters between the two groups confirming anecdotal evidence, but these differences were not exacerbated by the exercise test. Heart rate responses demonstrated that both groups were exercising at similar loads, although this was perceived to be higher by the CFS group.

Adult↗