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Biomedical subjects

J Keen

Publications and source records attributed to J Keen.

At least 19 recordsLinked to original sources
PubMed2006

Shoulder and elbow function 2 years following long head triceps interposition flap transfer for massive rotator cuff tear reconstruction.

INTRODUCTION: Patient outcomes were determined at a minimum of 2 years following massive rotator cuff tear ( > or = 5 cm(2)) reconstruction using a triceps brachii long head interposition flap. A physiotherapist at an independent clinic performed all measurements. PATIENTS AND METHODS: Of 24 total eligible patients, 19 completed pre-operative and follow-up UCLA Shoulder Scores and ASES Function Scores. Of these 19 patients, 14 who did not have co-morbidities that negatively impacted their ability to perform intense exercise underwent a comprehensive clinical examination of involved and uninvolved side shoulder and elbow active range of motion and strength (both isometric instrumented manual muscle testing and concentric isokinetic measurements). RESULTS: At 2 years following surgery, pre-operative UCLA Shoulder Scores improved from 10.6 +/- 3 to 27.4 +/- 5 and pre-operative ASES Function Scores improved from 20.1 +/- 10 to 43.2 +/- 5. However, isometric involved side shoulder abductor torque was decreased by 28.2% with instrumented manual muscle testing, and concentric shoulder external rotator torque was decreased by 44.6% at 60 degrees/s and by 53.8% at 120 degrees/s with isokinetic testing. Isometric involved side elbow extensor torque was decreased by 39% with instrumented manual muscle testing, and concentric elbow extensor torque was decreased by 17.7% and 19.2% at 60 and 120 degrees/s, respectively, with isokinetic testing. Including three additional patients who were contacted via telephone, the majority of patients (21 of 22, 95.4%) were satisfied with their improved shoulder function and reduced pain. CONCLUSIONS: Despite reduced pain and improved shoulder function, residual involved side shoulder abductor; shoulder external rotator and elbow extensor strength deficits were evident at 2 years following surgery. This suggests the need for more focused rehabilitation, particularly for involved side elbow extensor strengthening to further improve patient function and minimize disability.

Aged↗
PubMed2006

Systematic reviews of clinical decision tools for acute abdominal pain.

OBJECTIVES: To review for acute abdominal pain (AAP), the diagnostic accuracies of combining decision tools (DTs) and doctors aided by DTs compared with those of unaided doctors. Also to evaluate the impact of providing doctors with an AAP DT on patient outcomes, clinical decisions and actions, what factors are likely to determine the usage rates and usability of a DT and the associated costs and likely cost-effectiveness of these DTs in routine use in the UK. DESIGN: Electronic databases were searched up to 1 July 2003. REVIEW METHODS: Data from each eligible study were extracted. Potential sources of heterogeneity were extracted for both questions. For the accuracy review, meta-analysis was conducted. Among studies comparing diagnostic accuracies of DTs with unaided doctors, error rate ratios provided estimates of the differences between the false-negative and false-positive rates of the DT and unaided doctors' performance. Pooled error rate ratios and 95% confidence intervals (CIs) for false-negative rates and false-positive rates were computed. Metaregression was used to explore heterogeneity. RESULTS: Thirty-two studies from 27 articles, all based in secondary care, were eligible for the review of DT accuracies, while two were eligible for the review of the accuracy of hospital doctors aided by DTs. Sensitivities and specificities for DTs ranged from 53 to 99% and from 30 to 99%, respectively. Those for unaided doctors ranged from 64 to 93% and from 39 to 91%, respectively. Thirteen studies reported false-positive and false-negative rates for both DTs and unaided doctors, enabling a direct comparison of their performance. In random effects meta-analyses, DTs had significantly lower false-positive rates (error rate ratio 0.62, 95% CI 0.46 to 0.83) than unaided doctors. DTs may have higher false-negative rates than unaided doctors (error rate ratio 1.34, 95% CI 0.93 to 1.93). Significant heterogeneity was present. Two studies compared the diagnostic accuracies of doctors aided by DTs to unaided doctors. In a multiarm cluster randomised controlled trial (n = 5193), the diagnostic accuracy of doctors not given access to DTs was not significantly worse (sensitivity 28.4% and specificity 96.0%) than that of three groups of aided doctors (sensitivities of 42.4-47.9%, and specificities of 95.5-96.5%, respectively). In an uncontrolled before-and-after study (n = 1484), the sensitivities and specificities of aided and unaided doctors were 95.5% and 91.5% (p = 0.24) and 78.1% and 86.4% (p < 0.001), respectively. The metaregression of DTs showed that prospective test-set validation at the site of the tool's development was associated with considerably higher diagnostic accuracy than prospective test-set validation at an independent centre [relative diagnostic odds ratio (RDOR) 8.2; 95% CI 3.1 to 14.7]. It also showed that the earlier in the year the study was performed the higher the performance (RDOR 0.88, 0.83 to 0.92), that when developers evaluated their own DT there was better performance than when independent evaluators carried out the study (RDOR = 3.0, 1.3 to 6.8), and that there was no evidence of association between other quality indicators and DT accuracy. The one eligible study of the impact study review, a four-arm cluster randomised trial (n = 5193), showed that hospital admission rates of patients by doctors not allocated to a DT (42.8%) were significantly higher than those by doctors allocated to three combinations of decision support (34.2-38.5%) (p < 0.001). There was no evidence of a difference between perforation rates (p = 0.19) and negative laparotomy rates in the four trial arms (p = 0.46). Usage rates of DTs by doctors in accident and emergency departments ranged from 10 to 77% in the six studies that reported them. Possible determinants of usability include the reasoning method used, the number of items used and the output format. A deterministic cost-effectiveness comparison demonstrated that a paper checklist is likely to be 100-900 times more cost-effective than a computer-based DT, under stated assumptions. CONCLUSIONS: With their significantly greater specificity and lower false-positive rates than doctors, DTs are potentially useful in confirming a diagnosis of acute appendicitis, but not in ruling it out. The clinical use of well-designed, condition-specific paper or computer-based structured checklists is promising as a way to improve impact on patient outcomes, subject to further research.

Abdominal Pain↗
PubMed2001

Yin-Yang 1 activates interleukin-4 gene expression in T cells.

Interleukin-4 (IL-4) is a multifunctional cytokine that plays an important role in immune and inflammatory responses. Expression of the IL-4 gene is tightly controlled at the level of gene transcription by both positive and negative regulatory elements in the IL-4 promoter. Several constitutive nuclear factors have been identified that can interact with IL-4 promoter elements in DNA binding assays. Here we report that the zinc-finger protein YY-1 (Yin-Yang 1) can bind to multiple elements within the human IL-4 promoter. Cotransfection of Jurkat T cells with different IL-4 promoter/reporter constructs together with expression vectors encoding antisense, wild-type, or zinc finger-deleted mutant YY-1 suggested that YY-1 enhanced IL-4 promoter activity in a DNA-binding domain-dependent manner. Site-directed mutagenesis revealed that a proximal YY-1-binding site, termed Y0 ((-59)TCATTTT(-53)), was essential for YY-1-driven IL-4 promoter activity. In addition, cotransfected YY-1 enhanced both IL-4 promoter activity and endogenous IL-4 gene expression in nontransformed peripheral blood T cells. Thus, YY-1 positively regulates IL-4 gene expression in lymphocytes.

Calcimycin↗
PubMed2001

Residential rehabilitation for drug users: a review of 13 months' intake to a therapeutic community.

BACKGROUND: Residential rehabilitation based on 'therapeutic community' treatment for drug users is a treatment option which is attractive to GPs and others referring drug users for treatment. Whilst there is evidence that maintenance-based programmes for drug users are effective, there have been fewer attempts to evaluate the effectiveness of abstinence-based programmes which are relatively more intensive and expensive interventions. OBJECTIVE: This paper reports and evaluates the outcomes for 13 months' intake of 138 drug users to a residential community. METHODS: We carried out a retrospective cohort study using existing clinical and residential record data. The setting is a residential rehabilitation centre run by the charity Phoenix House in Sheffield, UK, offering a 1-year programme for heroin addicts including community detoxification overseen by primary care specialist doctors and residential rehabilitation. Participants were all patients who entered treatment between 1 February 1998 and 28 February 1999 inclusive. An analysis was carried out of clinical records and other records kept by clinicians and staff at the centre. Outcome measures were numbers of days of retention in treatment and reasons for departure, categorized as completed treatment, planned or unplanned departure and expulsion from the programme. For patients who underwent in-house detoxification, a further outcome measure was whether or not detoxification was complete at discharge. RESULTS: Heroin was the main drug of abuse in 85% of admissions. Mean length of time for which individuals had been drug dependent was 8 years (range 1.3-20.1 years). The mean length of stay was 80.2 days (range 1-394, 95% confidence interval 61.8-98.6). Thirty-four individuals (25%) completed 90 days or more. No association was found between length of stay and age, sex, route of administration, polydrug use, length of time addicted or age of first addiction. Sixty-five per cent of those who received in-house detoxification completed the detoxification period. When patients were classified as 'successes' or 'failures' by reason for departure from the programme, 94 (68.1%) were classified as failures and 18 (13.0%) as successes. Data were unavailable for 26 patients. Success was not associated with any characteristic at entry apart from being drug free as opposed to requiring detoxification (P = 0.048, chi-square = 6.06, df = 2). CONCLUSION: This study shows overall low levels of programme completion and high levels of unplanned departure and eviction from the programme amongst these long-term drug users. On the other hand, the importance of abstinence for those who achieve it in residential rehabilitation should not be underestimated, nor should the possibility that long-term outcomes are influenced by the learning process involved in the intervention. It may be possible to operate better selection procedures in order to optimize outcomes.

Adult↗
PubMed2001

High leptin levels acutely inhibit insulin-stimulated glucose uptake without affecting glucose transporter 4 translocation in l6 rat skeletal muscle cells.

Obesity is a major risk factor for the development of insulin resistance, characterized by impaired stimulation of glucose disposal into muscle. The mechanisms underlying insulin resistance are unknown. Here we examine the direct effect of leptin, the product of the obesity gene, on insulin-stimulated glucose uptake in cultured rat skeletal muscle cells. Preincubation of L6 myotubes with leptin (2 or 100 nM, 30 min) had no effect on basal glucose uptake but reduced insulin-stimulated glucose uptake. However, leptin had no effect on the insulin-induced gain in myc-tagged glucose transporter 4 (GLUT4) appearance at the cell surface of L6 myotubes. Preincubation of cells with leptin also had no effect on insulin-stimulated tyrosine phosphorylation of insulin receptor, IRS-1 and IRS-2, phosphatidylinositol 3-kinase activity, or Akt phosphorylation. We have previously shown that insulin regulates glucose uptake via a signaling pathway sensitive to inhibitors of p38 MAP kinase. Here, leptin pretreatment reduced the extent of insulin-stimulated p38 MAP kinase phosphorylation and phosphorylation of cAMP response element binder, a downstream effector of p38 MAP kinase. These results show that high leptin levels can directly reduce insulin-stimulated glucose uptake in L6 muscle cells despite normal GLUT4 translocation. The mechanism of this effect could involve inhibition of insulin-stimulated p38 MAP kinase and GLUT4 activation.

Animals↗
PubMed2001

Deaths from drugs of abuse in Sheffield, 1998: the role of prescribed medication.

Characteristics of recent drug abuse-related deaths in the city of Sheffield were examined from the coroner's records. Almost all of those who died of poisoning from a drug of abuse were known to be dependent on heroin yet less than half were receiving treatment. Benzodiazepines were frequently detected alongside opiates during toxicology, the source of which was likely to be the deceased's own prescription.

Adult↗
PubMed2000

Keeping families of heroin addicts together: results of 13 months' intake for community detoxification and rehabilitation at a family centre for drug users.

BACKGROUND: Heroin addiction is a major public health problem affecting both the addicted individuals and their children, who have been shown to have poor social, educational and health status and to be at higher risk of abuse than their peers. Whilst the antenatal effects of parental drug use and the overall poor outcomes for these children have been widely studied, there has been little emphasis on the effectiveness of treatment interventions and even less emphasis on evaluating the effect on children of the standard treatments aimed at their parents' drug use. OBJECTIVES: The aim of the present study was to evaluate the effect on heroin-addicted parents and their children of a family-based drug treatment intervention using a records-based methodology, and to identify any factors at admission which may influence outcome. This study is a pilot for a prospective Europe-wide study using a similar methodology prospectively in several treatment modalities. METHODS: A retrospective cohort study was carried out using existing clinical and residential record data. The setting was a residential family centre run by the charity Phoenix House in Sheffield, UK, offering a 6-month (180 days) family-based programme for heroin addicts including community detoxification overseen by primary care specialist doctors and residential rehabilitation. All adults and children who entered the centre between July 1997 and July 1998 were included in the study (26 adults and 33 children, in 23 family groups). An analysis was made of clinical records and records kept on the adults and children by the clinicians and staff at the centre. The main outcome measures for the adults were length of stay and reason for departure (treatment complete, early planned discharge, unplanned discharge, eviction); and for the children were reason for departure and discharge destination (with parent or taken into care). RESULTS: Mean length of stay was 110 days, and only 11 children (33%) and nine adults (35%) completed 150 days or more. Length of stay was found to be significantly correlated with parental age at admission (P < 0.01). Twelve children (37%) and nine adults (35%) were deemed to have completed treatment successfully. Of the remainder, 14 children (42%) and 11 adults (42%) left because of definite treatment failure. Successful treatment completion was found to be correlated with increased parental age (Pearson's r = 0.612, P = 0. 001). Poly-drug users were significantly less likely to complete treatment successfully (Fisher's exact test, P = 0.012). Twenty children were in the care of their parents on admission, and 24 were able to go home with their parents. There was no association between residence with parents pre- and post-admission (McNemar's chi-squared test = 1.6, P > or = 0.1). CONCLUSIONS: Whilst overall high rates of treatment success are not expected in abstinence-based programmes, the outcomes for the adults in this setting are comparable with published results in other residential settings, and there is some evidence that some families may have stayed together who might otherwise have been separated. Older adults who were not poly-drug users had significantly better outcomes. The records-based methodology proved successful, but centres need to keep detailed and preferably long-term records on children if their outcomes are to be evaluated more fully.

Adult↗
PubMed2000

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. Here, we explore whether such stimulation is observed in rat skeletal muscle and whether muscle contraction can also affect the enzyme. Insulin injection (2 U over 3.5 min) resulted in increases in p38 MAPK phosphorylation measured in soleus (3.2-fold) and quadriceps (2.2-fold) muscles. Increased phosphorylation (3.5-fold) of an endogenous substrate of p38 MAPK, cAMP response element binder (CREB), was also observed. After in vivo insulin treatment, p38 MAPKalpha and p38 MAPKbeta isoforms were found to be activated (2.1- and 2.4-fold, respectively), using an in vitro kinase assay, in immunoprecipitates from quadriceps muscle extracts. In vitro insulin treatment (1 nmol/l over 4 min) and electrically-induced contraction of isolated extensor digitorum longus (EDL) muscle also doubled the kinase activity of p38 MAPKalpha and p38 MAPKbeta. The activity of both isoforms was inhibited in vitro by 10 micromol/l SB203580 in all muscles. To explore the possible participation of p38 MAPK in the stimulation of glucose uptake, EDL and soleus muscles were exposed to increasing doses of SB203580 before and during stimulation by insulin or contraction. SB203580 caused a significant reduction in the insulin- or contraction-stimulated 2-deoxyglucose uptake. Maximal inhibition (50-60%) occurred with 10 micromol/l SB203580. These results show that p38 MAPKalpha and -beta isoforms are activated by insulin and contraction in skeletal muscle. The data further suggest that activation of p38 MAPK may participate in the stimulation of glucose uptake by both stimuli in rat skeletal muscle.

Animals↗
PubMed2000

Can methadone maintenance for heroin-dependent patients retained in general practice reduce criminal conviction rates and time spent in prison?

A retrospective analysis was made of the criminal records of 57 patients successfully retained in methadone maintenance at two general practices in Sheffield. Their criminal conviction rates and time spent in prison per year were compared for the periods before and after the start of their methadone programme. Overall, patients retained on methadone programmes in the general practices studied had significantly fewer convictions and cautions, and spent significantly less time in prison than they had before the start of treatment.

Adult↗
PubMed1999

Freedom of information. Quietly does it.

The forthcoming legislation on freedom of information is likely to be far less radical than originally envisaged. Decisions over what information to release will rest with civil servants. The legislation is likely to require primary care groups to respond to requests for information about allocation of resources between services. Access to the workings of government and the evidence underlying policy decisions would enable people to become active citizens. It would also stimulate sympathy for managers' and clinicians' rationing dilemmas. Current restrictions are at odds with government policy to modernize the NHS.

Consumer Advocacy↗
PubMed1999

Skeletal muscle and small-conductance calcium-activated potassium channels.

Skeletal muscle becomes hyperexcitable following denervation and when cultured in the absence of nerve cells. In these circumstances, the bee venom peptide toxin apamin, a blocker of small-conductance calcium-activated potassium (SK) channels, dramatically reduces the hyperexcitability. In this report, we show that SK3 channels are expressed in denervated skeletal muscle and in L6 cells. Action potentials evoked from normal innervated rat skeletal muscle did not exhibit an afterhyperpolarization, indicating a lack of SK channel activity; very low levels of apamin binding sites, SK3 protein, or SK3 mRNA were present. However, denervation resulted in apamin-sensitive afterhyperpolarizations and increased apamin binding sites, SK3 protein, and SK3 mRNA. Cultured rat L6 myoblasts and differentiated L6 myotubes contained similar levels of SK3 mRNA, although apamin-sensitive SK currents and apamin binding sites were detected only following myotube differentiation. Therefore, different molecular mechanisms govern SK3 expression levels in denervated muscle compared with muscle cells differentiated in culture.

Animals↗