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Biomedical subjects

S Scott

Publications and source records attributed to S Scott.

At least 37 records · Page 2Linked to original sources

Hand exsanguination: prospective randomised blind study of an established versus a modified technique.

One hundred patients undergoing elective hand surgery were randomized to have their hands exsanguinated by either the Rhys-Davies exsanguinator alone or the Rhys-Davies exsanguinator supplemented by a 500 ml bag of intravenous fluid which was placed in the patient's palm as the exsanguinator was rolled up the limb. The quality of the exsanguination was assessed by the surgeon using a pre-defined subjective scoring system. There were no significant differences in the exsanguination scores of the two treatment groups.

Blood Loss, Surgical↗

Review of a pilot quality-assessment program for interpretative comments.

BACKGROUND: Interpretative commenting constitutes an important aspect of the post-analytical phase in chemical pathology, but has only recently been the subject of quality assessment. The Royal College of Pathologists of Australasia (RCPA)-Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program is currently in its third year, having started in 2000 as a pilot program. We present a review of the pilot program. METHODS: The program is aimed at individuals rather than laboratories. Two cases were circulated to participants of the Chemical Pathology Quality Assurance Program every month over a 6-month period. The case report contained the age and sex of the patient, together with brief clinical notes, the biochemistry results for commenting and other information of relevance. Three lines of space were given for the comment. The comments received from participants were broken down into their components and translated into common key phrases for the purpose of summarization and analysis. A histogram of the frequency of use of the common key phrases was generated. The comments or the key phrases were not given scores or marks, nor was any other indication given as to the appropriateness of their comments. RESULTS: This approach of simple peer-group comparison of comments without any assessment of the appropriateness of the comments was found to be inadequate; thus, when the program continues, key phrases will be classified according to degree of appropriateness and a suggested comment for each case will be proposed by an 'expert' panel. CONCLUSIONS: The program can serve a useful role in continuing education. Clinical biochemists and trainees who add interpretative comments to results produced by their laboratory, or give interpretative advice over the telephone, may potentially benefit from participating in this program.

Aged↗

Spinal anaesthesia: comparison of plain ropivacaine 5 mg ml(-1) with bupivacaine 5 mg ml(-1) for major orthopaedic surgery.

BACKGROUND: Ropivacaine provides effective spinal anaesthesia for total hip arthroplasty. This study was designed to compare the efficacy and safety of plain ropivacaine with plain bupivacaine for spinal anaesthesia in patients undergoing total hip arthroplasty. METHODS: Sixty-six patients, ASA I or II, were randomized to receive an intrathecal injection of one of two local anaesthetic solutions. Group R (n=32) received 3.5 ml of ropivacaine 5 mg ml(-1) (17.5 mg). Group B (n=34) received 3.5 ml of bupivacaine 5 mg ml(-1) (17.5 mg). The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. RESULTS: Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 2-5 min) in Group R and 2 min in Group B (range 2-9 min). The median duration of sensory block at the T10 dermatome was 3.0 h (range 1.5-4.6 h) in Group R and 3.5 h (2.7-5.2 h) in Group B (P<0.0001). The median duration of complete motor block (modified Bromage Scale 3) was significantly shorter in the ropivacaine group compared with the bupivacaine group (2.1 vs 3.9 h, P<0.001). CONCLUSIONS: Intrathecal administration of either 17.5 mg plain ropivacaine or 17.5 mg plain bupivacaine was well tolerated and an adequate block for total hip arthroplasty was achieved in all patients. A more rapid postoperative recovery of sensory and motor function was seen in Group R compared with Group B.

Adult↗

Delivering adjuvant chemotherapy to women with early-stage breast carcinoma: current patterns of care.

BACKGROUND: Variations in practice patterns are markers for the quality of patient care in general medicine, but little is known about variation in care delivered to cancer patients. This study's purpose was to describe chemotherapy use, variations in chemotherapy delivery, and the incidence of complications in community practice settings. METHODS: Data describing adjuvant chemotherapy for patients with early-stage breast carcinoma (ESBC) were collected from an ongoing Oncology Practice Pattern Study at 13 large managed care, academic, and community practices (1111 patients). Data collection included information about diagnoses and adjuvant chemotherapy treatments, laboratory results, supportive care, complications, and treatment modifications. RESULTS: The median patient age was 50 years, and most patients had zero to three positive lymph nodes. Chemotherapy regimens consisting of cyclophosphamide, methotrexate, and 5-fluororacil (CMF) and of doxorubicin and cyclophosphamide (AC) accounted for 76% of the adjuvant therapies used. Overall, 30% of patients had delivered average relative dose intensities </= 85% of the referenced targets. Delivered summation dose intensities (SDIs) frequently were well below targeted SDIs. Neutropenia-related dose modifications occurred for 27.6% of patients and recurred with a 60.7% rate. AC was the regimen delivered with a dose intensity closest to the referenced target. However, patients who were treated with AC regimens and with regimens consisting of cyclophosphamide, doxorubicin, and 5-fluorouracil had significantly higher rates of chemotherapy-related complications compared with patients who were treated with CMF regimens in the most recent treatment years. CONCLUSIONS: Adjuvant chemotherapy for patients with ESBC frequently is not administered as referenced in off-protocol community settings. Variation in the delivered SDI raises concerns about potential treatment outcomes and warrants strategies to identify patients who are at risk for complications early in therapy.

Adult↗

Financial cost of social exclusion: follow up study of antisocial children into adulthood.

OBJECTIVES: To compare the cumulative costs of public services used through to adulthood by individuals with three levels of antisocial behaviour in childhood. DESIGN: Costs applied to data of 10 year old children from the inner London longitudinal study selectively followed up to adulthood. SETTING: Inner London borough. PARTICIPANTS: 142 individuals divided into three groups in childhood: no problems, conduct problems, and conduct disorder. MAIN OUTCOME MEASURES: Costs in 1998 prices for public services (excluding private, voluntary agency, indirect, and personal costs) used over and above basic universal provision. RESULTS: By age 28, costs for individuals with conduct disorder were 10.0 times higher than for those with no problems (95% confidence interval of bootstrap ratio 3.6 to 20.9) and 3.5 times higher than for those with conduct problems (1.7 to 6.2). Mean individual total costs were 70 019 pounds sterling for the conduct disorder group (bootstrap mean difference from no problem group 62 pound sterling; 898 pound sterling 22 692 pound sterling to 117 pound sterling) and 24 324 pound sterling (16 707 pound sterling; 6594 pound sterling to 28 149 pound sterling) for the conduct problem group, compared with 7423 pound sterling for the no problem group. In all groups crime incurred the greatest cost, followed by extra educational provision, foster and residential care, and state benefits; health costs were smaller. Parental social class had a relatively small effect on antisocial behaviour, and although substantial independent contributions came from being male, having a low reading age, and attending more than two primary schools, conduct disorder still predicted the greatest cost. CONCLUSIONS: Antisocial behaviour in childhood is a major predictor of how much an individual will cost society. The cost is large and falls on many agencies, yet few agencies contribute to prevention, which could be cost effective.

Child↗

Multicentre controlled trial of parenting groups for childhood antisocial behaviour in clinical practice.

OBJECTIVE: To see whether a behaviourally based group parenting programme, delivered in regular clinical practice, is an effective treatment for antisocial behaviour in children. DESIGN: Controlled trial with permuted block design with allocation by date of referral. SETTING: Four local child and adolescent mental health services. PARTICIPANTS: 141 children aged 3-8 years referred with antisocial behaviour and allocated to parenting groups (90) or waiting list control (51). INTERVENTION: Webster-Stratton basic videotape programme administered to parents of six to eight children over 13-16 weeks. This programme emphasises engagement with parental emotions, rehearsal of behavioural strategies, and parental understanding of its scientific rationale. MAIN OUTCOME MEASURES: Semistructured parent interview and questionnaires about antisocial behaviour in children administered 5-7 months after entering trial; direct observation of parent-child interaction. RESULTS: Referred children were highly antisocial (above the 97th centile on interview measure). Children in the intervention group showed a large reduction in antisocial behaviour; those in the waiting list group did not change (effect size between groups 1.06 SD (95% confidence interval 0.71 to 1.41), P<0.001). Parents in the intervention group increased the proportion of praise to ineffective commands they gave their children threefold, while control parents reduced it by a third (effect size between groups 0.76 (0.16 to 1.36), P=0.018). If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16%. CONCLUSIONS: Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions. Follow up is needed to see if the children's poor prognosis is improved and criminality prevented.

Child↗

CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity.

Radiation is an effective means of treating localized prostate cancer. However, up to 40% of men with certain risk factors will develop biochemical failure 5 years after radiotherapy. CV706, a prostate cell-specific adenovirus variant, is currently in clinical trials for the treatment of recurrent organ-confined prostate cancer. We demonstrated previously that a single administration of CV706 at 5 x 10(8) particles/mm3 of tumor eliminated established tumors within 6 weeks in nude mouse xenografts (Rodriguez et al., Cancer Res. 57: 2559-2563, 1997). We now demonstrate that CV706-mediated cytotoxicity is synergistic with radiation. In vitro, addition of radiation to CV706 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP and a significant increase of virus burst size, with no reduction in specificity of CV706-based cytopathogenicity for prostate cancer cells. In vivo, prostate-specific antigen (+) LNCaP xenografts of human prostate cancer were treated with CV706 (1 x 10(7) particles/mm3 of tumor), 10 Gy of single fraction local tumor radiation, or both. Tumor volumes of the group treated with CV706 or radiation was 97% or 120% of baseline 6 weeks after treatment. However, when the same dose of CV706 was followed 24 h later with the same dose of radiation, the tumor volume dropped to 4% of baseline at this time point and produced antitumor activity that was 6.7-fold greater than a predicted additive effect of CV706 and radiation. Histological analyses of tumors revealed that, compared with CV706 or radiation alone, combination treatment with two agents increased necrosis by 180% and 690%, apoptosis by 330% and 880%, and decreased blood vessel number by 1290% and 600%, respectively. Importantly, no increase in toxicity was observed after combined treatment when compared with CV706 or radiation alone. These data demonstrate that CV706 enhances the in vivo radioresponse of prostate tumors and support the clinical development of CV706 as a neoadjuvant agent with radiation for localized prostate cancer.

Adenoviridae↗

Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies.

Recent studies have provided evidence that breast cancer susceptibility gene products (Brca1 and Brca2) suppress cancer, at least in part, by participating in DNA damage signaling and DNA repair. Brca1 is hyperphosphorylated in response to DNA damage and co-localizes with Rad51, a protein involved in homologous-recombination, and Nbs1.Mre11.Rad50, a complex required for both homologous-recombination and nonhomologous end joining repair of damaged DNA. Here, we report that there is a qualitative difference in the phosphorylation states of Brca1 between ionizing radiation (IR) and UV radiation. Brca1 is phosphorylated at Ser-1423 and Ser-1524 after IR and UV; however, Ser-1387 is specifically phosphorylated after IR, and Ser-1457 is predominantly phosphorylated after UV. These results suggest that different types of DNA-damaging agents might signal to Brca1 in different ways. We also provide evidence that the rapid phosphorylation of Brca1 at Ser-1423 and Ser-1524 after IR (but not after UV) is largely ataxia telangiectasia mutated (ATM) kinase-dependent. The overexpression of catalytically inactive ATM and Rad3 related (ATR) kinase inhibited the UV-induced phosphorylation of Brca1 at these sites, indicating that ATR controls Brca1 phosphorylation in vivo after the exposure of cells to UV light. Moreover, ATR associates with Brca1; ATR and Brca1 foci co-localize both in cells synchronized in S phase and after exposure of cells to DNA-damaging agents. ATR can itself phosphorylate the region of Brca1 phosphorylated by ATM (Ser-Gln cluster in the C terminus of Brca1, amino acids 1241-1530). However, there are additional uncharacterized ATR phosphorylation site(s) between residues 521 and 757 of Brca1. Taken together, our results support a model in which ATM and ATR act in parallel but somewhat overlapping pathways of DNA damage signaling but respond primarily to different types of DNA lesion.

Ataxia Telangiectasia↗

Deciding whether interventions for antisocial behaviour work: principles of outcome assessment, and practice in a multicentre trial.

Factors influencing the reported effectiveness of interventions for antisocial behaviour are reviewed, with illustrative findings from a multicentre controlled trial of parenting groups. The merits and validity of different types of measuring instrument are discussed and it is concluded that it is desirable to have more than one informant (parent, teacher, observer) and at least one instrument with objective criteria, for example a semi-structured interview or direct observation. In the illustrative trial, the effect size was larger with semi-structured interviews than questionnaires, for conduct problems compared to hyperactivity symptoms, and for trial completers compared to the total sample it was intended to treat. The discrepancy between the encouraging results of trials conducted in university centres and the disappointing findings of those carried out in 'real life' clinics is discussed. The trial discussed here was conducted in health service clinics by regular staff but still reported good effect sizes. Measuring likely mediators and moderators so mechanisms of change can be investigated is discussed. In the trial, change was mediated through acquisition of parenting skills but not through maternal depression or criticism directed at the child, even though these were reduced by the intervention. This suggests that programmes that impart skills are more likely to be effective than those that offer counselling only.

Attention Deficit and Disruptive Behavior Disorder↗

Current cementing techniques in hip hemi-arthroplasty.

To assess the use of modern cementing techniques in hip hemi-arthroplasty a postal questionnaire was sent during 1998 to all British Orthopaedic Training Association (B.O.T.A.) members regarding use of cement, type of cement, bone preparation and cementing technique. The results of this survey were compared to a similar survey in 1994 to assess any change in practice. Two hundred and eighty-six trainees responded to the 1998 survey, 352 to the 1994 survey. The use of uncemented prostheses had decreased from 31.3 in 1994 to 21.7% in 1998. Normal viscosity Palacos cement remains the most common cement in use, 64.3% in 1998. The use of antibiotic loaded cement has increased from 53.7 in 1994 to 67.9% in 1998. For bone preparation 47.3% of trainees in 1998 used a modern technique (syringe irrigation/pulsed lavage, brushing, gauze packing) compared to 35.1% in 1994. Modern cement insertion (retrograde gun, cement restriction and sustained pressure) was carried out by 39.3% in 1998 compared to 28.5% in 1994. Overall 27.2% of trainees used modern cementing techniques in hip hemi-arthroplasty, compared to 19.4% in 1994. Modern cementing techniques are used by a minority of British orthopaedic trainees, but in comparison to 1994 their use has increased.

Arthroplasty, Replacement, Hip↗

Oestrogens and oestrogenic activity in raw and treated water in Severn Trent Water.

Sewage effluent discharged to surface water has been shown to contain human hormones, particularly oestrogens, and synthetic chemicals which may be able to disrupt the endocrine system. Since many surface waters which receive sewage effluent are subsequently used as drinking water sources, it is important to demonstrate that treated drinking water is not contaminated. Oestrogenic activity in rivers and drinking water in the region of Severn Trent Water was studied using a combination of bioassay, to integrate exposure over time, and advanced chemical analysis. There was little or no evidence of substances that were oestrogenic, even in waters receiving significant amounts of sewage effluent. Oestrogenic activity, as measured in the rainbow trout vitellogenin assay, was seen at the Tame/Trent confluence but this activity was relatively weak. There was no activity detected at raw water intakes and no hormones or substances that are oestrogenic were detected in the final drinking water.

Animals↗

A survey of patient dose and image quality for computed tomography scanners in Wales.

The main aim of the study was to assess the current level of radiation dose from computed tomography scanning in the NHS in Wales and to compare these results with previous studies in Wales and the UK. In addition, the relationship between patient dose and image quality was investigated by comparing mean patient dose calculations with image noise using two quality assurance (QA) phantoms. The results show that although the introduction of spiral scanners has reduced the dose per examination, the collective dose per scanner has actually increased. The results also highlight the potential for relating dose and objective measures of image quality to assist in the selection of scanning parameters to optimise dose without compromising image quality.

Adult↗

Intrathecal ropivacaine for total hip arthroplasty: double-blind comparative study with isobaric 7.5 mg ml(-1) and 10 mg ml(-1) solutions.

This study was designed to evaluate the efficacy and safety of two concentrations of intrathecal ropivacaine, 7.5 and 10 mg ml(-1), in patients undergoing total hip arthroplasty. One hundred and four patients, ASA I-III, were randomized to receive an intrathecal injection of one of two concentrations of isobaric ropivacaine. Group 1 (n=51) received 2.5 ml of 7.5 mg ml(-1) ropivacaine (18.75 mg). Group 2 (n=53) received 2.5 ml of 10 mg ml(-1) ropivacaine (25 mg). The onset and offset of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 1-25 min) in Group 1 and 2 min (range 1-21 min) in Group 2. The median duration of sensory block at the T10 dermatome was 3.0 h (range 0.5-4.2 h) in Group 1 and 3.4 h (1.1-5.9 h) in Group 2 (P=0.002). The median duration of complete motor block was significantly prolonged (P<0.05) in Group 2 compared with Group 1 (1.9 vs 1.2 h, respectively). Anaesthetic conditions were excellent in all but one patient. Intrathecal ropivacaine, in doses of 18.75 and 25 mg, was well tolerated and provided effective anaesthesia for total hip arthroplasty.

Adult↗

CCR5, CXCR4, and CD4 are clustered and closely apposed on microvilli of human macrophages and T cells.

The chemokine receptors CCR5 and CXCR4 act synergistically with CD4 in an ordered multistep mechanism to allow the binding and entry of human immunodeficiency virus type 1 (HIV-1). The efficiency of such a coordinated mechanism depends on the spatial distribution of the participating molecules on the cell surface. Immunoelectron microscopy was performed to address the subcellular localization of the chemokine receptors and CD4 at high resolution. Cells were fixed, cryoprocessed, and frozen; 80-nm cryosections were double labeled with combinations of CCR5, CXCR4, and CD4 antibodies and then stained with immunogold. Surprisingly, CCR5, CXCR4, and CD4 were found predominantly on microvilli and appeared to form homogeneous microclusters in all cell types examined, including macrophages and T cells. Further, while mixed microclusters were not observed, homogeneous microclusters of CD4 and the chemokine receptors were frequently separated by distances less than the diameter of an HIV-1 virion. Such distributions are likely to facilitate cooperative interactions with HIV-1 during virus adsorption to and penetration of human leukocytes and have significant implications for development of therapeutically useful inhibitors of the entry process. Although the mechanism underlying clustering is not understood, clusters were observed in small trans-Golgi vesicles, implying that they were organized shortly after synthesis and well before insertion into the cellular membrane. Chemokine receptors normally act as sensors, detecting concentration gradients of their ligands and thus providing directional information for cellular migration during both normal homeostasis and inflammatory responses. Localization of these sensors on the microvilli should enable more precise monitoring of their environment, improving efficiency of the chemotactic process. Moreover, since selectins, some integrins, and actin are also located on or in the microvillus, this organelle has many of the major elements required for chemotaxis.

Animals↗

Developments in veterinary acupuncture.

Veterinary acupuncture has been developing rapidly in recent years. Public attention has been focused on acupuncture as a possible therapeutic intervention for their pets by the media. Interest in acupuncture from the veterinary profession has therefore been primarily driven by owner demand. Veterinarians are now seeking courses in acupuncture that are relevant to themselves as general practitioners rather than as specialists in complementary medicine. Evidence of the efficacy of acupuncture in treating any of the veterinary species is limited, so it is significant that two acupuncture-related trials at Glasgow University Veterinary School are currently receiving funding.

Acupuncture Therapy↗

Tissue inhibitor of metalloproteinase-1 prevents cytokine-mediated dysfunction and cytotoxicity in pancreatic islets and beta-cells.

In addition to inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, recent studies suggest that tissue inhibitor of metalloproteinase (TIMP)-1 may inhibit apoptosis in various cell lines. To address this question in pancreatic islets and beta-cells, we treated rat pancreatic islets and INS-1 cells with a high-dose combination of the cytokines interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma with or without the addition of TIMP-1 and TIMP-2 protein. Using flow cytometry, we quantitated DNA fragmentation to assess cellular apoptosis and confirmed these observations with DNA laddering experiments. Next, we transfected the mouse TIMP-1 gene into INS-1 cells and performed Western immunoblotting to demonstrate expression of TIMP-1 protein. We treated TIMP-1-expressing INS-1 cells with high-dose cytokines and again used flow cytometry to assess DNA fragmentation. We also evaluated the effect of TIMP-1 on IL-1beta-induced inhibition of glucose-stimulated insulin secretion (GSIS) in freshly isolated rat pancreatic islets. Finally, we evaluated the effect of TIMP-1 on inducible nitric oxide synthase (iNOS) gene expression and nuclear factor (NF)-kappaB activity in INS-1 cells stimulated with high-dose cytokines. TIMP-1 but not TIMP-2 prevented cytokine-induced apoptosis and cytokine-mediated inhibition of GSIS in rat islets and beta-cells. TIMP-1 mediated these effects by inhibiting cytokine activation of NF-kappaB, but it did not affect nitric oxide production or iNOS gene expression. Therefore, TIMP-1 may be an ideal gene to prevent cytokine-mediated beta-cell destruction and dysfunction in models of type 1 diabetes and islet transplantation rejection.

Animals↗