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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 433 records · Page 24Linked to original sources
PubMed1997

Evaluating large scale health information systems: from practice towards theory.

With the introduction of large scale health information systems which are incrementally developed from legacy systems, evaluators are faced with difficult methodological and practical problems. Some of the problems involved in multidisciplinary multi-method evaluations care discussed. It is argued that the development of a framework for evaluation is necessary in order to successfully plan an evaluation, understand the implications of the results and make future predictions based upon them. Some suggestions for arriving at such a framework are put forward.

Evaluation Studies as Topic↗
PubMed1997

Using clinical indicators to change clinical practice.

A study of the qualitative information received by the Australian Council on Healthcare Standards (ACHS) Care Evaluation Program (CEP) in 1993 showed that the monitoring of clinical indicators had the potential to stimulate a variety of quality activities within health-care organizations. To determine whether the potential for improved patient outcomes has continued, the ACHS CEP conducted a survey of those organizations which submitted clinical indicator data as part of their accreditation survey in 1995. Analysis of the qualitative data received showed that change was reported on 505 occasions by organizations monitoring the hospital-wide medical and obstetrics and gynaecology clinical indicator sets. Details of 251 reported changes were received through a follow-up survey. These details provide evidence that clinical indicators are being used to implement changes in clinical practice to improve the quality of patient care.

Australia↗
PubMed1997

Putting principals back into practice: an evaluation of a re-entry course for vocationally trained doctors.

BACKGROUND: Current recruitment difficulties in general practice have sharpened the interest of the profession in non-principals. No re-entry course for general practice has previously been run in the UK. AIM: To design and evaluate a re-entry course for general practice. METHOD: A re-entry course was developed to help doctors return to general practice as principals. A telephone interview was carried out with each delegate prior to their attendance on the course and was repeated one month and six months after the course to measure any change in career intentions and the perceived benefit of attending the course. RESULTS: Six months after the course, 11 out of 14 delegates had taken positive steps to return to general practice or had increased their time commitment to medicine. This contrasts with only one of the control group having made any steps to change career. CONCLUSION: The course was evaluated and found to be beneficial, particularly in terms of increasing the confidence of the delegates.

Curriculum↗
PubMed1997

Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing.

Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival. Fifty-four previously untreated patients with limited-stage small cell cancer were studied. Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment. The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs. From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected. Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy. This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide. Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST. The biopsy specimens contained tumor cells in 16 of 18 patients. The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P2 = 0.58). Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days). DST was done in 10 patients, and IVBR was administered to 8 patients. The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy. Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC. Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because of the nature of our study design, other factors could have affected the results.

Antineoplastic Agents↗
PubMed1996

Factor analysis of schizophrenic symptoms using the OPCRIT checklist.

Factor analysis was performed on OPCRIT checklist psychotic symptoms rated on 102 patients with DSM-III-R schizophrenia. An initial three-factor solution produced positive, negative, and disorganisation factors. However, application of the scree test suggested five substantive factors, with the positive factor dividing into three factors characterised, respectively, by paranoid symptoms, first rank delusions and first rank hallucinations.

Adult↗
PubMed1996

Induction of tolerance to small bowel allografts in high-responder rats by combining anti-CD4 with CTLA4Ig.

This study was designed to investigate the effectiveness of combined perioperative anti-CD4 and human (h)CTLA4Ig therapy in preventing allorejection of small bowel transplantation in high-responder Lewis rat recipients of ACI grafts. Anti-CD4 (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat x 2 days) therapy alone delayed, but did not prevent, allograft rejection after small bowel transplantation of ACI into Lewis rats. All grafts were rejected in 18 and 10 days, respectively. However, a regimen of anti-CD4 (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 2 days) allowed indefinite survival of ACI small bowel allografts. Second donor-matched heart grafts were permanently accepted, whereas third-party (Sprague-Dawley) heart allografts were rejected by the tolerant recipients. These data suggest that these two reagents produced a synergistic effect in preventing allorejection of small bowel transplantation.

Abatacept↗
PubMed1996

Lipopolysaccharide and interleukin 1 augment the effects of hypoxia and inflammation in human pulmonary arterial tissue.

The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor alpha on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1 beta, or tumor necrosis factor alpha augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.

Blotting, Northern↗
PubMed1996

cAMP-dependent protein kinase is required for the expression of a gene specifically expressed in Dictyostelium prestalk cells.

In the Dictyostelium slug there are two types of prestalk cells, pstA cells and pstO cells, that differ in their ability to utilize the distal and proximal parts of the promoter of ecmA, a gene that is specifically expressed in prestalk cells. When Rm, a dominant inhibitory form of the regulatory subunit of cAMP-dependent protein kinase (PKA), is expressed under the control of the complete promoter of the ecmA gene (in a construct termed ecmAO:Rm) development proceeds to the slug stage. Although able to form small but outwardly normal slugs, ecmAO:Rm cells are defective in prestalk cell differentiation. In ecmAO:Rm cells, the induction of pstA- and pstO-specific gene expression by the stalk cell inducer DIF is greatly inhibited. Paradoxically, a very large fraction of the cells in an ecmAO:Rm slug show evidence of once having expressed the ecmA and ecmO prestalk markers. However, we present evidence that this is due to abortive prestalk cell differentiation that terminates when sufficient Rm protein has accumulated to block PKA activity. This results in regulative transdifferentiation of prespore cells to form prestalk cells. During their transitory period as prestalk cells the ecmAO:Rm cells coexpress both the ecmA and ecmO markers, indicating a possible link between PKA activity and divergence of the two prestalk cell subtypes. Finally, we show that the level of the DNA binding activity believed to lie at the end of the DIF signal transduction pathway is reduced in ecmAO:Rm slugs.

Animals↗
PubMed1996

Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002.

The immunosuppressant, rapamycin, inhibits cell growth by interfering with the function of a novel kinase, termed mammalian target of rapamycin (mTOR). The putative catalytic domain of mTOR is similar to those of mammalian and yeast phosphatidylinositol (PI) 3-kinases. This study demonstrates that mTOR is a component of a cytokine-triggered protein kinase cascade leading to the phosphorylation of the eukaryotic initiation factor-4E (eIF-4E) binding protein, PHAS-1, in activated T lymphocytes. This event promotes G1 phase progression by stimulating eIF-4E-dependent translation initiation. A mutant YAC-1 T lymphoma cell line, which was selected for resistance to the growth-inhibitory action of rapamycin, was correspondingly resistant to the suppressive effect of this drug on PHAS-1 phosphorylation. In contrast, the PI 3-kinase inhibitor, wortmannin, reduced the phosphorylation of PHAS-1 in both rapamycin-sensitive and -resistant T cells. At similar drug concentrations (0.1-1 microM), wortmannin irreversibly inhibited the serine-specific autokinase activity of mTOR. The autokinase activity of mTOR was also sensitive to the structurally distinct PI 3-kinase inhibitor, LY294002, at concentrations (1-30 microM) nearly identical to those required for inhibition of the lipid kinase activity of the mammalian p85-p110 heterodimer. These studies indicate that the signaling functions of mTOR, and potentially those of other high molecular weight PI 3-kinase homologs, are directly affected by cellular treatment with wortmannin or LY294002.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Computer assisted learning (CAL) of oral manifestations of HIV disease.

General dental practitioners (GDPs) in the UK may wish additional education on relevant aspects of human immunodeficiency virus (HIV) disease. The aim of the present study was to develop and assess a computer assisted learning package on the oral manifestations of HIV disease of relevance to GDPs. A package was developed using a commercially-available software development tool and assessed by a group of 75 GDPs interested in education and computers. Fifty-four (72%) of the GDPs completed a self-administered questionnaire of their opinions of the package. The majority reported the package to be easy to load and run, that it provided clear instructions and displays, and that it was a more effective educational tool than videotapes, audiotapes, professional journals and textbooks, and of similar benefit as post-graduate courses. The GDPs often commented favourably on the effectiveness of the clinical images and use of questions and answers, although some had criticisms of these and other aspects of the package. As a consequence of this investigation the package has been modified and distributed to GDPs in England and Wales.

Adult↗
PubMed1996

Association between a PS-1 intronic polymorphism and late onset Alzheimer's disease.

Previous work suggests an association between allele 1 and the 1-1 genotype of an intronic polymorphism in the presenilin-1 (PS-1) gene and late onset Alzheimer's disease. We found an excess of the 1-1 genotype in our late onset clinical sample (p = 0.006, one-tailed) but not in our postmortem confirmed sample, which instead exhibited an excess of allele 1 (p = 0.02, one-tailed). No interaction between PS-1 and ApoE genotype was detected and the findings remained significant when the effects of ApoE were taken into account (p = 0.03, one-tailed). These results suggest that the PS-1 polymorphism, or a locus in linkage disequilibrium with it, acts as a risk factor for late onset AD.

Age of Onset↗
PubMed1996

Location of essential sequence elements at the Escherichia coli melAB promoter.

The Escherichia coli melAB promoter has been cloned on a short DNA fragment and subjected to deletion mutagenesis, random mutagenesis and site-directed mutagenesis. In previous work we had shown that expression from the melAB promoter is triggered by melibiose and that this requires the MelR transcription activator. Melibiose-dependent expression is suppressed by deletions that remove both DNA-binding sites for MelR and by point mutations in the -10 hexamer, the -35 hexamer and the region just upstream of the -35 hexamer. The point mutations identify promoter elements that are essential for triggering the melAB promoter. The importance of these elements was confirmed by site-directed mutagenesis. The results show that the organization of the melAB promoter is fundamentally different from the organization of other bacterial promoters controlled by homologues of MelR.

Base Sequence↗
PubMed1996

Platelet endothelial cell adhesion molecule-1 (PECAM-1) homophilic adhesion is mediated by immunoglobulin-like domains 1 and 2 and depends on the cytoplasmic domain and the level of surface expression.

PECAM-1/CD31 is vascular cell adhesion and signaling molecule of the Ig superfamily that plays a role in neutrophil recruitment at inflammatory sites and may be involved the release of leukocytes from the bone marrow and in cardiovascular development. The interactions of PECAM-1 with its ligands are complex in that it is able to bind both with itself (homophilic adhesion) or with non-PECAM-1 ligands (heterophilic adhesion). Although the factors that regulate ligand binding are not fully understood, these interactions are regulated in part by its large cytoplasmic domain, a region of 118 amino acids encoded by 8 exons of its gene (exons 9-16). The purpose of this work was to better define the mechanisms of PECAM-1-dependent homophilic adhesion by analyzing the binding interactions of L-cells expressing full-length and selectively mutated forms of human, murine, and human/murine chimeric PECAM-1 molecules in an established aggregation assay. These studies demonstrate that 1) the minimal length of the cytoplasmic domain required for cellular aggregation is represented within the sequences encoded by exons 9 and 10, 2) removal or addition of the sequences encoded by exon 14 from the cytoplasmic domain can determine whether the mechanism of aggregation is a heterophilic calcium-dependent process or a homophilic calcium-independent process, 3) high levels of surface expression of PECAM-1 on the cell surface change the mechanism of aggregation from heterophilic to homophilic, and 4) PECAM-1-dependent homophilic binding appears to involve the direct interaction of only the first two extracellular Ig-like domains. These data suggest that PECAM-1-ligand interactions can be regulated through multiple pathways including alterations of the cytoplasmic domain and the level of surface expression.

Animals↗