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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 181 records · Page 10Linked to original sources
PubMed1996

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups (Br. J. Anaesth. 1996; 76: 606-610).

Adult↗
PubMed1996

Microangiopathic haemolytic anaemia and systemic vasculitis.

Two cases of systemic vasculitis complicated by microangiopathic haemolytic anaemia (MAHA) are described: this association has not previously been reported. Both patients had atypical presentations of their primary disease, one with parotitis and one with a Guillain-Barré syndrome. Other causes of MAHA were excluded and a possible link with macromolecular von Willebrands factor is speculated upon.

Aged↗
PubMed1996

An extracellular enzyme with hyaluronidase and chondroitinase activities from some oral anaerobic spirochaetes.

Treponema denticola, Treponema vincentii and Treponema socranskii produce an enzyme that hydrolyses hyaluronic acid (HA) and chondroitin sulphate (CS). The secreted enzyme is specifically inhibited by gold sodium thiomalate and anti-bee-venom antibodies. The use of saturated substrate (HA or CS) transblots allowed the visualization of active enzyme directly from culture supernatants and is a useful tool in clarification of complex polysaccharide-degrading enzyme specificities. The affinity-purified extracellular enzyme of T. denticola contains a single molecular species with a molecular mass of 59 kDa. Since it hydrolyses both HA and CS, it can more appropriately be termed a hyaluronoglucosaminidase (HGase). The HGase has been localized at the cell surface by electron microscopy and may play an active role in the degradation of connective tissue ground substance in the initiation and progression of periodontal disease.

Antibodies, Blocking↗
PubMed1996

Rothmund-Thomson syndrome: two case reports show heterogeneous cutaneous abnormalities, an association with genetically programmed ageing changes, and increased chromosomal radiosensitivity.

Rothmund-Thomson syndrome is a rare, autosomal recessive disorder associated with characteristic cutaneous changes, sparse hair, juvenile cataracts, short stature, skeletal defects, dystrophic teeth and nails, and hypogonadism. Mental retardation is unusual. An increased incidence of certain malignancies has been reported. Clonal or mosaic chromosome abnormalities and abnormalities in DNA repair mechanisms have been reported in some cases. We report two cases of Rothmund-Thomson syndrome, both with intellectual handicap, associated in one with a previously undescribed histological appearance of involved skin, suggesting that the spectrum of abnormalities is even more heterogeneous than previously presumed. Both cases exhibited chromosomal radiosensitivity of lymphocytes which may be an indication of a DNA repair defect. This is the first report of an association between Rothmund-Thomson syndrome and unique, intrinsic, age related skin changes.

Adolescent↗
PubMed1996

Iron acquisition by oral hemolytic spirochetes: isolation of a hemin-binding protein and identification of iron reductase activity.

Oral anaerobic spirochetes (OAS) have been implicated in the etiology of periodontal disease. To adapt to the environment of the subgingiva, OAS must be able to acquire iron from limited sources. OAS have previously been shown not to produce siderophores but are beta-hemolytic and can bind hemin via a proteinaceous 47-kDa outer membrane sheath (OMS) receptor. Present studies show that [3H]hemin is not transported into the cytoplasm, that hemin and ferric ammonium citrate, as the sole iron sources, can support the growth of OAS and that protoporphyrin IX and Congo red are inhibitory, thereby implying an important in vivo role for hemin as an iron source. Treponema denticola ATCC 35405 produces an iron reductase. The iron reductase can reduce the central ferric iron moiety of hemin. The 47-kDa OMS hemin-binding protein has been purified to apparent homogeneity by methanol-chloroform extraction of cellular lipoproteins and the use of a hemin-agarose bead affinity column. A model of iron acquisition by OAS is presented.

Bacterial Outer Membrane Proteins↗
PubMed1996

The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.

We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydro-epiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.

Adult↗
PubMed1996

A pilot study of nonverbal cues in videotelecommunication.

With the increasing popularity of low-cost videocommunications systems and their attendant low bandwidth-resolution problems, receivers are likely to experience difficulties in recognising the sender's intended expression and feeling. As an extension of previous work in the area, this pilot study investigated the effects of three forms of degraded imaging (and their combined effects) on the nonverbal aspects of communication for one person. Degraded video messages significantly impaired the meaning of the sender.

Adult↗
PubMed1996

The role of positive and negative affect in flashbulb memory.

All previous reports on the phenomenon of flashbulb memories relate to hearing of shocking (or "bad") news: in other words, that of negative affect. This study represents the first attempt to investigate whether those criteria used to define flashbulb memories would similarly apply to events of similar strength but of positive affect. 70 questionnaires were administered relating to 20 events over a 10-yr. period. No significant differences were found on the cardinal features of flasbhulb memories for events of negative versus positive affect. This suggests that an hitherto untapped research area may be explored to clarify controversial issues within this construct such as whether a special mechanism exists in the formation of flashbulb memories.

Adolescent↗
PubMed1996

Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition.

Sanford et al. (Int. J. Radiat. Biol. 55, 963-981, 1989) have reported that G2-phase cells from many heritable cancer-prone conditions exhibit higher yields of X-ray-induced chromosome damage than those found in the majority of healthy controls. We have applied their protocol to lymphocytes of a group of control and cancer-prone individuals to see if we could confirm these observations. For control donors we observed higher aberration yields, different kinetics and more interexperiment variability than found by Sanford et al. These differences could not be attributed to unavoidable minor variations in procedures (e.g. serum batches, glassware washing methods), but the difference in X-ray qualities used in the two laboratories may have made a small contribution to the discrepancies. We attribute some of our experimental variability to the fact that, to varying extents in different experiments, centrifugation of cells prior to irradiation can slow down the progression of cells into metaphase and that cells can continue to repair during the harvesting procedure (centrifugation and hypotonic treatment). We have applied the assay to cases of ataxia telangiectasia (AT, homozygotes and heterozygotes), xeroderma pigmentosum (homozygotes and heterozygotes), familial adenomatous polyposis and the syndromes Li-Fraumeni, basal cell nevus, Down's and Fanconi's but have been unable to discriminate between these groups and controls except for AT homozygotes. By including a control sample in parallel with samples from cancer-prone groups we found a significant difference in mean aberration yields between controls and AT homozygotes and heterozygotes, but not for the other groups. Since technical features could explain the discrepancies between our laboratories, we have devised our own G2-phase assay which appears to be giving promising results.

Adenomatous Polyposis Coli↗
PubMed1996

Gamma-ray-induced cell killing and chromosome abnormalities in the bone marrow of p53-deficient mice.

Resistance to the lethal effects of ionizing radiation has been demonstrated in a wide variety of cell types with defects in the p53 gene (thymocytes, splenic B and T cells, in vitro hemopoietic colony-forming cells and intestinal cells of the mouse, embryo cells of the rat, and human Burkitt's lymphoma cells). In contrast, Slichenmeyer et al. (Cancer Res. 53, 4164-4167, 1993) found no evidence of resistance in fibroblasts derived from p53 null mice. The aim of our study was to compare the radiation response of hemopoietic colony-forming cells (in vitro CFC) and of fibroblastoid colony-forming cells or units (CFU-F) within the same tissue (marrow) in p53 null mice (-/-), heterozygotes (+/-) and wild-type animals (+/+). We have also tested the hypothesis that, in proliferating cells, radiation-induced cell killing is mediated through chromosome damage by examining the relationship between these end points in hemopoietic cells of the three mouse types. Both in vitro CFC and CFU-F of -/- mice were resistant to cell killing compared with +/+ and +/- mice whose cellular sensitivities were indistinguishable. The resistance was characterized by a broader "shoulder" on the cell survival curve, i.e. a higher extrapolation number but similar D0 values using the multitarget model or a lower alpha coefficient using the linear-quadratic model. The frequency of chromosomally abnormal marrow cells after irradiation was similar for the three genotypes. However, marrow cells with aberrations carried more aberrations in -/- mice than in +/+ or +/- mice such that the total number of aberrations per 100 cells was higher in -/- mice. Since there were no differences in the yields of aberrations between genotypes in spleen lymphocytes or in CFU-F (both noncycling at the time of irradiation) and less mitotic inhibition in -/- marrow cells than in +/+ or +/- cells, the chromosomal radiosensitivity of -/- marrow hemopoietic cells might be related to reduced cell cycle delay allowing insufficient time for repair, but other explanations have been considered. We postulate that the radiation resistance of both hemopoietic CFC and CFU-F in -/- mice is a consequence of the failure of DNA/chromosome damage to trigger apoptosis or permanent cell cycle arrest to the same extent as in the +/+ or +/- mice: hence the lack of correlation between chromosome damage and cell death in the three mouse types.

Analysis of Variance↗
PubMed1996

Incidence of rheumatoid arthritis is not related to indicators of socioeconomic deprivation.

OBJECTIVE: To evaluate the role of socioeconomic factors in susceptibility to rheumatoid arthritis (RA). METHODS: A prospective population based register of inflammatory joint disease (NOAR) recruited 687 adults between 1990 and 1992, of whom 50% satisfied ARA criteria for RA at presentation. Using census data, social class specific incidence rates were calculated for both sexes. A correlation analysis was undertaken examining the association between incidence rates and 5 indicators of socioeconomic status. RESULTS: There was no trend of increasing incidence with declining social class. None of the 5 indicators examined showed any evidence of association with incidence (rs range 0.0-0.3). CONCLUSION: In contrast to the data on factors influencing outcome in established RA, the socioeconomic status variables examined did not explain susceptibility patterns in the population studied.

Adult↗
PubMed1995

Rational design and synthesis of small molecule, non-oligosaccharide selectin inhibitors: (alpha-D-mannopyranosyloxy)biphenyl-substituted carboxylic acids.

The calcium dependent E-selectin/sialyl Lewisx (sLex) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLex binding, along with previously reported structure-activity relationships of sLex-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLex expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLex tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

Animals↗
PubMed1995

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures.

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential-colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC-IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40-fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.

Animals↗
PubMed1995

A single amino acid residue can determine the ligand specificity of E-selectin.

E-selectin (ELAM-1) is a member of the selectin family of cellular adhesion molecules. This family of proteins possesses an amino-terminal Ca(2+)-dependent lectin or carbohydrate recognition domain that is essential for ligand binding. A known E-selectin ligand is the carbohydrate antigen, sialyl Lewis(x) (sLe(x) (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc). We have developed a model of E-selectin binding to the sLe(x) tetrasaccharide, (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc), using the NMR-determined, E-selectin-bound solution conformation of sLe(x) (Cooke, R.M., Hale, R.S., Lister, S. G., Shah, G., and Weir, M. P. (1994) Biochemistry 33, 10591-10596) together with the x-ray crystallographic structures of E-selectin (Graves, B. J., Crowther, R. L., Chandran, C., Rumberger, J. B., Li, s., Huang, K.-S., Presky, D. H., Familletti, P. C., Wolitzky, B. A., and Burns, D. K. (1994) Nature 367, 532-538) (ligand unbound) and a related C-type animal lectin, the mannose-binding protein (Weis, W. I., Drickamer, K., and Hendrickson, A. (1992) Nature 360, 127-134) (ligand bound). Analysis of this model indicated that the alteration of one E-selectin amino acid, alanine 77, to a lysine residue might shift binding specificity from sLe(x) to mannose. The results presented here show that an E-selectin mutant protein possessing this change displays preferential binding to mannose containing oligosaccharides and that further mutagenesis of this mannose-binding selectin confers galactose recognition in a predictable manner. These mutagenesis data support the presented model of the detailed interactions between E-selectin and the sLe(x) oligosaccharide.

Amino Acid Sequence↗
PubMed1995

Foot care among diabetic patients in south Auckland.

AIM: To describe footcare among diabetic patients in south Auckland. METHOD: Direct interview of 331 European, 86 Maori and 123 Pacific Islands patients attending local diabetes services and a stratified subsample of general practitioners. Interviews included closed and open questions of diabetes knowledge, demographic and medical history and were followed by a thorough inspection of the feet. RESULTS: Major lesions (amputation, foot ulcer) and predisposing lesions (callus or fungal infection/maceration) were present in 48.5% of patients. Major lesions were particularly common among Pacific Islands patients (9.4%) vs European (3.9%), Maori (5.5%), (p < 0.05). Fungal infection/maceration was less common among Pacific Islands patients (23.0%) vs 42.3%, 42.2% respectively, (p < 0.001). Fungal infection/maceration was more common and callus formation less common among men when compared with women. Forty percent (n = 214) of patients, including eight with either an ulcer or a blister, had not had their feet examined over the preceding 12 months. Good foot care was present in 52.7% Europeans, 31.0% Maori and 26.8% Pacific Islands patients (p < 0.001). Diabetes knowledge was poorest in those with poor foot care among Europeans and Maori. CONCLUSION: While the provision of footcare advice, adherence to such advice and monitoring of footcare remain uneven, the hospital and community costs of the diabetic foot will continue to be high.

Adolescent↗
PubMed1995

Role of B7:CD28/CTLA-4 in the induction of chronic relapsing experimental allergic encephalomyelitis.

T cell activation requires both Ag/MHC recognition and costimulatory signals. The present studies were designed to test whether the loss of tolerance to myelin basic protein (MBP) requires costimulation by members of the B7 receptor family. CTLA-4Ig, a fusion protein ligand for B7-1 and B7-2, was used to assess the role of B7-mediated costimulation in chronic relapsing experimental allergic encephalomyelitis (EAE) induced by the transfer of MBP specific T cell lines. In adoptively transferred EAE, administering CTLA-4Ig to donor mice or during in vitro activation of MBP specific-T cells resulted in diminution of clinical disease. The presence of CTLA-4Ig during both the immunization and in vitro activation stages was most effective in preventing clinical signs of disease. This diminution in clinical disease was paralleled by a decreased proliferative response and reduced production of IL-2 and IL-4, but not IFN-gamma, after antigenic stimulation of encephalitogenic T cells in vitro. In contrast, CTLA-4Ig treatment of recipient animals after the transfer of MBP-activated T cells affected neither disease course nor severity. These results indicate that additional costimulatory pathways may be involved in established EAE, or that some cells are independent of costimulation or, alternatively, that CTLA-4Ig does not enter brain parenchyma in therapeutic concentrations. Thus, we conclude that costimulation provided by B7 molecules plays a major role in the development of encephalitogenic T cells and in the establishment of chronic relapsing EAE, a prototypic CD4+ T cell-mediated autoimmune disease.

Abatacept↗