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Biomedical subjects

J Robertson

Publications and source records attributed to J Robertson.

At least 55 records · Page 3Linked to original sources

Estrogen replacement and brachial artery flow-mediated vasodilation in older women.

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

Aged↗

Social networks of people with mental retardation in residential settings.

Information was collected on the social networks of 500 adults with mental retardation receiving different types of residential supports. Results indicated that (a) the reported median size of participants' social networks (excluding staff) was 2 people; (b) 83% of participants were reported to have a staff member; 72%, a member of their family; 54%, another person with mental retardation; and 30%, a person who did not fit into any of these categories in their social network; (c) variation in the size and composition of participants' social networks was associated with a range of variables, including the personal characteristics of residents (age, autism, ability, and challenging behavior), the type of previous and current accommodation, staffing ratios, institutional climate, and the implementation of "active support."

Cross-Sectional Studies↗

Quality and costs of supported living residences and group homes in the United Kingdom.

Information was collected on 63 adults in supported living residences, 55 adults in small group homes, and 152 adults in large group homes. Results indicated that (a) there were no statistically significant differences in service costs once these had been adjusted to take account of participant characteristics; (b) compared with participants living in small group homes, those in supported living residences had greater choice, participated in more community-based activities, experienced fewer scheduled activities, were more likely to have had their home vandalized, and were considered at greater risk of exploitation; (c) compared with participants living in large group homes, those in small group homes had larger social networks, more people in their social networks who were not staff, not family, and did not have mental retardation. These residents were considered at less risk of abuse.

Adult↗

Recombinant bovine adenovirus type 3 expressing bovine viral diarrhea virus glycoprotein E2 induces an immune response in cotton rats.

Recombinant bovine adenovirus is being developed as a live vector for animal vaccination and for human gene therapy. In this study, two replication-competent bovine adenovirus 3 (BAV-3) recombinants (BAV331 and BAV338) expressing bovine viral diarrhea virus (BVDV) glycoprotein E2 in the early region 3 (E3) of BAV-3 were constructed. Recombinant BAV331 contains chemically synthesized E2 gene (nucleotides modified to remove internal cryptic splice sites) under the control of BAV-3 E3/major late promoter (MLP), while recombinant BAV338 contains original E2 gene under the control of human cytomegalovirus immediate early promoter. Since E2, a class I membrane glycoprotein, does not contain its own signal peptide sequence at the 5' end, the bovine herpesvirus 1 (BHV-1) glycoprotein D signal sequence was fused in frame to the E2 open reading frame (ORF) for proper processing of the E2 glycoprotein in both the recombinant viruses. Recombinant E2 protein expressed by BAV331 and BAV338 recombinant viruses was recognized by E2-specific monoclonal antibodies as a 53-kDa protein, which also formed dimer with an apparent molecular weight of 94 kDa. Insertion of an E2-expression cassette in the E3 region did not effect the replication of recombinant BAV-3s. Intranasal immunization of cotton rats with these recombinant viruses generated E2-specific IgA and IgG responses at the mucosal surfaces and in the serum. In summary, these results show that the pestivirus glycoprotein can be expressed efficiently by BAV-3. In addition, mucosal immunization with replication-competent recombinant bovine adenovirus 3 can induce a specific immune response against the expressed antigen.

Adenoviridae↗

Tumor necrosis factor receptor-associated factor 6 (TRAF6) deficiency results in exencephaly and is required for apoptosis within the developing CNS.

Tumor necrosis factor receptor-associated factors (TRAFs) are adaptor proteins important in mediating intracellular signaling. We report here that targeted deletion of traf6 greatly increases the frequency of failure of neural tube closure and exencephaly in traf6 (-/-) mice. The penetrance of this defect is influenced by genetic background. Neural tube fusion requires the coordination of several biological processes, including cell migration invoked by contact-dependent signaling, cell proliferation, and programmed cell death (PCD). To gain greater insight into the role of TRAF6 in these processes, neural development and migration within the CNS of traf6 (-/-) mice and controls were assessed through temporal examination of a number of immunohistochemical markers. In addition, relative levels of cellular proliferation and PCD were examined throughout embryonic development using bromodeoxyuridine (BrdU) and in situ terminal deoxynucleotidyl transferase-mediated dUTP biotinylated nick end labeling (TUNEL), respectively. The data suggest that loss of TRAF6 does not significantly alter the level of cellular proliferation or the pattern of neural differentiation per se, but rather regulates the level of PCD within specific regions of the developing CNS. Substantial reductions in TUNEL were observed within the ventral diencephalon and mesencephalon in exencephalic traf6 (-/-) embryos. Our results demonstrate a novel and prominent role for TRAF6 in the regional control of PCD within the developing CNS.

Animals↗

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus.

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.

Acarbose↗

Mutually exclusive expression of beta(III)-tubulin and vimentin in adrenal cortex carcinoma SW13 cells.

During embryogenesis, the maturation of neuroblasts into neurones is accompanied by the down-regulation of vimentin and by the expression of neuronal microtubular proteins. Here, we show that human adrenal cortex SW13 cells express beta(III)-tubulin, MAP2b and tau. Analysis of vimentin-positive and -negative subclones of SW13 cells revealed that, under defined cultured conditions, beta(III)-tubulin and MAP2b were present only in vimentin-deficient cells and that beta(III)-tubulin repression occurred at the transcriptional level in vimentin-positive cells. These results suggest that vimentin repression and beta(III)-tubulin expression are co-ordinated by an upstream mechanism relevant to the control of cytoskeletal protein expression during neuronal development.

Adenocarcinoma↗

Mini-review: history of organized teratology information services in North America.

A history of the Organization of Teratology Information Services (OTIS) is presented in context of the history of teratology information services. During the late 1970s, teratology information services grew out of the need for current and accurate information about fetal effects of environmental exposures in pregnancy. Over the next decade, teratology information services networked and collaborated, developing their own professional organization. A description of the activities of OTIS is described.

Female↗

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, BIOSIS, CINAHL, HealthPLAN, Dissertation Abstracts, Index to UK Theses, Current Contents, and bibliographies of identified trials and reviews. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: December 1995. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared Vitamin D or a Vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with fracture as an outcome, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a seven item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. MAIN RESULTS: Fourteen trials recording 13 different comparisons were included. In the only trial of Vitamin D alone, protection against hip fracture was not confirmed. Two regimens, each represented by one large trial, which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were: 1) Oral Vitamin D when accompanied by calcium supplementation. 2) 1,25 dihydroxy Vitamin D (calcitriol). This appeared more effective than calcium in a direct comparison. Regimens showing limited evidence of efficacy in reducing the incidence of vertebral deformity were: 1) 1,25 dihydroxy Vitamin D (calcitriol), which appeared more effective than calcium in one large trial, and more effective than placebo from pooled results of two small trials. 2) Oral 1-alpha hydroxy Vitamin D (alfacalcidol), when administered with calcium supplements (two small trials, which lacked power to confirm a possible effect). Hypercalcaemia and gastro-intestinal symptoms, reported in less than 5% of participants, were slightly more common when Vitamin D analogues were taken. However, the risk of death was marginally less. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further randomised trials with economic evaluation are desirable before community fracture prevention programmes employing Vitamin D supplementation can be confidently introduced.

Aged↗

Comparison of the Objective Structured Clinical Examination with the performance of third-year medical students in surgery.

BACKGROUND: The purpose of this study was to investigate the validity of the Objective Structured Clinical Examination (OSCE) as an evaluation technique by comparing medical student performance on the OSCE with traditional forms of evaluation. SUBJECTS AND METHODS: We analyzed the performance of 129 third-year medical students in the 1997-1998 academic year on clinical evaluations, oral examinations, and NBME subject examinations, and on OSCE, which was not included in the final grade. RESULTS: The OSCE showed high correlation with the final grades received for the clerkship. Seventy-one percent of students receiving High Pass or Honors had high OSCE scores whereas 67% of students with low OSCE scores received poor or Defer grades. Pearson product-moment correlations demonstrated significant bivariate correlations with the other test parameters. CONCLUSIONS: This study demonstrates that the OSCE is similar to the traditional methods in evaluating general ability and is also able to evaluate clinical ability in a standardized manner.

Analysis of Variance↗

Randomised study of anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women.

A total of 668 patients (340 anastrozole and 328 tamoxifen) were randomised in a double-blind, double-dummy multicentre study. Anastrozole was given in a dose of 1 mg once daily and compared with tamoxifen 20 mg daily in postmenopausal patients with tumours that were hormone-receptor positive or of unknown receptor status. The efficacy and tolerability of anastrozole was compared with that of tamoxifen as first-line therapy for advanced breast cancer. The median time to progression was similar for both treatments (8.2 months in anastrozole patients and 8.3 months in tamoxifen patients). Anastrozole was also as effective as tamoxifen in terms of objective response-rate with 33% in the anastrozole group and 32.6% in the tamoxifen group achieving a complete or partial response. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen. In conclusion, these findings indicate that anastrozole can be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Anastrozole↗

Detection of hTERT protein by flow cytometry.

Telomerase is a telomere-specific DNA polymerase consisting of protein and RNA components, which is activated in germline cells and the majority of cancers and serves to counter the consequences of telomere shortening. The protein component, hTERT, is believed to be the catalytic subunit of human telomerase and its expression at the mRNA level correlates well with telomerase activity in vitro. Current techniques for assaying telomerase activity detect only the mean activity in a sample and are unable to isolate specific cell sub-populations. This report describes the development and validation of a cellular, immunofluorescence-based flow cytometry assay that allows detection of intranuclear hTERT while maintaining identifiable cell population characteristics. The assay was shown to be both sensitive to changes in telomerase expression and was semi-quantitative. In both cell line differentiation experiments and in primary cells, a good correlation existed between hTERT expression measured by flow cytometry and telomerase activity detected by the telomeric repeat amplification protocol (TRAP). The method developed offers a quick, simple and reproducible cellular-based assay for hTERT expression. This assay will provide a useful, new tool for future investigations, facilitating the analysis of hTERT expression in mixed cell populations.

Cell Differentiation↗

Receipt of psychotropic medication by people with intellectual disability in residential settings.

Previous studies have reported that the rate of prescription of antipsychotic medication for people with intellectual disability is far in excess of the expected prevalence of psychoses for this population. Recent research identifying factors which predict the use of psychotropic medication suggests that challenging behaviour may play a key role in determining the receipt of antipsychotic medication. The present study reports the prevalence of psychoactive medication receipt for 500 people with intellectual disability living in different forms of residential provision in the UK. Variables which predict the receipt of psychotropic medication are also identified. The results show differences between forms of residential provision in rates of medication receipt. Analyses of predictors of psychotropic medication receipt suggest that, whilst the receipt of antidepressants is predicted by symptoms of mental ill health, the receipt of both antipsychotics and hypnotics/anxiolytics is predicted by variables related to challenging behaviour.

Adult↗

Inhibition of aberrant and constitutive phosphorylation of the high-molecular-mass neurofilament subunit by CEP-1347 (KT7515), an inhibitor of the stress-activated protein kinase signaling pathway.

Previous studies have implicated stress-activated protein kinases (SAPKs) in aberrant phosphorylation of the high-molecular-mass neurofilament subunit (NFH). We now present direct evidence for this involvement using CEP-1347, a specific inhibitor of SAPK activation. Inhibition by this drug of stress-induced phosphorylation of NFH and the middle-molecular-mass neurofilament subunit in the perikaryon of dorsal root ganglion (DRG) neurons paralleled the decrease in levels of activated SAPKs and was essentially complete at 1 microM: CEP-1347. In addition, a role for SAPKs in the constitutive phosphorylation of NFH was demonstrated. Longterm treatment of unstressed DRG neurons with CEP-1347 lowered the steady-state phosphorylation level of NFH in neurites. No such effect was seen in neurons treated with PD 098059, which blocks activation of extracellular signal-regulated kinase 1/2. DRG neurites were shown to contain high basal levels of activated SAPKs. These included a 55-kDa SAPK whose activation was completely abolished at 0.05 microM: CEP-1347 and a 45-kDa SAPK that was not affected by the drug. These results indicate that SAPKs are involved in both stress-induced and constitutive phosphorylation of NFH. The differing responses of SAPKs in neurites and cell bodies to CEP-1347 inhibition further suggest the presence of different signaling pathways in the two neuronal compartments.

Animals↗

Plasmid DNA encoding influenza virus haemagglutinin induces Th1 cells and protection against respiratory infection despite its limited ability to generate antibody responses.

Direct intramuscular injection of plasmid DNA can generate immune responses against encoded antigens. However, the relative ability of DNA vaccines to induce cellular and humoral immunity after a single or booster immunization and the persistence of this response have not been fully elucidated. In this study, induction and maintenance of antibody and T cell subtypes with different doses of naked DNA encoding the haemagglutinin (HA) gene of influenza virus were examined and compared to the immune responses and protection induced by respiratory tract infection and immunization with a killed virus vaccine. Like natural infection, immunization with HA DNA induced potent Th1 responses. Spleen cells from mice immunized once with HA DNA in the dose range 10 ng to 100 microgram secreted significant levels of IFN-gamma, but low or undetectable IL-5, in response to influenza virus in vitro. Furthermore, CD4(+) HA-specific Th1 clones were generated from spleens of immunized mice. Although T cell responses waned 12 weeks after a single immunization, antigen-specific Th1 cells persisted in the spleen for at least 6 months after two booster immunizations. In contrast, influenza virus-specific ELISA IgG titres were low after a single immunization and required two booster immunizations to reach significant levels. Furthermore, haemagglutination inhibition (HI) antibodies were weak or undetectable after two immunizations. Nevertheless, two doses of HA DNA conferred almost complete protection against respiratory challenge with live virus. Thus, despite the limited ability to induce antibodies, DNA vaccines confer protective immunity against influenza virus infection, which appears to be mediated by Th1 cells.

Animals↗

A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis.

A European multicenter study of immunoblotting for the serodiagnosis of Lyme borreliosis showed considerable variation in results obtained from tests with a panel of 227 serum samples. Six laboratories used different immunoblot methods, and a wide range of bands was detected in all the assays. Multivariable logistic regression analysis of data from individual laboratories was used to determine the most discriminatory bands for reliable detection of antibodies to Borrelia burgdorferi sensu lato. These bands were used to construct individual interpretation rules for the immunoblots used in the six laboratories. Further analysis identified a subset of eight bands, which were important in all the laboratories, although with variations in significance. Possible European rules, all closely related, were formulated from these bands, although there was no single rule that gave high levels of sensitivity and specificity for all the laboratories. This is a reflection of the wide range of methodologies used, especially the use of different species and strains of B. burgdorferi sensu lato. The panel of European rules provides a framework for immunoblot interpretation which may be adapted in relation to the characteristics of Lyme borreliosis in local areas.

Antibodies, Bacterial↗

Reducing antipsychotic medication in people with a learning disability.

BACKGROUND: The use of antipsychotic drugs in people with learning disabilities is currently receiving intensified scrutiny and attempts are being made to reduce it. AIMS: A randomised controlled trial was designed to investigate factors influencing antipsychotic drug reduction among people with learning disabilities prescribed such medication for behavioural problems. METHOD: Thirty-six participants randomly allocated to the experimental group underwent four, monthly 25% drug reduction stages. There were no planned drug changes for the control group (n = 20). RESULTS: Twelve participants (33%) completed full withdrawal; a further seven (19%) achieved and maintained at least a 50% reduction. Drug reduction was associated with increased dyskinesia and higher activity engagement but not increased maladaptive behaviour. Some setting characteristics were associated with drug reinstatement. CONCLUSIONS: A substantial proportion of people with learning disability prescribed antipsychotic medications for behavioural purposes rather than for treating psychotic illness can have their drugs reduced or withdrawn.

Adult↗