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Biomedical subjects

L Ford

Publications and source records attributed to L Ford.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial.

BACKGROUND: Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism. METHODS: The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. RESULTS: All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg. CONCLUSION: In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia.

Adult↗
PubMed2005

A comparison of oral and intravenous bisphosphonate therapy for children with osteogenesis imperfecta.

Bone mineral density and fracture rates in children with osteogenesis imperfecta improve with intravenous bisphosphonates. The efficacy of oral bisphosphonates has not been established. This report is an analysis of an open-label, prospective, randomized clinical trial of oral compared to intravenous bisphosphonate medications in children with osteogenesis imperfecta. Children were stratified according to bone age, pubertal stage, and type of osteogenesis imperfecta and then randomized to receive intravenous pamidronate, 3 mg/kg over 3 days every 4 months, or oral alendronate 1 mg/kg, from a minimum of 10 mg to a maximum of 20 mg daily. The primary efficacy outcome was change in bone mineral density. Secondary outcomes included change in biomarkers of bone turnover, fracture incidence, and growth rate. Ten children were randomized (6 oral and 4 intravenous). Two other children were assigned to intravenous treatment due to chronic abdominal pain. In each group, three patients had type III/IV osteogenesis imperfecta, while three had type I. All 12 children completed 8 months of therapy; nine completed 12 months. Bone mineral density increased in both oral and intravenous groups equally and beyond that expected with normal growth. All children had a decrease in biochemical markers of bone turnover. Linear growth showed a moderate increase above that for age. There was a non-significant decrease in fracture incidence in both groups.

Administration, Oral↗
PubMed2004

Intravenous pamidronate treatment of children under 36 months of age with osteogenesis imperfecta.

INTRODUCTION: Bone mineral density (BMD) and fracture rates in children with osteogenesis imperfecta (OI) have been shown to improve with bisphosphonate therapy. There are limited data available on the efficacy of this therapy in children with OI under the age of 3 years. To examine this, we instituted a prospective clinical trial of intravenous bisphosphonate to study safety, feasibility, and efficacy of this therapy. MATERIALS AND METHODS: Nine infants and young children with osteogenesis imperfecta (age range 1-35 months) were treated with intravenous pamidronate. Six had type II OI, two had type I, and one had type IV. Pamidronate was administered in cycles of 3 consecutive days. The total duration of therapy ranged from 11 to 29 months (mean 17 months). RESULTS: During treatment, the mean annualized percent change in total body areal BMD was 25% (range 11-40%). Pamidronate therapy resulted in sustained and significant decreases in serum calcium and bone-specific alkaline phosphatase and in urine calcium/creatinine and NTX/creatinine. Fracture rate in the group decreased from 80 fractures in 111 months before treatment to 25 fractures in 152 months after treatment (P<0.01). Linear growth and weight gain were maintained. Other than fevers in several infants following the initial dose of intravenous bisphosphonate no adverse effects of therapy were noted. CONCLUSIONS: Our data support that intravenous pamidronate therapy is safe, increases BMD, and reduces fracture rates in very young children with OI. Currently, it would seem to be the best available treatment for these children.

Alkaline Phosphatase↗
PubMed2003

Accident and emergency and general practitioner plain radiograph reporting by radiographers and radiologists: a quasi-randomized controlled trial.

Two specially trained radiographers at York District Hospital have been reporting appendicular plain radiograph X-ray examinations for Accident and Emergency (A&E) patients since February 1995. This study explores the potential for further expanding their reporting role. This was achieved by assessing the two radiographers' and a group of consultant radiologists' ability to report on a retrospectively selected random stratified sample of 400 A&E and General Practitioner (GP) plain radiograph X-ray examinations for all body areas. Using receiver operating characteristic (ROC) curve analyses there was no statistically significant difference at the 5% level between the area under the ROC curves for the radiographers and consultant radiologists when reporting A&E or GP plain radiographs. It may be feasible to expand the reporting role of suitably trained radiographers to include plain radiograph X-ray examinations for all A&E patients and for GP patients, with no detriment to the quality of reports.

Clinical Competence↗
PubMed2001

Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial.

CONTEXT: Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)-positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown. OBJECTIVE: To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations. DESIGN, SETTING, AND PARTICIPANTS: Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999). MAIN OUTCOME MEASURE: Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo. RESULTS: Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive. CONCLUSION: Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.

Adult↗
PubMed2001

Effect of dietary cowpea trypsin inhibitor (CpTI) on the growth and development of the tomato moth Lacanobia oleracea (Lepidoptera: Noctuidae) and on the success of the gregarious ectoparasitoid Eulophus pennicornis (Hymenoptera: Eulophidae).

Cowpea trypsin inhibitor (CpTI) was shown to have a deleterious effect on the growth and development of larvae of the tomato moth, Lacanobia oleracea, when incorporated in artificial diet (2.0% of soluble protein) and expressed in transgenic potato leaf (up to 1.0% of soluble protein). The effect of CpTI on parasitism of L oleracea by the ectoparasitoid Eulophus pennicornis was investigated. The parasitic success of the wasp was reduced by the presence of CpTI in the diet of the host and, in the case of transgenic potato leaves expressing the transgene protein, was collated with the length of time the host fed on the diet prior to parasitism. In all cases the proportion of hosts parasitised when fed CpTI-containing diets was reduced when compared with controls, although these differences were only significant when hosts were fed from the third instar on the transgenic potato leaves. Parasitoid progeny that developed on L oleracea reared on CpTI-containing diets, however, were not adversely affected. These results show that, whilst expression of CpTI in transgenic potato plants confers resistance to the lepidopterous pest L oleracea, adverse effects on the ability of the ectoparasitoid E pennicornis to parasitise this moth species successfully may also occur. These results are discussed in relation to the potential impact of transgenic crops on beneficial biological control agents.

Animals↗
PubMed2001

Influence of plant development and environment on transgene expression in potato and consequences for insect resistance.

Clonal replicates of different transformed potato plants expressing transgene constructs containing the constitutive Cauliflower Mosaic Virus (CaMV) 35S promoter, and sequences encoding the plant defensive proteins snowdrop lectin (Galanthus nivalis agglutinin; GNA), and bean chitinase (BCH) were propagated in tissue culture. Plants were grown to maturity, at first under controlled environmental conditions, and later in the glasshouse. For a given transgene product, protein accumulation was found to vary between the different lines of clonal replicates (where each line was derived from a single primary transformant plant), as expected. However, variability was also found to exist within each line of clonal replicates, comparable to the variation of mean expression levels observed between the different clonal lines. Levels of GNA, accumulated in different parts of a transgenic potato plant, also showed variation but to a lesser extent than plant-plant variation in expression. With the majority of the clonal lines investigated, accumulation of the transgene product was found to increase as the potato plant developed, with maximum levels found in mature plants. The variation in accumulation of GNA among transgenic plants within a line of clonal replicates was exploited to demonstrate that the enhanced resistance towards larvae of the tomato moth, Lacanobia oleracea L., caused by expression of this protein in potato, was directly correlated with the level of GNA present in the plants, and that conditions under which the plants were grown affect the levels of GNA expression and subsequent levels of insect resistance.

Animals↗
PubMed2001

HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse.

Human leukocyte antigens (HLA) class I molecules restrict the interaction between cytotoxic T cells and target cells. Abnormalities in HLA class I antigen expression and/or function may provide tumor cells with a mechanism for escaping immune surveillance and resisting T cell-based immunotherapies. The potential for applying T cell-based immunotherapy in the treatment of acute myeloid leukemia (AML) has stimulated interest in analyzing HLA class I antigen expression on leukemic blasts in this disease. Little information is available in the literature. We have analyzed HLA class I antigen expression on bone marrow samples from 25 newly diagnosed AML patients by indirect immunofluorescence staining with monoclonal antibodies. Five of these patients were also studied at relapse. Leukemic blasts were resolved from normal lymphocytes by staining with antiCD45 antibody; CD45 expression is dim on leukemia cells, but bright on lymphocytes. HLA class I antigen expression was higher on leukemic blasts than on autologous lymphocytes in all but one case. Moreover, there was no significant change in HLA class I antigen expression at relapse. These results suggest that abnormalities in HLA class I antigens are infrequent in AML and should not represent a major obstacle to the application of T cell-based immunotherapies in this disease.

Acute Disease↗
PubMed2001

Wolbachia bacteria in filarial immunity and disease.

Lymphatic filarial nematodes are infected with endosymbiotic Wolbachia bacteria. Lipopolysaccharide from these bacteria is the major activator of innate inflammatory responses induced directly by the parasite. Here, we propose a mechanism by which Wolbachia initiates acute inflammatory responses associated with death of parasites, leading to acute filarial lymphangitis and adverse reactions to antifilarial chemotherapy. We also speculate that repeated exposure to acute inflammatory responses and the chronic release of bacteria, results in damage to infected lymphatics and desensitization of the innate immune system. These events will result in an increased susceptibility to opportunistic infections, which cause acute dermatolymphangitis associated with lymphoedema and elephantiasis. The recognition of the contribution of endosymbiotic bacteria to filarial disease could be exploited for clinical intervention by the targeting of bacteria with antibiotics in an attempt to reduce the development of filarial pathology.

Animals↗
PubMed2000

Snowdrop lectin (GNA) has no acute toxic effects on a beneficial insect predator, the 2-spot ladybird (Adalia bipunctata L.).

Two-spot ladybird (Adalia bipunctata L.) larvae were fed on aphids (Myzus persicae (Sulz.)) which had been loaded with snowdrop lectin (Galanthus nivalis agglutinin; GNA) by feeding on artificial diet containing the protein. Treatment with GNA significantly decreased the growth of aphids. No acute toxicity of GNA-containing aphids towards the ladybird larvae was observed, although there were small effects on development. When fed a fixed number of aphids, larvae exposed to GNA spent longer in the 4th instar, taking 6 extra days to reach pupation; however, retardation of development was not observed in ladybird larvae fed equal weights of aphids. Ladybird larvae fed GNA-containing aphids were found to be 8-15% smaller than controls, but ate a significantly greater number of aphids (approx. 40% to pupation). GNA was shown to be present on the microvilli of the midgut brush border membrane and within gut epithelial cells in ladybird larvae fed on GNA-dosed aphids, although disruption of the brush border was not observed. It is hypothesised that GNA does not have significant direct toxic or adverse effects on developing ladybird larvae, but that the effects observed may be due to the fact that the aphids fed on GNA are compromised and are thus a suboptimal food.

Journal Article↗
PubMed2000

The Fort McMurray Demonstration Project in Social Marketing: theory, design, and evaluation.

CONTEXT: The Fort McMurray Demonstration Project in Social Marketing is a multifaceted program that applies the techniques of social marketing to health and safety. This paper describes the origins of the project and the principles on which it was based. VENUE: Fort McMurray, in the province of Alberta, Canada, was selected because the community had several community initiatives already underway and the project had the opportunity to demonstrate "value added." CONCEPT: The project is distinguished from others by a model that attempts to achieve mutually reinforcing effects from social marketing in the community as a whole and from workplace safety promotion in particular. DESIGN: Specific interventions sponsored by the project include a media campaign on cable television, public activities in local schools, a community safety audit, and media appearance by a mascot that provides visual identity to the project, a dinosaur named "Safetysaurus." The project integrated its activities with other community initiatives. MAIN OUTCOME MEASURES: The evaluation component emphasizes outcome measures. A final evaluation based on injury rates and attitudinal surveys is underway. RESULTS: Baseline data from the first round of surveys have been compiled and published. In 1995, Fort McMurray became the first city in North America to be given membership in the World Health Organization's Safe Community Network.

Adult↗
PubMed1999

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

Aged↗
PubMed1999

Release of cardiac troponin in acute coronary syndromes: ischemia or necrosis?

Analysis of cardiac troponin T and I have been shown to be effective in detecting minor myocardial injury in cardiac patients who present with acute coronary syndromes (ACS). Determination of minor myocardial injury is significant, as these patients have a higher short-term morbidity and mortality than other unstable angina patients with normal concentrations for these markers. In this report, two theories are given as to why cardiac troponin is superior to other markers such as CK-MB for risk stratification. The 'low cut-off concentration model' is based on the fact that troponin is not increased in patients with skeletal muscle disease or injury, resulting in low baseline concentrations of the cardiac isoforms in the absence of active cardiac disease. This enables the use of low decision limits. Troponin also has a higher myocardial tissue content relative to CK-MB, thereby also increasing its clinical sensitivity to irreversible injury. In the 'reversible ischemia model', cytoplasmic free troponin T and I leak across the membrane of myocytes as the result of reduced coronary blood flow. Jeopardized myocardial tissue can recover with acute recanalization. Support for this model comes from clinical observations and animal studies.

Biomarkers↗
PubMed1999

A proteomic analysis of erythromycin resistance in Streptococcus pneumoniae.

Streptococcus pneumoniae is a significant human pathogen which is an important cause of pneumonia and bacteraemia. Over the past few years the incidence of antibiotic resistance among clinical isolates of S. pneumoniae has increased. Penicillin resistance is now widespread and the frequency of isolates that are resistant to erythromycin has risen. Erythromycin resistance in S. pneumoniae follows two basic patterns. The MLS erythromycin-resistant phenotype is due to the enzymatic methylation of ribosomal RNA that blocks erythromycin binding to the ribosome. Alternatively, in isolates of the M phenotype, a more recently documented mechanism, resistance is associated with an active efflux process that reduces intracellular levels of erythromycin. We used two-dimensional electrophoresis to examine the proteins synthesised by erythromycin-susceptible and -resistant S. pneumoniae. Erythromycin-resistant S. pneumoniae with the M phenotype showed a significantly increased synthesis of a 38,500 Dalton (pI 6.27) protein compared to susceptible isolates. Peptide mass mapping was used to identify the 38,500 Dalton protein as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It was demonstrated that S. pneumoniae synthesised at least three forms of GAPDH that differed in their isoelectric points. The form of GAPDH possessing the most basic pI showed the increased synthesis in the erythromycin-resistant S. pneumoniae isolates. Alterations in the synthesis of GAPDH were only found for those erythromycin-resistant isolates possessing the M phenotype. S. pneumoniae isolates with the MLS phenotype were indistinguishable from the susceptible strains using the analytical conditions employed for the current study. The possible role of GAPDH in erythromycin resistance of S. pneumoniae is considered.

Anti-Bacterial Agents↗
PubMed1999

Protease activity in the larval stage of the parasitoid wasp, Eulophus pennicornis (Nees) (Hymenoptera: Eulophidae); effects of protease inhibitors.

Hymenopteran, parasitoid wasps have good potential for use in integrated pest management (IPM); for example, the gregarious ectoparasitoid, Eulophus pennicornis, has been suggested as a biological control agent for larvae of the tomato moth (Lacanobia oleracea L.). However, the processes by which such parasitic larvae are able to utilize the nutritional resource provided by the host have been little studied. Protease activity was present in E. pennicornis larvae, and characterization of the enzymes responsible for proteolysis was performed using a range of synthetic substrates and specific inhibitors. Serine protease enzymes was both trypsin- and chymotrypsin-like activities were present. A range of plant-derived serine protease inhibitors was tested for activity against these enzymes. Certain inhibitors, notably soybean Kunitz inhibitor (SKTI), inhibited enzyme activity by > 80% at < 10(-5) M. When SKTI was fed to L. oleracea larvae in an artificial diet, the inhibitor was subsequently detected within the larval haemolymph, showing that protease inhibitors in the host diet can be delivered to a parasitoid via the host haemolymph. If transgenic plants expressing foreign protease inhibitors for protection against insect pests are to form a component of IPM systems, possible adverse effects, whether direct or indirect, of transgene expression on parasitoids like E. pennicornis should be considered.

Animals↗
PubMed1998

Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.

BACKGROUND: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992. METHODS: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. RESULTS: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. CONCLUSIONS: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.

Adult↗