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Biomedical subjects

P Gill

Publications and source records attributed to P Gill.

At least 55 records · Page 3Linked to original sources
PubMed2000

Improving detection of venous thromboembolism. New technology holds promise for early, precise diagnosis.

In recent years, a number of modalities have been evaluated for the diagnosis of venous thromboembolism. The role of these modalities is still evolving. While ventilation-perfusion scanning is important in the diagnosis of venous thromboembolism, spiral CT scanning, MRI, and D-dimer assays are now being used more often, either exclusively or in combination with ventilation-perfusion scanning. A number of diagnostic algorithms using these modalities are currently being evaluated. Regardless of which diagnostic approach is used, the clinician must be aware of some key limitations. Spiral CT scanning has gained popularity because it is noninvasive and can rapidly identify other cardiopulmonary diseases that mimic pulmonary embolism. Its use has been limited because of its inability to detect subsegmental pulmonary emboli. D-dimer assays offer promise as rapid, inexpensive screening tools. However, the wide variability in assay performance has limited its usefulness. We recommend that if D-dimer assays are to be used in a diagnostic algorithm, the clinician be aware of the details of the assay. At present, lack of data precludes use of MRI as a primary diagnostic tool for detection of venous thromboembolism.

Fibrin Fibrinogen Degradation Products↗
PubMed2000

Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma.

Because human herpesvirus-8 (HHV-8) DNA has been found in multiple myeloma (MM) patients by polymerase chain reaction, it was suggested that HHV-8 may play a role in the transformation of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore, 362 MGUS sera with and without progression to MM were tested for IgG antibody to HHV-8. Only 7.8% of the MGUS sera contained HHV-8 antibody to lytic proteins, and IgG antibody to HHV-8 latent antigen was even lower than lytic antibody (2.9%). No differences were observed in the distribution of antibody to HHV-8 in sera from MGUS patients who progressed to MM. The seroprevalences of HHV-8 in MGUS (7.8%), MM (5.4%), and healthy donors (5.9%) were similar, thus arguing for the lack of epidemiologic evidence of HHV-8 participation in the pathogenesis of MM. MGUS patients were immune competent in response to Epstein-Barr virus (EBV) infection because 97% contained antibody to EBV virus capsid antigen.

Herpesvirus 8, Human↗
PubMed2000

An investigation of the rigor of interpretation rules for STRs derived from less than 100 pg of DNA.

By increasing the PCR amplification regime to 34 cycles, we have demonstrated that it is possible routinely to analyse <100 pg DNA. The success rate was not improved (without impairing quality) by increasing cycle number further. Compared to amplification of 1 ng DNA at 28 cycles, it was shown that increased imbalance of heterozygotes occurred, along with an increase in the size (peak area) of stutters. The analysis of mixtures by peak area measurement becomes increasingly difficult as the sample size is reduced. Laboratory-based contamination cannot be completely avoided, even when analysis is carried out under stringent conditions of cleanliness. A set of guidelines that utilises duplication of results to interpret profiles originating from picogram levels of DNA is introduced. We demonstrate that the duplication guideline is robust by applying a statistical theory that models three key parameters - namely the incidence of allele drop-out, laboratory contamination and stutter. The advantage of the model is that the critical levels for each parameter can be calculated. This information may be used (for example) to determine levels of contamination that can be tolerated within the strategy employed. In addition we demonstrate that interpreting one banded loci, where allele dropout could have occurred, using LR=1/2f(a) was conservative provided that the band was low in peak area. Furthermore, we demonstrate that an apparent mis-match between crime-stain and a suspect DNA profile does not necessarily result in an exclusion. The method used is complex, yet can be converted into an expert system. We envisage this to be the next step.

Alleles↗
PubMed2000

Synthesis and pharmacology of new enantiopure delta(3)-4-arylkainoids.

Seven delta(3)-4-arylkainoids possessing various 4-position aromatic and heteroaromatic groups were synthesized and their apparent affinities were measured in order to explore the influences of 4-position electron density and stereochemistry on receptor affinity and specificity. Kainoids 1a-f were shown to be selective agonists at the NMDA receptor and the electron rich furanyl and thienyl analogues exhibited the highest affinities. Naphthylkainoid 1g proved to be a nonselective antagonist at the iGluRs.

Excitatory Amino Acid Agonists↗
PubMed2000

Report of the European Network of Forensic Science Institutes (ENSFI): formulation and testing of principles to evaluate STR multiplexes.

This paper describes a collaborative exercise organised under the auspices of the European Network of Forensic Science Institutes (ENFSI). The purpose of this EU (European Union) funded group is to carry out research to enable STR loci to be compared between European laboratories, ultimately leading to the formation of a pan-European database. Accordingly, an exercise was designed to evaluate a prototype STR multiplex system manufactured by Applied Biosystems (ABD). Each laboratory was sent 12 samples to analyse along with a multiplex kit. Of specific interest was the definition of parameters to define the efficiency of the system. Stutter, split allelic peaks (differing by one base), pull-up, heterozygous balance and between locus balance were all objectively measured. Once the important parameters are defined it is possible to directly compare performances of different multiplexes and the different laboratories carrying out the tests. Since the multiplex used was a prototype system, this exercise cannot be regarded as a proficiency test.

Alleles↗
PubMed2000

Phase I dose escalation pharmacokinetics of O-(chloroacetylcarbamoyl) fumagillol (TNP-470) and its metabolites in AIDS patients with Kaposi's sarcoma.

The pharmacokinetics of TNP-470 and its major metabolites were investigated in AIDS patients enrolled in a phase I dose escalation trial for the treatment of Kaposi's sarcoma. The patients received TNP-470 by 1-h intravenous infusion in dose cohorts of 10, 20, 30, 40, 50 and 70 mg/m2. The parent drug and metabolites, MII and MIV, were measured by high-performance liquid chromatography/mass spectrometry (HPLC/MS) in plasma samples collected during and out to 168 h after the beginning of the infusion. Both metabolites were detected in all patients' plasma, while the parent drug was undetectable at time-points as early as 5 min after the end of infusion for some patients. A large interpatient variability of pharmacokinetic parameters among the dosing cohorts was observed for TNP-470, with a mean (+/- SD) plasma elimination half-life (t1/2) of 0.06 +/- 0.04 h, plasma clearance (CL) of 1487 +/- 1216 l/h and an area under the concentration versus time curve (AUC) of 49.9 +/- 35.8 ng/ml x h. Time to maximum plasma concentration (Tmax) typically occurred before the end of the infusion. The predominant plasma metabolite was MII with a t1/2 of 1.21 +/- 0.43 h, AUC of 1226 +/- 2303 l/h and a Tmax occurring between 5 and 15 min after infusion. The reported active metabolite MIV had a t1/2 of 0.24 +/- 0.13 h, AUC of 24.9 +/- 32.6 ng/ml x h and a Tmax occurring between the midpoint of the infusion and 15 min after infusion. The parent drug was undetectable by HPLC/MS/MS in urine samples collected and pooled between 0-6 and 6-24 h from the beginning of drug administration. Metabolite MIV was present in the 0-6-h urine pool of two patients enrolled in the highest dosing cohorts, equivalent to 0.4% of the administered dose. Metabolite MII was present in all 0-6-h samples analyzed and represented 1.12 +/- 0.9% of the administered dose. Renal clearance (CLR) for MII was 140 +/- 70 ml/h.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Team nursing and ITU--a good combination?

Deficits in 'measurable care', in an 11-bedded intensive care unit, prompted a pilot study of team nursing. Team nursing was introduced for three beds out of the total 11 for a period of six months. In order to evaluate the effects, aspects of care and job satisfaction were measured and compared between the team nursing beds and the rest of the unit. The study revealed that job satisfaction and the levels of 'measurable care' did not improve whilst team nursing was practised. Based on this evidence, the authors question the relevance of team nursing in this particular intensive therapy unit (ITU) and maintain that the best method of delivering nursing care in ITU remains unclear.

Attitude of Health Personnel↗
PubMed2000

Socio-economic characteristics of adult frequent attenders in general practice: secondary analysis of data.

OBJECTIVE: This study was carried out to determine the effect of a range of socio-economic features on frequent attendance in general practice from a large database of general practice consultations using two definitions of frequent attendance. METHODS: Secondary analyses were carried out of data from the Fourth National Survey of Morbidity in General Practice covering 60 general practices in England and Wales. A total of 283 842 adult patients and their consultations between September 1991 and August 1992 were examined. The main outcome measure was the odds ratio of being a frequent attender (95% confidence intervals). RESULTS: Using a definition of 12+ consultations/year, men were less likely to be frequent attenders (OR 0.14, 95% CI 0.13-0.17); however, the difference between men and women lessens with age. Patients who were more likely to be frequent attenders included those who were divorced or widowed (1.41, 1.31-1.51); from social classes IIIM (1.23, 1.17-1.29) and IV/V (1.33, 1.26-1.41); South Asian people (1.38, 1.16-1.65); or unemployed (1.61, 1.46-1.77). Other factors signifying isolation or poverty were also linked to frequent attendance. Using the definition of '6+ consultations for minor problems' produced broadly similar results although the relative weight of the factors showed some differences. CONCLUSIONS: Socio-economic factors were important indicators of frequent attendance in general practice. Results were very similar using either definition, suggesting that both are valid for further work. Furthermore, frequent attendance is a complex process associated with many factors outside the control of the GP.

Adolescent↗
PubMed2000

Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage.

The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.p.i.). The distribution of inflammation and chemokine production in cryolesion-EAE and EAE-only were compared. Inflammation in the brain, measured by immunocytochemistry for T lymphocytes (W3/13) and microglial activation (MHC class II -OX6), was significantly enhanced in cryolesion-EAE 11-15 d.p.i. (p < 0.01-0.05) but by 20-40 d.p.i., equated with EAE-only. Inflammation in cryolesion-EAE related to breakdown of the blood-brain barrier (BBB) at the site of the cryolesion and also to the corticospinal tracts and thalamus, reflecting the afferent and efferent neuronal connections with the cryolesioned cortex. Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha. By 14 d.p.i., the levels of MCP-1 and MCP-5 mRNA equated with EAE-only animals. These results suggest that enhancement and location of autoimmune inflammation in the brain following focal cortical injury initially involve chemokines such as the macrophage chemoattractants MCP-1 and MCP-5, and the activities of afferent and efferent neuronal connections with the site of damage. By analogy, similar factors may modulate or reactivate autoimmune inflammation in MS.

Animals↗
PubMed2000

Prevalence of GBV-C/hepatitis G virus viremia and anti-E2 in Canadian blood donors.

BACKGROUND AND OBJECTIVES: GB virus C (GBV-C)/hepatitis G virus (HGV) is a recently recognized parenterally and sexually transmitted agent. The prevalence of GBV-C/HGV markers in Canadian blood donors has not been previously studied and was therefore determined. MATERIALS AND METHODS: Blood donors [identity unlinked (IU), short-term temporarily deferred (STTD) and autologous groups] and donor samples with antibodies to hepatitis C (anti-HCV) or hepatitis B core were tested for GBV-C/HGV RNA and for antibodies to E2 antigen (anti-E2). RESULTS: GBV-C/HGV RNA was found in 1.1% and anti-E2 in 7.3% of the combined IU/STTD donor group. Viremia was much more common in anti-HCV-positive samples (12.5%); anti-E2 was present in >50% of this group. In the STTD group, female gender was significantly associated with viremia. CONCLUSION: GBV-C/HGV infection is relatively common in Canadian donors, and a small proportion are viremic. The association of female gender and viremia was unexpected. Further study is needed to clarify the epidemiology and natural history of GBV-C/HGV infection.

Adolescent↗
PubMed2000

Selective killing of RPE with a vascular endothelial growth factor chimeric toxin.

PURPOSE: To determine the sensitivity of retinal pigment epithelial (RPE) cells to a vascular endothelial growth factor (VEGF) chimeric toxin. METHODS: A targeted toxin was developed using recombinant methods to fuse VEGF165 to the diphtheria toxin (DT) translocation and enzymatic domain (DT390-VEGF165). Human RPE cells, choroidal endothelial cells (CECs), and scleral fibroblasts were isolated, and a dose-response for DT390-VEGF165 was determined by measurement of cell proliferation and cell number. In parallel experiments, cultures were pretreated with transforming growth factor (TGF)-beta2. VEGF-receptor (VEGFR-1 and -2) expression was determined using reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting, and affinity was measured using Scatchard analysis. RESULTS: RPE cells and CECs were similarly prone to killing by the VEGF-toxin, but scleral fibroblasts were unaffected. Pretreatment with TGF-beta2 selectively increased the sensitivity of RPE cells to the VEGF-toxin. RPE cells expressed both VEGFR-1 and -2 in vitro; however, the expression of VEGFR-1 was very low. Pretreatment with TGF-beta2 (10 ng/ml) was associated with increased expression of the VEGFR-1 in RPE cells and increased receptor affinity for VEGF detected by Scatchard analysis. CONCLUSIONS: Dose-dependent killing of RPE cells by the DT390-VEGF165 conjugate is selectively enhanced by pretreatment with TGF-beta2. This study provides further strong support for the presence of functional VEGFRs on human RPE cells, and demonstrates for the first time the ability to target a normal nonendothelial cell type through VEGFR expression.

Cell Division↗
PubMed1999

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa.

Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.

Adolescent↗