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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 127 records · Page 7Linked to original sources
PubMed1999

Prospects for the treatment of endocrine-responsive tumours.

Much has been achieved over the last 30 years to improve the treatment of hormone-dependent cancer of the breast, ovary and prostate. The development of the antioestrogen tamoxifen (Nolvadex) spear-headed a range of drugs that counter the growth-promoting action of the female and male sex steroid hormones. An important additional benefit of endocrine therapies has been their low toxicity compared with conventional cancer chemotherapy thereby providing effective treatment with few serious side-effects and a sustained quality of life. Although some currently available therapies improve patient disease-free survival and overall survival, particularly when given in an adjuvant setting, they are not cures. There is, therefore, a continued need to develop newer therapies that extend the effectiveness of those currently available. This is particularly important when tumours either fail to respond or develop resistance to endocrine therapy. In this review, we examine how our improved understanding of the factors that influence the progression of endocrine-related tumours is leading to the development of novel therapies to treat both hormone-dependent and -independent tumours.

Animals↗
PubMed1999

An audit of measuring equipment in elderly care.

Accurate monitoring of weight and height is a vital element of nutritional assessment. Specialist equipment may be required for older patients. Accuracy depends upon calibration and maintenance of equipment.

Aged↗
PubMed1999

Experimental models of Parkinson's disease: insights from many models.

Toxin-induced and genetic experimental models have been invaluable in investigating idiopathic Parkinson's disease (PD). The neurotoxins--reserpine, 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and methamphetamine--have been used to develop parkinsonian models in a wide variety of species. Both 6-OHDA and MPTP can replicate the neurochemical, morphologic, and behavioral changes seen in human disease. The unilateral 6-OHDA rat model is an excellent model for testing and determining modes of action of new pharmacologic compounds. The nonhuman primate MPTP-induced parkinsonian model has behavioral features that best approximate idiopathic PD. These induced and genetic models have been used to study the pathophysiology of the degenerating nigrostriatal system and to evaluate novel therapeutic strategies. Important differences within these models provide insights into various aspects of the dopaminergic phenotype and its role as a target in disease. These models provide an avenue to evaluate many anti-parkinsonian compounds, such as levodopa, which was first evaluated in an animal model and is the gold standard of parkinsonian treatment today.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Glutamate Release from Chick Retina Explants in Response to Domoic Acid.

Release of endogenous glutamate (GLU) evoked by an exogenous excitotoxin such as kainate can contribute to central nervous system (CNS) excitotoxicity. In this study, the possibility that this mechanism accounts for reported domoic acid (DOM) toxicity was investigated using the isolated chick retina. Exposing retinas to 0-100 µM DOM for 40 min caused an increased efflux of lactate dehydrogenase (LDH) and a dose-related release of GLU into the incubation medium. Neuronal damage following exposure to DOM was confirmed by histologic examination of the retina. DOM-induced GLU release occurred at 27 and 37 degrees C and was more pronounced in medium containing a low calcium concentration (0.1 mM). In contrast, K(+) evoked GLU release occurred only at 37 degrees C in 2 mM calcium, but not at 27 degrees C. DOM-induced GLU release was reduced in hyperosmolar medium (medium 1 100 mM sucrose). Similar to GLU release, the LDH release occurred at both 27 and 37 degrees C and was reduced in hyperosmolar medium. These results suggest that an increase in membrane permeability secondary to osmotic swelling and lysis rather than a calcium-dependent vesicular exocytosis mechanism is responsible for GLU and LDH release. GYKI 52466, a selective noncompetitive antagonist of the non-NMDA receptor, prevented neuronal degeneration and GLU/LDH release. MK-801, a highly potent noncompetitive NMDA receptor blocker, reduced neuronal injury (33% decrease in LDH release), but did not reduce DOM-evoked GLU release significantly. Typical excitotoxic lesions were produced at all concentrations tested, with amacrine cells in the inner nuclear layer being the most severely affected. Released GLU contributed to further excitotoxic injury, exacerbating the neurotoxic action of DOM in isolated embryonic chick retina.

Journal Article↗
PubMed1999

An open-label trial of stavudine, lamivudine and efavirenz in the treatment of HIV-positive, treatment-naive patients, and implications for clinical practice.

A phase II, open-label study of stavudine, lamivudine and efavirenz resulted in significant reductions in plasma HIV-1 RNA over a 24 week period in human immunodeficiency virus (HIV)-infected individuals. The trial currently has 68 patients, and this presentation covers data on the first 42 patients enrolled for 24 weeks. The mean plasma HIV-1 RNA on entry was 75858 HIV RNA copies/ml, and the mean CD4 count was 380 cells/mm3. After 24 weeks, the CD4 count increased by 169 cells/mm3 above baseline. plasma HIV-1 RNA was markedly reduced: at 24 weeks, more than 97% of patients had <50 HIV RNA copies/ml based on observed data, and 89% of patients had <50 copies/ml based on strict intent-to-treat analysis (non-completer=failure). The favourable interactions of these agents resulted in no discontinuations owing to adverse effects. This regimen provides an important first-line treatment for antiretroviral-naive patients.

Adult↗
PubMed1998

Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor.

A new receptor for oxidized low-density lipoprotein (LDL), lectin-like oxidized LDL receptor-1 (LOX-1), has recently been cloned from bovine endothelial cells and human lung. A limited tissue-distribution study suggested that the protein was mainly produced by the vascular endothelium. In the present study we demonstrate that LOX-1 is also expressed in macrophages, where it may function as a scavenger receptor. LOX-1 was not detected in undifferentiated THP-1 cells or in freshly isolated human blood monocytes. However, mature human monocyte-derived macrophages and differentiated THP-1 cells showed high levels of LOX-1 transcripts. Consistent with these results, immunofluorescence staining and FACS analysis demonstrated that LOX-1 protein is expressed on the plasma membrane of macrophages. Western-blot analysis of membranes from macrophages (but not those from monocytes) identified a single band, with an apparent molecular mass of about 40 kDa, that displayed oxidized LDL-binding activity. These results suggest that differentiation induces the expression of LOX-1 in macrophages, where it may play a role as a scavenger receptor and/or a receptor for oxidized LDL.

Animals↗
PubMed1998

Systematic review of randomised controlled trials of interventions for painful shoulder: selection criteria, outcome assessment, and efficacy.

OBJECTIVE: To review the efficacy of common interventions for shoulder pain. DESIGN: All randomised controlled trials of non-steroidal anti-inflammatory drugs, intra-articular and subacromial glucocorticosteroid injection, oral glucocorticosteroid treatment, physiotherapy, manipulation under anaesthesia, hydrodilatation, and surgery for shoulder pain that were identified by computerised and hand searches of the literature and had a blinded assessment of outcome were included. MAIN OUTCOME MEASURES: Methodological quality (score out of 40), selection criteria, and outcome measures. Effect sizes were calculated and combined in a pooled analysis if study population, end point, and intervention were comparable. RESULTS: Thirty one trials met inclusion criteria. Mean methodological quality score was 16.8 (9.5-22). Selection criteria varied widely, even for the same diagnostic label. There was no uniformity in the outcome measures used, and their measurement properties were rarely reported. Effect sizes for individual trials were small (range -1.4 to 3.0). The results of only three studies investigating "rotator cuff tendinitis" could be pooled. The only positive finding was that subacromial steroid injection is better than placebo in improving the range of abduction (weighted difference between means 35 degrees (95% confidence interval 14 to 55)). CONCLUSIONS: There is little evidence to support or refute the efficacy of common interventions for shoulder pain. As well as the need for further well designed clinical trials, more research is needed to establish a uniform method of defining shoulder disorders and developing outcome measures which are valid, reliable, and responsive in affected people.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

A standardized protocol for measurement of range of movement of the shoulder using the Plurimeter-V inclinometer and assessment of its intrarater and interrater reliability.

OBJECTIVE: To develop a standardized protocol for measurement of shoulder movements using a gravity inclinometer designed for use in clinical trials, and to assess its intra- and interrater reliability in a group of manipulative physiotherapists. METHODS: After instruction, 6 manipulative physiotherapists independently assessed 8 movements of the shoulder, including total and glenohumeral flexion (TF, GHF), total and glenohumeral abduction (TA, GHA), external rotation in neutral (ERN) and abduction (ERA), internal rotation in abduction (IRA), and hand behind back (HBB), in random order in 6 patients with shoulder pain and stiffness according to a 6 x 6 Latin square design using the standardized protocol. The assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intra- and interrater reliability of the different movements varied widely. Reliability was higher for TF and TA than for the corresponding glenohumeral movements (e.g., intrarater ICCs: TF = 0.80, GHF = 0.65, TA = 0.75, GHA = 0.62). Interrater reliability was higher in the second round suggesting a practice effect (e.g., round 1, 2 interrater ICCs TF = 0.62, 0.82; TA = 0.62, 0.88; ERN = 0.85, 0.95). CONCLUSION: The measurement of the active range of TF, TA, ERN, and HBB, measured by manipulative physiotherapists following the standardized protocol, has intra- and interrater reliability acceptable for use as an outcome measure in clinical trials assessing interventions for shoulder pain.

Humans↗
PubMed1998

Changes in performance, muscle metabolites, enzymes and fibre types after short sprint training.

In contrast to endurance training, little research has been carried out to investigate the effects of short (< 10 s) sprint training on performance, muscle metabolism and fibre types. Nine fit male subjects performed a mean of 16 outdoor sprint running training sessions over 6 weeks. Distances sprinted were 30-80 m at 90-100% maximum speed and between 20 and 40 sprints were performed in each session. Endurance (maximal oxygen consumption; VO2max), sprint (10 m and 40 m times), sustained sprint (supramaximal treadmill run) and repeated sprint (6 x 40 m sprints, 24 s recovery between each) performance tests were performed before and after training. Muscle biopsy samples (vastus lateralis) were also taken to examine changes in metabolites, enzyme activities and fibre types. After training, significant improvements were seen in 40 m time (P < 0.01), supramaximal treadmill run time (P < 0.05), repeated sprint performance (P < 0.05) and VO2max (P < 0.01). Resting muscle concentrations of ATP and phosphocreatine did not change. Phosphorylase activity increased (P < 0.025), citrate synthase activity decreased (P < 0.01), but no significant changes were recorded in myokinase and phosphofructokinase activities. The proportion of type II muscle fibres increased significantly (P < 0.05). These results demonstrate that 6 weeks of short sprint training can improve endurance, sprint and repeated sprint ability in fit subjects. Increases in the proportion of type II muscle fibres are also possible with this type of training.

Adult↗
PubMed1998

Microplate-reverse hybridization method to determine dengue virus serotype.

A reverse transcriptase-polymerase chain reaction (RT-PCR) and microplate-reverse hybridization method were developed to detect and type dengue viruses in patients plasma specimens. A silica method was used to isolate RNA; and 3'-noncoding region universal primers were used to amplify dengue virus RNA. Using RT-PCR and ethidium bromide staining we could detect dengue virus in serum spiked with serially diluted dengue virus with a level of sensitivity similar to that of a quantitative fluorescent focus assay of dengue viruses in cell culture, i.e. 1.4 fluorescent focus units per reaction. Applying this assay to 14 dengue-positive plasma samples and 13 dengue-negative samples, dengue viremia was detectable by RT-PCR with a sensitivity comparable to mosquito inoculation. To determine the serotypes, digoxigenin-labeled PCR products from plasma samples and six laboratory adapted dengue viruses were hybridized in stringent conditions to serotype-specific DNA probes immobilized on microplates, and the hybridized product was detected with a colorimetric assay. Serotypes of dengue viruses, in cell culture and in patient plasma specimens, were identified using this method.

Dengue↗
PubMed1998

Correlation between intracellular cAMP content, kinematic parameters and hyperactivation of human spermatozoa after incubation with pentoxifylline.

Various compounds have been used in the attempt to improve sperm motility, including pentoxifylline (PF), a methylxanthine derivative. It has been postulated that PF, being a phosphodiesterase inhibitor, increases sperm kinematic parameters and the number of spermatozoa exhibiting hyperactivated motility by raising the intracellular content of cAMP, a molecule involved in the generation of sperm energy. However, it has not been clarified whether the biological effects of PF on sperm motility correlate with its ability to increase intracellular cAMP levels. To examine this relationship, the kinematic parameters, hyperactivation, and intracellular cAMP content were evaluated in motile spermatozoa, obtained by discontinuous Percoll gradient and swim-up from 21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and 4 h. PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after 1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The intracellular cAMP content of spermatozoa incubated with PF increased at all time-points examined. Both intracellular cAMP content and increase in hyperactivation in response to PF decreased with the length of incubation. In the absence of PF, cAMP content was unchanged and was correlated significantly only with ALH and the percentage of spermatozoa with hyperactivated motility. Following incubation with PF, cAMP content correlated with hyperactivation and all sperm kinematic parameters, with the exception of LIN and straightness. These findings suggest that the beneficial effects of PF on sperm kinematic parameters and hyperactivation are related to its ability to increase intracellular cAMP content.

Cyclic AMP↗
PubMed1998

Knowledge of and attitude toward patient confidentiality within three family medicine teaching units.

PURPOSE: To describe the knowledge and attitudes about confidentiality issues within family medicine teaching units (FMUs) at McGill University. METHOD: The authors surveyed McGill University FMU staff (physicians, nurses, and support staff) on their knowledge of and attitudes toward confidentiality issues. RESULTS: The response rate was 84%. Only one of nine questions on confidentiality laws was correctly answered by more than 80% of the respondents. Only 55% of the support staff knew that police are not permitted free access to charts, although the majority of those who answered incorrectly held attitudes that were consistent with the law. Only approximately 25% knew that physicians and nurses are not permitted free access to any medical record within the center. There were minimal differences between the professions or between the FMUs. CONCLUSION: These findings suggest that FMU staff do not fully understand their obligations towards patient confidentiality.

Attitude of Health Personnel↗
PubMed1998

The case history of an elite ultra-endurance cyclist who developed chronic fatigue syndrome.

An elite ultra-endurance athlete, who had previously undergone physiological and performance testing, developed chronic fatigue syndrome (CFS). An incremental cycling exercise test conducted while he was suffering from CFS indicated decreases in maximum workload achieved (Wmax; -11.3%), the maximum oxygen uptake (VO2max; -12.5%), and the anaerobic threshold (AT; -14.3%) compared to pre-CFS data. A third test conducted after the athlete had shown indications of significant improvement in his clinical condition revealed further decreases in Wmax (-7.9%), VO2max (-10.2%) and AT (-8.3%). These data, along with submaximal exercise data and muscle biopsy electron microscopic analyses, suggest that the performance decrements were the result of detraining, rather than an impairment of aerobic metabolism due to CFS per se. These data may be indicative of central, possibly neurological, factors influencing fatigue perception in CFS sufferers.

Adult↗
PubMed1998

In-phantom neutron fluence measurements in the orthogonal Birmingham boron neutron capture therapy beam.

This paper presents the results of an experimental investigation into the performance of the Birmingham accelerator-based epithermal BNCT beam. In-phantom gold foil activation and boron trifluoride tube measurements have been used. The results have been compared with calculated response rates using Monte Carlo modeling of the entire neutron system from source to phantom and detector. The excellent agreement obtained gives us confidence in the validity of the simulations and our ability to predict accurately the neutronic performance of our BNCT facility.

Biophysical Phenomena↗
PubMed1998

Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection.

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

CD4-Positive T-Lymphocytes↗
PubMed1998

Minimally oxidized low-density lipoprotein increases expression of scavenger receptor A, CD36, and macrosialin in resident mouse peritoneal macrophages.

Fully oxidized LDL (OxLDL) is believed to contribute to atherogenesis in part by virtue of uptake into macrophages via specific scavenger receptors. This phenomenon results in the formation of cholesterol-loaded foam cells, a major component of atherosclerotic lesions. The present study is directed at examining the effects of OxLDL and minimally oxidized LDL (MM-LDL) on scavenger receptor expression and activity in mouse peritoneal resident macrophages. Macrophages were preincubated with MM-LDL or OxLDL at concentrations of 25 or 50 microg/mL for 24 to 48 hours, after which their ability to bind and take up 125I-OxLDL or 125I-acetylated LDL (AcLDL) was determined. MM-LDL pretreatment induced a clear increase of cell association and degradation of 125I-OxLDL and 125I-AcLDL. Pretreatment with OxLDL also enhanced scavenger receptor activity, but to a lesser degree. Neither native LDL nor AcLDL had any effect. Scatchard analysis showed that preincubation with 50 microg/mL MM-LDL for 48 hours increased the Bmax of 125I-OxLDL and 125I-AcLDL by 139% and 154%, respectively, without significantly changing their affinity. Lipids extracted from MM-LDL also significantly induced scavenger receptor activity, but to a lesser extent than did intact MM-LDL. MM-LDL pretreatment increased both mRNA levels and protein levels of scavenger receptor A, CD36, and macrosialin. On the other hand, OxLDL pretreatment increased expression of macrosialin only. These results, showing that MM-LDL can upregulate scavenger receptor expression in mouse resident peritoneal macrophages, suggest that clearance of OxLDL by macrophages in lesions is more effective, in part because the OxLDL precursor, MM-LDL, primes the macrophage for foam cell generation.

Animals↗