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Biomedical subjects

J Shaw

Publications and source records attributed to J Shaw.

At least 73 records · Page 4Linked to original sources
PubMed2000

Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black.

Ultrafine particles have been shown to induce pro-inflammatory effects both in vivo and in vitro. Increased expression of pro-inflammatory genes probably requires the activation of specific transcription factors such as nuclear factor kappa B (NF-kappaB) via a number of possible pathways including Ca2+ and reactive oxygen species. The fluorescent dye fura 2, was used to measure cytosolic Ca2+ in the human monocytic cell line, Monomac 6 on exposure to 66 microg x mL(-1) of either ultrafine carbon black (ufCB; diameter 14 nm), carbon black (CB; diameter 260 nm), quartz (diameter 1.45 microm), or medium alone. UfCB but not fine CB induced a 1.6-fold increase (p<0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. In addition ufCB induced a 2.6-fold increase (p<0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. This response was inhibited by the removal of extracellular Ca2+ and by the Ca2+ channel blocker, verapamil. In addition, ufCB stimulated the entry of extracellular Mn2+. Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. The particles may in part activate the opening of Ca2+ channels via a mechanism involving reactive oxygen species.

Calcium↗
PubMed2000

Proteomic analysis of differential protein expression in primary hepatocytes induced by EGF, tumour necrosis factor alpha or the peroxisome proliferator nafenopin.

Peroxisome proliferators are nongenotoxic rodent-liver carcinogens that have been shown to cause both an induction of hepatocyte proliferation and a suppression of apoptosis. Both epidermal growth factor (EGF) and the peroxisome proliferator nafenopin induce DNA replication in primary rat hepatocyte cultures, but apparently through different signalling pathways. However, both EGF and nafenopin require tumour necrosis factor alpha (TNFalpha) signalling to induce DNA replication. By examining proteins isolated from rat primary hepatocyte cultures using two-dimensional gel electrophoresis and mass spectrometry, we found that proteins showing an altered expression pattern in response to nafenopin differed from those showing altered expression in response to EGF. However, many proteins showing altered expression upon stimulation with TNFalpha were common to both the EGF and nafenopin responses. These proteome profiling experiments contribute to a better understanding of the molecular mechanisms involved in the response to peroxisome proliferators. We found 32 proteins with altered expression upon stimulation with nafenopin, including muscarinic acetylcholine receptor 3, intermediate filament vimentin and the beta subunit of the ATP synthase. These nonperoxisomal protein targets offer insights into the mechanisms of peroxisome proliferator-induced carcinogenesis in rodents and provide opportunities to identify toxicological markers to facilitate early identification of nongenotoxic carcinogens.

Actins↗
PubMed2000

Neuropsychological predictors of distress following traumatic brain injury.

Emotional and behavioural difficulties are one of the most common difficulties following traumatic brain injury (TBI), although it is not clear which individuals with TBI become most distressed. Numerous factors contribute to adjustment following TBI, and the current study examined degree of cognitive decline as one potential contributor to distress following TBI. The relationship between cognitive functioning and distress may be conceptualized as being related to (a) an individual's absolute level of cognitive ability following TBI, or (b) relative degree of decline following TBI (i.e. the greater the decline, the greater the distress, regardless of absolute level of ability). The current study tested these hypotheses by comparing a measure of global emotional distress with measures of absolute level of neuropsychological functioning and indices of cognitive decline. In contrast to hypotheses, regression analyses indicated that estimated pre-morbid ability accounted for more variance in distress following TBI than either absolute level of functioning or indices of cognitive decline, with individuals with higher estimated pre-morbid abilities reporting lower levels of distress. Treatment implications are discussed.

Adolescent↗
PubMed2000

Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy.

Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.

2-Aminopurine↗
PubMed2000

Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient.

BACKGROUND: In many transplant centres lamivudine is an important component of prophylaxis against, and treatment of, hepatitis B virus (HBV) graft infection. Drug resistant HBV species with specific polymerase mutations may emerge during lamivudine treatment. AIMS: To examine the clinical consequences of graft infection by lamivudine resistant virus. METHODS: The clinical course of four liver transplant patients who developed graft infection with lamivudine resistant virus was reviewed. The response of HBV infection to reduction of immunosuppression and to manipulation of antiviral therapy was assessed. For each patient, serum viral titre was measured and the viral polymerase gene was sequenced at multiple time points. RESULTS: High serum titres were observed following emergence of the lamivudine resistant species. Wild type HBV re-emerged as the dominant serum species after lamivudine withdrawal. All patients developed liver failure, and onset of liver dysfunction was observed when resistant virus was the dominant serum species. In three patients, liver recovery was observed when immunosuppression was stopped and when alternative antivirals were given. Wild type virus appeared to respond to ganciclovir, and to reintroduction of lamivudine. For one patient, introduction of famciclovir was associated with clinical, virological, and histological response. CONCLUSIONS: Failure of lamivudine prophylaxis may identify patients at special risk for the development of severe graft infection. Treatment of graft reinfection should include reduction of immunosuppression, and systematic exposure to alternative antivirals. Viral quantitation and genetic sequencing are essential components of therapeutic monitoring.

Adult↗
PubMed2000

Automated measurement of unsaturated iron binding capacity is an effective screening strategy for C282Y homozygous haemochromatosis.

BACKGROUND: C282Y hereditary haemochromatosis is an appropriate condition for population screening. Transferrin saturation, the best screening test to date, is relatively expensive, labour intensive, and cannot be automated. Unsaturated iron binding capacity is a surrogate marker of transferrin saturation and its measurement can be automated. AIMS: To evaluate a screening strategy for C282Y hereditary haemochromatosis in a tertiary hospital environment based on unsaturated iron binding capacity as the initial screening test. METHODS: Measurement of unsaturated iron binding capacity was adapted to the main laboratory analyser. An unsaturated iron binding capacity of less than 30 micromol/l was identified as an appropriate decision point and 5182 consecutive subjects were screened over 28 consecutive days. RESULTS: Of those screened, 697 had an unsaturated iron binding capacity less than 30 micromol/l. Of these, transferrin saturation was greater than 40% in 294. A total of 227 were able to be genotyped for the C282Y mutation. Nine subjects homozygous for C282Y were identified. Based on full cost recovery, affected persons were identified at a cost of Aus$2268.77 per case (approximately US$1496). CONCLUSION: Automated measurement of unsaturated iron binding capacity enables a cost effective, large scale population screening programme for C282Y hereditary haemochromatosis to be developed.

Adult↗
PubMed2000

Circadian rhythms in Neurospora: a new measurement, the reset zone.

The authors define a new feature of a circadian rhythm, the reset zone, and point out its usefulness for predictions concerning oscillator behavior. The reset zone measures the responses of a circadian system to resetting pulses. It can be easily determined from a phase transition curve (PTC), which is simply a phase response curve (PRC) replotted as new phase versus old phase (Winfree's format). The reset zone is the range of new phases seen in such a plot and has two potentially useful characteristics: its size and its midpoint. A series of experiments with Neurospora involving temperature pulses indicated that the size of the reset zone changed in a nonlinear way in response to both the duration of 40 degrees C pulses and to the magnitude of temperature change for 3-h pulses. Other existing data are replotted to show how the reset zone size varies with growth temperature and with the period of different clock mutants. Employing exclusively reset zone data within the framework of a limit cycle displacement model, an equation is formulated that predicts the relative changes in the values of state variables of the oscillator for changes in any given environmental condition, such as temperature. Examples are also drawn from other organisms, such as hamsters, Gonyalaux, Kalanchoe, and Drosophila, illustrating the usefulness of the reset zone measurement. It can be used as a numerical scale for assessing the strength of a pulse, for comparing the relative effects of a given pulse applied to different organisms or mutants, for determining the directionality of the changes in state variables produced by various types of pulses, and possibly for measuring clock amplitude.

Circadian Rhythm↗
PubMed2000

Developing a multidisciplinary complex wound care service.

This article will describe the development of a dedicated multidisciplinary complex/chronic wound care service. Using a recognized framework, the article will demonstrate how the needs of patients were first assessed and then addressed. The article will conclude that although more research is required, the results of this audit suggest that patients with long-standing complex/chronic wounds benefit from the care of a dedicated multidisciplinary wound care team. For the purpose of this article the term 'complex' is defined as any wound which is not progressing as expected despite the application of good quality standard wound care.

Chronic Disease↗
PubMed2000

Efficacy and safety of direct stenting in coronary angioplasty.

BACKGROUND: Direct stenting is the deployment of an intracoronary stent without lesion predilation. Potential advantages include shorter procedural time, lower contrast dose and reduced spiral dissections. There is also the potential financial benefit of less balloon and/or stent usage. Concern still exists among some operators, however, regarding failure of stent deployment and local complications. METHODS: Of 467 consecutive angioplasty cases at the Alfred Hospital between August 1, 1997 and May 22, 1998, direct stenting was attempted in 93 patients (20%). Interventionalist preference determined whether direct stenting was attempted. Vessels with excessive calcification, severe proximal tortuosity or small caliber were typically considered unsuitable for direct stenting. RESULTS: A total of 102 lesions (38 type A, 60 type B, and 4 type C) were treated with direct stenting. Initial deployment was successful in 98 of 102 lesions, with a further 3 lesions successfully stented following predilation. A stent was unable to be deployed in only 1 case; however, the lesion was treated with balloon angioplasty alone. The majority of lesions required only 1 stent (an average of 1.1 stents were used per lesion). Distal complications occurred in 5 patients. In 3 patients, a small distal dissection was successfully stented, and in 1 case embolization of debris occurred down the distal vessel, resulting in a small procedural myocardial infarction. Only 1 patient out of 93 (1%) developed a large distal dissection requiring the deployment of multiple stents, compared with 22 of the remaining 374 patients (5.9%) who underwent conventional angioplasty. This was a significant difference in favor of direct stenting (Chi-square, p < 0.05). When compared with a cohort of patients matched by lesion grade treated with conventional stenting, direct stenting used significantly less contrast per case (154 +/- 7.6 ml compared with 202 +/- 9.5 ml for conventional stenting; p = 0.0001). CONCLUSION: Direct stenting is a safe and effective method for treating coronary artery disease. In appropriately selected cases, it has a low rate of procedural failure and results in less contrast usage and fewer distal complications than conventional angioplasty and stenting.

Angioplasty, Balloon, Coronary↗
PubMed2000

A study of communication in the Cardiac Surgery Intensive Care Unit and its implications for automated briefing.

We present a study of the information transferred among caregivers in the context of cardiac surgery and use the study to evaluate a system, MAGIC, that we are developing for automated generation of briefings. Our framework integrates cognitive and quantitative evaluation methods and features three standards that reflect current practice in the Cardiothoracic Intensive Care Unit (CTICU). Using experimental design to compare human-generated and machine-generated briefings, we show that MAGIC's current level of performance is useful. Moreover, MAGIC could help improve information flow in the CTICU by providing a consistent set of information earlier than in current practice. The separate standards are also consistent in suggesting specific modifications that may be necessary for iterative design and further system development.

Communication↗
PubMed2000

Additive antiviral effects of lamivudine and alpha-interferon in chronic hepatitis B infection.

alpha-Interferon has limited efficacy against chronic hepatitis B virus (HBV) infection. Nucleoside analogues may confer greater benefits, however, it is likely that combination therapies will be required for effective control of this infection. We investigated the antiviral effect of lamivudine and interferon therapy in eight patients with high HBV-DNA levels. Six patients received lamivudine/interferon combination therapy followed, after a 6-month drug-free period, with lamivudine monotherapy. Mean HBV viral load (copies/ml) reduction was significantly greater after 4 months of combination therapy (4.3 x 10(3)) compared to an equivalent period of lamivudine monotherapy (2.9 x 10(2)) (P=0.03). Two patients were given 6 months of lamivudine/interferon combination therapy followed immediately by lamivudine monotherapy. Cessation of interferon in these patients led to a rapid 1-2 log10 increase in HBV viral load. These findings suggest that alpha-interferon has a direct antiviral effect on chronic HBV infection, which may be additive to, or synergistic with lamivudine.

Antiviral Agents↗
PubMed2000

Six sigma.

Explore the source record for details and available documents.

Cost Savings↗
PubMed2000

Hospital managers of the future--what are their needs?

In the course of conducting a review of the international Hospital Management MA course at the Nuffield Institute for Health, Leeds University, the reviewers conducted a survey of international health care trends, especially in developing countries, and considered their implications for hospital and health managers. The demands on managers are becoming more complex and require new expertise in working autonomously, financial planning, organisation development, risk management in physical resource use, and quality of clinical care. The course has been restructured to take account of the identified needs. This article discusses the development needs of hospital managers in the context of changing international health trends, and how they can be met. It arises from a review of the Hospital Management course at Leeds University, which has been restructured to enable managers to meet these challenges. The account may interest not only health management development practitioners, but also hospital managers worldwide who reflect on their working environment, and how to respond to it.

Delivery of Health Care↗
PubMed1999

8-aminoquinolines as anticoccidials - Part III.

Analogues of the antimalarial pentaquine, 1, in which the nature of the side-chain on the 8-amino position was varied, were prepared and evaluated for anticoccidial activity both in vitro and in vivo. Specifically, both the inter-nitrogen distance and the nature of the terminal amino group were investigated. Novel analogues of equal or improved efficacy in vitro and in vivo to pentaquine were discovered.

Aminoquinolines↗