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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 19 recordsLinked to original sources
PubMed2006

A preliminary risk assessment of organochlorines accumulated in fish to the Indo-Pacific humpback dolphin (Sousa chinensis) in the Northwestern waters of Hong Kong.

The Indo-Pacific humpback dolphin is considered threatened due to several factors including pollution in Hong Kong and the risks due to consumption of fish tainted with polychlorinated biphenyls (PCBs) and organochlorine pesticides were assessed. Six species of fish Collichthys lucida, Pseudosciaena crocea, Johnius sp., Thryssa sp., Mugil sp. and Trichiurus sp., which comprise the main prey species of humpback dolphins were collected for analyses. Risks due to total PCBs, total TEQs, PCB 118 and the pesticides were assessed with the use of toxicity reference values as the threshold reference benchmarks. The calculated risk quotients (RQs) showed that the risks associated with organochlorines were generally low. The highest RQ was associated with total TEQs suggesting that dioxin-like PCBs may pose the highest risk to the dolphins. The HCHs, total PCBs and heptachlor had comparatively high RQs and thus they should also be the priority organochlorines that would require further investigation.

Animals↗
PubMed2006

Determination of the bioavailability of [14C]-hexaminolevulinate using accelerator mass spectrometry after intravesical administration to human volunteers.

Hexaminolevulinate (HAL) is a diagnostic agent that allows the visualization of tumor tissue in the bladder by fluorescence cystoscopy. It is administered intravesically via a catheter for 1 hour, followed by blue light bladder inspection to induce selective red tumor fluorescence. Hexaminolevulinate should ideally be confined to the bladder only, but it is likely that some absorption occurs during administration, and therefore the systemic bioavailability is of interest. The bioavailability of HAL was determined by intravesical and intravenous administration of [14C]-HAL hydrochloride to 8 human volunteers. To reduce the radiation dose as low as possible, the ultrasensitive analytical technique of accelerator mass spectrometry was used to measure [14C]-HAL. The bioavailability of [14C]-HAL after intravesical and intravenous administration was determined from the respective area under the curve based on total radioactivity and was determined to be 7% (range, 5%-10%; 90% confidence interval). The systemic absorption of [14C]-HAL after intravesical administration is low and supports previous clinical experience with HAL showing no systemic side effects.

Administration, Intravesical↗
PubMed2005

Pollution monitoring in Southeast Asia using biomarkers in the mytilid mussel Perna viridis (Mytilidae: Bivalvia).

Mytilid mussels have been extensively used in marine pollution monitoring programmes in temperate regions of the world although widespread subtropical representatives such as Perna viridis have only comparatively recently been utilised to monitor the sublethal effects of pollution in Southeast Asia. P. viridis is considered a subtropical equivalent of the temperate Mytilus sp. and has considerable potential for pollution monitoring throughout its geographical range. This paper reviews the current status of biomarkers in P. viridis and provides some recommendations on biological-effects monitoring to facilitate the assessment of coastal pollution in Southeast Asia.

Animals↗
PubMed2004

Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat reduces FMD for several hours, but there is inconsistent evidence about whether foods containing unsaturated fats impair FMD acutely. Little is known about the acute effects of omega-3 fatty acids on vascular reactivity. METHODS: We measured FMD before and 4 h after 3 test meals (50 g fat, 2,615 kJ) in 18 healthy adults with type 2 diabetes. The monounsaturated fatty acids (MUFA) meal contained 50 g fat from high oleic safflower and canola oils. Two additional meals were prepared by replacing 7% to 8% of MUFA with docosahexaenoic acid and eicosapentaenoic acid from sardine oil or alpha-linolenic acid from canola oil. RESULTS: In the sample as a whole, FMD was increased 17% at 4 h vs. the fasting baseline. After the MUFA meal, subjects with the largest increases in triacylglycerols had the largest FMD decreases. The opposite pattern was observed after meals containing docosahexaenoic acid and eicosapentaenoic acid or alpha-linolenic acid. In subjects with high fasting triacylglycerols, meals containing 3 to 5 g of omega-3 fatty acids increased FMD by 50% to 80% and MUFA alone had no significant effects on FMD. CONCLUSIONS/INTERPRETATION: Endothelium-dependent vasodilation was not impaired 4 h after meals containing predominantly unsaturated fatty acids. The fatty acid composition of the meal and the metabolic status of the individual determine the vascular effects of a high-fat meal.

Blood Flow Velocity↗
PubMed2004

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers.

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID trade mark ), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected. This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer.

Adolescent↗
PubMed2004

A preliminary risk assessment of trace elements accumulated in fish to the Indo-Pacific Humpback dolphin (Sousa chinensis) in the northwestern waters of Hong Kong.

In order to assess the potential risks associated with consumption of contaminated prey items to the Indo-Pacific Humpback dolphin (Sousa chinensis), fish species (Collichthys lucida, Pseudosciaena crocea, Johnius sp., Thryssa sp., Mugil sp. and Trichiurus sp.) representing the main food items of the dolphin were collected from the northwestern waters of Hong Kong, including the Sha Chau and Lung Kwu Chau Marine Park, which form the main habitat of the dolphin in Hong Kong. Within these waters, there are several potential sources of pollution including significant inputs from the Pearl River catchment, several major sewage outfalls and a series of mud pits that receive contaminated dredged sediments. Concentrations of thirteen trace elements (Ag, As, Cd, Co, Cr, Cs, Cu, Hg, Mn, Ni, Se, V, and Zn) in the fish tissue were analyzed by inductively coupled plasma mass spectrometer (ICP-MS). An assessment of the risks of adverse effects on the dolphin due to consumption of tainted fish was undertaken using two toxic reference benchmarks, namely the reference dose (RfD) and toxicity reference value (TRV). The risk quotient (RQ) calculated for each element showed that the risks from consumption of fish were generally low and within safe limits. The risks associated with arsenic, cadmium and mercury were, however, elevated. The highest calculated RQ was associated with total arsenic; however, the majority of arsenic in marine organisms tends to be in the non-toxic organic form, and the actual risk to the dolphin due to this metalloid is likely to be lower.

Animals↗
PubMed2003

Lysosomal membrane stability, phagocytosis and tolerance to emersion in the mussel Perna viridis (Bivalvia: Mytilidae) following exposure to acute, sublethal, copper.

The mytilid mussel Perna viridis is distributed throughout the Indo-Pacific region and is potentially a suitable candidate for biological effects (biomarker) monitoring in the subtropics. A suite of cytological and physiological responses to acute (48-72 h) copper exposures of 50-200 microgl(-1) were assessed in order to determine the suitability of P. viridis for marine pollution monitoring. Copper elicited significant destabilisation of the haemocyte lysosomal membranes and also impaired phagocytosis. Survival during emersion following exposure to copper was not related to the experimental copper exposures suggesting that higher metal concentrations may be required to interfere with anaerobic enzymes responsible for suppression of metabolism. Based on this preliminary study, cytological biomarkers evaluated in the haemocytes extracted from P. viridis should prove an effective non-destructive means of assessing metal pollution throughout the mussels subtropical range.

Animals↗
PubMed2003

Promoting better use of the PSA test in general practice: randomized controlled trial of educational strategies based on outreach visits and mailout.

BACKGROUND: Prostate-specific antigen (PSA) testing for prostate cancer is controversial. Demand for PSA testing is likely to rise in the UK, Australia and other western countries. Primary care needs to develop appropriate strategies to respond to this demand. OBJECTIVES: Our aim was to compare the effectiveness of educational outreach visits (EOVs) and mailout strategies targeting PSA testing in Australian primary care. METHODS: A randomized controlled trial was conducted in general practices in southern Adelaide. The main outcome measures at baseline, 6 months and 12 months post-intervention were PSA testing rates and GP knowledge in key areas relating to prostate cancer and PSA testing. RESULTS: The interventions were able to demonstrate a change in clinical practice. In the 6 months post-intervention, median PSA testing rate in the EOV group was significantly lower than in the postal group, which in turn was significantly lower than the control group (P < 0.001). Statistically significant differences were not, however, maintained in the 6-12 month post-intervention period. The EOV group, at 6 months follow-up, had a significantly greater proportion of "correct" responses than the control group to questions about prostate cancer treatment effectiveness (P = 0.004) and endorsement of PSA screening by professional bodies (P = 0.041). CONCLUSIONS: Primary care has a central role in PSA testing for prostate cancer. Clinical practice in this area is receptive to evidence-based interventions.

Adult↗
PubMed2003

A randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 in the treatment of metastatic malignant melanoma.

We conducted a randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 (IL-2) as treatment for stage IV malignant melanoma. The objectives were to establish the safety and efficacy of SRL172 with and without IL-2. All patients had measurable metastatic disease and none received concurrent chemotherapy, radiotherapy, corticosteroids or any other investigational agent. Sixteen patients were randomized into each arm of the trial prior to closure. The trial was halted prematurely when no responses were seen in the first 16 patients receiving SRL172 alone, predicting a response rate of less than 20%. Three partial remissions were seen in the 16 patients receiving SRL172 + IL-2. These patients remained on monthly SRL172 + IL-2, with disease progression at 12, 15 and 23 months. They continued on the trial regimen following surgical management of their disease progression. This trial provides preliminary evidence of a new, non-toxic, immunotherapeutic regimen in the management of malignant melanoma. Further trials are required to establish a definitive response rate and to compare the combination regimen with the regimen of low-dose IL-2 used in this trial. A biological basis for the responses seen in the SRL172 + IL-2 arm also needs to be established.

Adjuvants, Immunologic↗
PubMed2002

Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer.

OBJECTIVE: To establish the safety and toxicity of an allogeneic human tumour cell vaccine in patients with hormone-refractory prostate cancer, and to determine any biochemical, immunological or clinical response to vaccination. PATIENTS AND METHODS: Sixty patients with hormone-refractory prostate cancer were recruited and randomly allocated into four equal groups. Three cell lines (from a bank of four) were administered initially every 2 weeks and then monthly, in conjunction with the immunostimulant Mycobacterium vaccae (SRL-172), each group receiving a different combination of the four cell lines. The patients' serum prostate-specific antigen (PSA) levels were monitored regularly, and the immune response to the vaccine measured using nonspecific intracellular cytokines and specific humoral and cell-mediated assays. RESULTS: The vaccine was safe and well tolerated with no major side-effects. Whilst several patients had a decline in PSA from the entry level, there was no significant decrease that could be attributed solely to the vaccine. However, the immunological data were more encouraging, with several patients from each arm of the trial having an increase in cytokine production, increases in specific antibodies and evidence of T-cell proliferation in response to the vaccinations. CONCLUSION: The failure of the vaccine to produce a PSA response in the patients in the trial is not surprising considering the stage of the disease. The high PSA levels on entry indicate that the burden of disease was probably high and thus this was an extremely challenging group of patients in which to try and elicit a response through immunotherapy. However, the immunological evidence of a response to the vaccine was encouraging and suggests that further exploration of immunotherapy in less advanced disease may yield more encouraging clinical responses.

Aged↗
PubMed2001

Ecocytological and toxicological responses to copper in Perna viridis (L.) (Bivalvia: Mytilidae) haemocyte lysosomal membranes.

Bivalve lysosomes are sites of intense intracellular digestion. Lysosomes accumulate many pollutants to high concentrations resulting in membrane destabilisation. Consequently, the elucidation of lysosomal membrane integrity utilising the neutral red assay has been used to good effect in pollution monitoring. Naturally occurring environmental stressors also have the potential to destabilise the membrane. Exposure to elevated copper concentrations and extremes of temperature, salinity, hypoxia, emersion and inadequate ration were investigated in haemocyte lysosomes from the tropical bivalve, Perna viridis. Elevated copper concentrations destabilised the membrane although responses were not entirely related to the exposure-concentration. Environmental stressors induced through higher thermal regimes (29 degrees C and 35 degrees C), hyposalinity (10-25/1000) and prolonged emersion elicited significant lysosomal membrane destabilisation. Hypoxia and inadequate ration did not significantly effect membrane stability. The haemocyte lysosomal membranes were generally resistant to exogenous alterations within normal ranges and only showed significant labilisation at environmental extremes. P. viridis haemocyte lysosomal membrane biomarkers should, therefore, prove robust to natural stressors when deployed in marine monitoring programmes and thus prove a valuable, rapid, cost-effective cytological marker of pollution.

Animals↗
PubMed2001

The incentive effects of the Medicare indirect medical education policy.

Medicare provided teaching hospitals with US$ 5.9 billion in supplemental graduate medical education (GME) payments in 1998. These payments distort input and output prices and provide teaching hospitals with incentives to hire residents, close beds, and admit more Medicare patients. The structure of the GME payment policy creates substantial variation in input and output prices between teaching hospitals. We examine the extent to which hospitals responded to these financial incentives using a panel data set of 3,900 hospitals, including over 900 teaching hospitals. We find that teaching hospitals did hire residents and close beds in response to the Medicare policy, but did not increase Medicare admissions or alter their use of registered nurses (RNs).

Aged↗
PubMed2001

Designing a community-based fourth-year obstetrics and gynaecology module: an example of innovative curriculum development.

INTRODUCTION: This paper describes the design and evaluation of the community-based obstetrics and gynaecology module at St Bartholomew's and the Royal London School of Medicine and Dentistry. This module sets out to comply with the General Medical Council's recommendations of encouraging students to consider the community perspective, and places less emphasis on a disease-orientated approach. OBJECTIVES: The development of the module, issues of improving student acceptance of the course, staff development and the benefits of community teaching in obstetrics and gynaecology are discussed. MODULE ORGANIZATION: The 2-week module precedes the 8-week hospital obstetrics and gynaecology firms that occur in the fourth undergraduate year. The course is organized into three components: general practice, departmental teaching, and self-directed learning. Students are allocated to general practices for their clinical teaching, for eight sessions. Seven departmental sessions are run by the Academic Department of General Practice and Primary Care. These include a review of the students' self-directed learning. EVALUATION AND CONCLUSION: Evaluation data are reported for the three components of the course. Overall the majority of students rated the module as useful, GP attachments being most favourably received. The majority of students have grasped the basic obstetric and gynaecological history and examination skills and found this useful before starting their hospital firms. Aspects of a specialist subject, such as, obstetrics and gynaecology, can be taught successfully in the community and GP tutors are, as yet, an untapped source of excellent obstetric and gynaecology teaching.

Community Medicine↗
PubMed2001

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.

OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.

Adolescent↗
PubMed2001

Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction.

Hemorrhagic shock (HS), secondary to major blood loss, frequently precedes multiple organ dysfunction and is accompanied by a surge in circulating catecholamine levels. Expression of the cardiodepressant cytokine, tumor necrosis factor-alpha (TNF-alpha), has been observed in the heart after HS and resuscitation (HS/R) and alpha(1)-adrenergic blockade prevented translocation of the nuclear transcription factor, NF-kappa B, to the nucleus. We hypothesized that alpha(1)-adrenergic stimulation induces myocardial TNF-alpha expression, which results in depressed cardiac function after HS/R. The role of alpha(1)-adrenergic stimulation in myocardial TNF-alpha expression and depressed cardiac function after HS/R was assessed by treatment with the alpha(1)-adrenergic inhibitor, prazosin hydrochloride (1 mg/kg ip), for 1 h before the onset of hemorrhage. In addition, TNF-alpha was neutralized with a specific antibody (600 microl/kg iv) 5 min before hemorrhage. HS was induced by the withdrawal of blood to a mean blood pressure of 50 mmHg for 1 h. Contractile function was measured with the use of a Langendorff apparatus 2 h after the end of HS. HS/R led to significant decreases in left ventricular developed tension and in the maximal rate of pressure increase over time during both contraction and relaxation. Myocardial expression of TNF-alpha measured by enzyme-linked immunosorbent assay increased significantly after 30 min of hemorrhage and peaked after 60 min of HS and 45 min of resuscitation. Depression in cardiac function after HS/R was reversed by 85% in hearts from rats treated with a TNF-alpha neutralizing antibody and by 90% in hearts from rats treated with prazosin hydrochloride. We conclude that HS activates a alpha(1)-adrenergic pathway, resulting in TNF-alpha expression in the heart and depressed myocardial contractile function.

Adrenergic alpha-Agonists↗