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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

At least 19 recordsLinked to original sources
PubMed2006

Morphological and molecular characteristics of a species of Hepatozoon Miller, 1908 (Apicomplexa: Adeleorina) from the blood of Isoodon obesulus (Marsupialia: Peramelidae) in Western Australia.

Examination of blood films as part of a study to assess the health status of the southern brown bandicoot Isoodon obesulus (Shaw) in Western Australia revealed the gamonts of a haemogregarine parasite in some samples, the first to be recognised in a bandicoot in this state. Light microscope morphological characteristics and partial sequence of the 18S rRNA gene were used to describe these organisms. Morphological characters did not differentiate the organism in the current study from previously reported Hepatozoon peramelis (Welsh & Dalyell, 1909). Phylogenetic analysis has not previously been reported for any species of Hepatozoon from Australian marsupials and consequently could not be used to confirm the identity of the organism in the current study as that described in the 1900s. If this organism is H. peramelis, then it has a wide distribution, being found in three species of bandicoot, in western and eastern Australia and the in island state of Tasmania.

Animals↗
PubMed2006

PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells.

Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance to chemotherapy. RCC cells overexpress the transcription factor, PAX2, normally expressed in fetal kidney but downregulated at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned that PAX2 may confer resistance to cisplatin-induced apoptosis in RCC. Here, we show that PAX2 confers resistance to cisplatin-induced apoptosis in normal kidney cells and fetal kidney explants. Human embryonic kidney 293 cells transfected with a PAX2 expression vector and exposed to cisplatin (40 microM) exhibited 45 +/- 15% as much caspase-3 cleavage compared to control cells. Conversely, murine collecting duct cells stably transfected with PAX2 antisense cDNA had twofold increase in cisplatin-induced apoptosis. Murine fetal (embryonic day 15) kidney explants from PAX2(1Neu)+/- mice exposed to cisplatin (25 microM x 24 h) had 50% increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining). We then show that RCC cells (CAKI-1 (human, Caucasian, kidney, carcinoma) and ACHN (human, Caucasian, kidney, adenocarcinoma)) express PAX2 protein. PAX2-small interfering RNA (100 nM) reduces endogenous PAX2 protein (10% of baseline) and induces apoptosis (Annexin-V staining). Pax2 knockdown sensitized RCC cells to cisplatin-induced apoptosis, killing 50-60% of cisplatin-resistant ACHN and CAKI-1 cells. These findings suggest that PAX2 confers resistance to cisplatin-induced apoptosis in non-transformed kidney cells and fetal kidney explants. Similarly, Pax2 overexpression in RCC cells contributes to cisplatin resistance. Conceivably, a therapeutic strategy that inactivates Pax2 in vivo might enhance the efficacy of conventional cytotoxic drugs against RCC.

Adenocarcinoma↗
PubMed2006

Thrombophilia in pregnancy: a systematic review.

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Female↗
PubMed2006

Familial factors in diabetic nephropathy: an offspring study.

AIMS: Familial clustering of diabetic nephropathy in patients with Type 2 diabetes suggests that inherited factors predispose to diabetic nephropathy, but the nature of these factors is uncertain. The aim of the study was to compare the prevalence of known risk factors for nephropathy in non-diabetic offspring of Type 2 diabetic patients with and without nephropathy and in control subjects. METHODS: Three groups of patients were recruited with 40 or 41 subjects in each group. These were subjects having one Type 2 diabetic parent with nephropathy (DN); subjects having one parent with Type 2 diabetes without nephropathy (DnoN), and non-diabetic unrelated control subjects with no personal or parental history of diabetes (Control subjects). RESULTS: The median (interquartile range) albumin/creatinine ratio (ACR) was 1.40 (0.96-2.90) mg/mmol in DN; 0.94 (0.50-1.46) mg/mmol in DnoN and 1.22 (0.66-1.83) mg/mmol in Controls (ANOVA: P = 0.03). ACR was higher in group DN than in DnoN (P < 0.006) and in Control subjects (P < 0.03), but there was no difference between DnoN and Control subjects. Twenty-four-hour ambulatory blood pressure monitoring showed mean daytime systolic blood pressure to be significantly higher in group DN than in DnoN (P < 0.02) or Control subjects (P < 0.01) (ANOVA: P = 0.004). Fasting insulin, HOMA-IR, interleukin-6 (IL-6) and C-reactive protein (CRP) were similar in the three groups. CONCLUSION: Our data provide further evidence that genetic factors are important in determining urinary albumin excretion and renal disease associated with Type 2 diabetes and suggest that genes that affect systemic arterial blood pressure but not those relating to insulin resistance or inflammation are likely to be implicated.

Adult↗
PubMed2006

Effects of temperature and duration of sample storage on the haematological characteristics of western grey kangaroos (Macropus fuliginosus).

OBJECTIVE: To investigate the effects of storage duration and temperature on haematological analyses performed on blood from the western grey kangaroo (Macropus fuliginosis). METHOD: Blood samples from five western grey kangaroos were stored at 4 degrees C, 24 degrees C and 36 degrees C. Each sample was analysed haematologically over a 5-day period. RESULTS: The blood samples maintained optimal stability at 4 degrees C. At this temperature the haematological values remained essentially unchanged for the duration of the study, while samples stored at 36 degrees C and 24 degrees C showed significant changes in some haematological measures by 12 h and 48 h, respectively. Disturbances in leukocyte morphology were evident, to varying degrees, in all samples. CONCLUSIONS: Blood samples from macropodids should be tested within 48 h of collection if stored at a room temperature of about 24 degrees C. Where testing is to be delayed for more than 48 h, samples should be refrigerated as soon as possible. Exposure of samples to heat in excess of 24 degrees C should be avoided at all times.

Animals↗
PubMed2006

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

OBJECTIVES: To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003. REVIEW METHODS: In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group. RESULTS: In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective (ICER pound6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER pound202,402). Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated. CONCLUSIONS: Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Cost-Benefit Analysis↗
PubMed2005

Does aerobic fitness influence microvascular function in healthy adults at risk of developing Type 2 diabetes?

AIM: To investigate whether aerobic fitness is associated with skin microvascular function in healthy adults with an increased risk of developing Type 2 diabetes. METHODS: Twenty-seven healthy normal glucose-tolerant humans with either a previous diagnosis of gestational diabetes or having two parents with Type 2 diabetes and 27 healthy adults who had no history of diabetes were recruited. Maximal oxygen uptake was assessed using an incremental exercise test to exhaustion. Skin microvascular function was assessed using laser Doppler techniques as the maximum skin hyperaemic response to a thermal stimulus (maximum hyperaemia) and the forearm skin blood flow response to the iontophoretic application of acetylcholine (ACh) and sodium nitroprusside. RESULTS: Maximal oxygen uptake was not significantly different in the 'at-risk' group compared with healthy controls. Maximum hyperaemia was reduced in those 'at risk' (1.29 +/- 0.30 vs. 1.46 +/- 0.33 V, P = 0.047); however, the peak response to acetylcholine or sodium nitroprusside did not differ in the two groups. A significant positive correlation was demonstrated between maximal oxygen uptake and maximum hyperaemia (r = 0.52, P = 0.006 l/min and r = 0.60, P = 0.001 ml/kg/min) and peak ACh response (r = 0.40, P = 0.04 l/min and r = 0.47, P = 0.013 ml/kg/min) in the 'at-risk' group when expressed in absolute (l/min) or body mass-related (ml/kg/min) terms. No significant correlations were found in the control group. CONCLUSIONS: In this 'at-risk' group with skin microvascular dysfunction maximal oxygen uptake was not reduced compared with healthy controls. However, in the 'at-risk' group alone, individuals with higher levels of aerobic fitness also had better microvascular and endothelial responsiveness.

Adult↗
PubMed2005

Pyruvate kinase deficiency in a Somali cat in Australia.

A 7-year-old neutered male Somali cat, bred in Western Australia, was presented for investigation of jaundice and severe anaemia. Splenomegaly and hepatomegaly were evident on physical examination. Severe anaemia, along with leukopenia and increased liver enzymes, were present on laboratory evaluation. Clinical investigation identified cholangitis and treatment for this resolved the jaundice but failed to resolve the anaemia. Treatment for Mycoplamsa haemofelis was administered concurrently. Genetic testing was then performed and pyruvate kinase deficiency was identified, the first time this has been reported in an Australian cat. Treatment with immunosuppressive medication was not successful.

Anemia, Hemolytic, Congenital↗
PubMed2005

Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus.

BACKGROUND: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. OBJECTIVE: To identify the best drug, dose, and treatment. PATIENTS AND METHODS: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. RESULTS: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). CONCLUSIONS: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.

Acute Disease↗
PubMed2004

Meningitis in a dog caused by Prevotella oralis.

Prevotella oralis, an obligate Gram-negative anaerobe, was shown to be the cause of meningitis in a two-year-old crossbreed dog. The dog had a six-week history of lethargy and neck pain. On presentation, the animal was reluctant to walk, had a stiff gait and neck pain on flexion. Analysis of cerebrospinal fluid documented a neutrophilic pleocytosis (7488 cells/microl) and the presence of occasional intracellular bacterial coccobacilli. The aetiological diagnosis was confirmed by routine aerobic and anaerobic culture, and identification of the isolates. This report also reviews the literature of the documented cases of bacterial meningitis in dogs.

Animals↗
PubMed2004

Ultrasonic sludge treatment for enhanced anaerobic digestion.

Ultrasound is the term used to describe sound energy at frequencies above 20 kHz. High-powered ultrasound can be applied to a waste stream via purpose-designed tools in order to induce cavitation. This effect results in the rupture of cellular material and reduction of particle size in the waste stream, making the cells more amenable to downstream processing. sonix is a new technology utilising high-powered, concentrated ultrasound for conditioning sludges prior to further treatment. This paper presents recent results from a number of demonstration and full-scale plants treating thickened waste activated sludge (TWAS) prior to anaerobic digestion, therefore enhancing the process. The present studies have proved that the use of ultrasound to enhance anaerobic digestion can be achieved at full scale and effectively result in the TWAS (typically difficult to digest) behaving, after sonication, as if it were a "primary" sludge. The technology presents benefits in terms of increased biogas production, better solids reduction, improved dewatering characteristics of the digested sludge mixture and relatively short payback periods of two years or less subject to the site conditions and practices applicable at that time.

Australia↗
PubMed2003

Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells.

We investigated the expression and activity of arginine transporters and endothelial nitric oxide synthase (eNOS) in human placental microvascular endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1, CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light chain dimers were indicated by a shift in molecular mass detected under nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine. The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic analysis supported a two-transporter model attributed to system y+L and system y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h, either as the basal production of nitric oxide (NO) or as the accumulation of intracellular cGMP was not detectable. We conclude that HPMEC transport cationic amino acids by systems y+ and y+L and that basal eNOS expression and activity in these cells is low.

Amino Acid Transport Systems, Basic↗