Search PubMed⌕ Search

Biomedical subjects

D Allen

Publications and source records attributed to D Allen.

At least 19 recordsLinked to original sources
PubMed2006

Arsenic release from iron rich mineral processing waste: Influence of pH and redox potential.

This paper presents the effect of pH and redox potential on the potential mobility of arsenic (As) from a contaminated mineral processing waste. The selected waste contained about 0.47 g kg(-1) of As and 66.2 g kg(-1) of iron (Fe). The characteristic of the waste was identified by acid digestion, X-ray diffraction and sequential extraction procedures. Less than 2% of the total As was acid extractable with the remaining 98% associated with Fe-oxyhydroxides and oxides. Batch leaching tests at different pH conditions showed a strong pH dependence on arsenic and iron leaching. Arsenic leaching followed a "V" shaped profiles with significant leaching in the acidic and alkaline pH region. Acid extractable phases dissolved at acidic pH, while desorption of arsenic due to increase in pH resulted in high arsenic concentration at alkaline pH. Under aerobic conditions and pH 7, As solubility was low, probably due to its precipitation on Fe-oxyhydroxides. Maximum As solubilization occurred at pH 11 (3.59 mg l(-1)). Similarity in the As and Fe leaching profiles suggested that the release of As was related to the dissolution of Fe in the low pH region. In general, redox potential did not play a significant role in arsenic or iron solubilization. It was thus concluded that for this solid waste, desorption was the predominant mechanism in arsenic leaching. A simple thermodynamic model based on arsenic and iron redox reactions was developed to identify the more sensitive redox couple.

Arsenicals↗
PubMed2006

The influence of premenopausal hormones on severity of climacteric symptoms and use of HRT.

OBJECTIVES: There is wide variation in the severity of climacteric symptoms and we hypothesized that this could be a reflection of premenopausal hormone levels. METHODS: As part of a long-term cohort study of endocrine risk factors for breast cancer, blood had been collected between 1986 and 1990 from 1882 premenopausal women aged >or=35 years. Questionnaires on menopausal symptom severity were sent to 1,843 surviving women in 2001, of whom 1,434 replied. Estradiol, progesterone and testosterone levels were measured by radioimmunoassay in 680 women who reported a natural menopause and completed the symptom severity section in full. RESULTS: Symptom severity fell with rising premenopausal estradiol levels and women with higher premenopausal testosterone levels had more severe vasomotor symptoms. Over 70% of women with above-median severity of symptoms had used hormone replacement therapy (HRT). Those with higher testosterone levels were less likely to take HRT. CONCLUSIONS: Premenopausal hormone levels may predict risk of severe menopausal symptoms, which in turn influences use of HRT. Paradoxically, a high testosterone level was associated with more vasomotor symptoms but reduced use of HRT. Those at greatest risk of climacteric symptoms may be at lower risk of breast cancer because of premenopausal reduced estrogen exposure.

Adult↗
PubMed2006

Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells.

In addition to gonadotropins, steroidogenesis and proliferation of granulosa cells during follicular development are controlled by a number of intraovarian factors including growth differentiation factor-9 (GDF-9), bone morphogenetic protein-4 (BMP-4), and IGF-I. The objective of this study was to determine the effect of GDF-9 and BMP-4 and their interaction with IGF-I and FSH on ovarian granulosa cell function in cattle. Granulosa cells from small (1-5 mm) and large (8-22 mm) follicles were collected from bovine ovaries and cultured for 48 h in medium containing 10% fetal calf serum and then treated with various hormones in serum-free medium for an additional 48 h. We evaluated the effects of GDF-9 (150-600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation. In FSH plus IGF-I-treated granulosa cells obtained from small follicles, 300 ng/ml GDF-9 reduced (P < 0.05) progesterone production by 15% and 600 ng/ml GDF-9 completely blocked (P < 0.01) the IGF-I-induced increase in progesterone production. In comparison, 300 and 600 ng/ml GDF-9 decreased (P < 0.05) estradiol production by 27% and 71% respectively, whereas 150 ng/ml GDF-9 was without effect (P > 0.10). Treatment with 600 ng/ml GDF-9 increased (P < 0.05) numbers (by 28%) of granulosa cells from small follicles. In the same cells treated with FSH but not IGF-I, co-treatment with 600 ng/ml GDF-9 decreased (P < 0.05) progesterone production (by 28%), increased (P < 0.05) cell numbers (by 60%), and had no effect (P > 0.10) on estradiol production. In FSH plus IGF-I-treated granulosa cells obtained from large follicles, GDF-9 caused a dose-dependent decrease (P<0.05) in IGF-I-induced progesterone (by 13-48%) and estradiol (by 20-51%) production. In contrast, GDF-9 increased basal and IGF-I-induced granulosa cell numbers by over 2-fold. Furthermore, treatment with BMP-4 also inhibited (P < 0.05) steroidogenesis by 27-42% but had no effect on cell numbers. To elucidate downstream signaling pathways, granulosa cells from small follicles were transfected with similar to mothers against decapentaplegics (Smad) binding element (CAGA)- or BMP response element (BRE)-promoter reporter constructs. Treatment with GDF-9 (but not BMP-4) activated the Smad3-induced CAGA promoter activity, whereas BMP-4 (but not GDF-9) activated the Smad1/5/8-induced BRE promoter activity. We have concluded that bovine granulosa cells are targets of both GDF-9 and BMP-4, and that oocyte-derived GDF-9 may simultaneously promote granulosa cell proliferation and prevent premature differentiation of the granulosa cells during growth of follicles, whereas theca-derived BMP-4 may also prevent premature follicular differentiation.

Animals↗
PubMed2005

Managing advanced-stage cervical cancer.

The current staging methods and the definition of advanced cervical cancer are discussed. The clinical International Federation of Gynaecology and Obstetrics (FIGO) staging system has been found to be inaccurate and this limits treatment planning. More accurate management could be based on surgicopathological features of the tumour. However, the latest imaging techniques have the potential to give us this information in a non-invasive way. To deliver optimal treatment in advanced cervical cancer, we need to optimize the way we categorize the prognostic groups. Accurately delineating the extent of the disease will potentially minimize treatment morbidity and improve survival. The techniques of chemoradiation are also discussed in detail.

Antineoplastic Agents↗
PubMed2005

Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation.

The role of vitronectin (Vn) in thrombosis is currently controversial; both inhibitory and supportive roles have been reported. To monitor directly the function of Vn in thrombotic events at the site of vascular injury, we studied Vn-deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital microscopy thrombosis models. In the mesenteric arteriole model, vessel injury was induced by ferric chloride. We observed unstable thrombi and a significantly greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and frequent vessel re-opening occurred. In the cremaster muscle arteriole model, vessel injury was induced by a nitrogen dye laser. We observed significantly fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of Vn-/- mice. To define further the role of Vn in thrombus growth, we studied platelet aggregation in vitro. Consistent with our in vivo data, the second wave of thrombin-induced aggregation of gel-filtered platelets was abolished at a low concentration of thrombin in Vn-/- platelets. Interestingly, adenosine diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn-/- platelet-rich plasma (PRP) and this effect was attenuated by adding purified plasma Vn. We also observed increased platelet aggregation induced by shear stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus stabilizer. However, in contrast to released platelet granule Vn which enhances platelet aggregation, plasma Vn inhibits platelet aggregation.

Adenosine Diphosphate↗
PubMed2005

Bronchiolitis obliterans organizing pneumonia in a patient with non-Hodgkin's lymphoma following R-CHOP and pegylated filgrastim.

Bronchiolitis obliterans organizing pneumonia (BOOP) presents with fever, dyspnoea, pleuritic chest pain and hypoxia. The diagnosis can be made from radiological appearances on chest radiograph and CT scan correlated with histological findings following biopsy. We present a 52-year-old gentleman undergoing treatment for high grade non-Hodgkin's lymphoma who developed respiratory symptoms during chemotherapy. BOOP was diagnosed and he responded well to oral prednisolone. The cause of BOOP is often not certain. However, in this case we suspect pegylated filgrastim or rituximab as possible agents.

Antibodies, Monoclonal↗
PubMed2005

Transvaginal contraception--avoid the bladder.

We report two cases of female contraceptive methods, resulting in urological presentation, with bladder foreign bodies. History, mode of diagnosis and surgical extraction technique differed in both patients. The first, where a thermometer was lost intravesically whilst measuring an internal temperature, presented immediately. A plain abdominal X-ray confirmed the position of the foreign body. Extraction was performed cystoscopically with the thermometer intact. A second patient, with recurrent urinary tract infections, was found to have an intrauterine contraceptive device (IUCD) in her bladder on ultrasound. Attempts to remove it endoscopically failed, and an, open procedure was required to free the IUCD from the bladder sidewall.

Adult↗
PubMed2005

Collaborative study to establish the first international standard for quantitation of anti-HPA-1a.

BACKGROUND AND OBJECTIVES: This report describes the production of a freeze-dried preparation of pooled human plasma, containing immunoglobulin G (IgG) antibodies against the human platelet antigen 1a (HPA-1a). The material, coded 03/152, is proposed as an International Standard containing 100 arbitrary units of anti-HPA-1a for use in quantitative assays to determine the anti-HPA-1a activity in clinical samples. MATERIALS AND METHODS: Plasma samples containing potent anti-HPA-1a were pooled and freeze dried in 1-ml ampoules. In addition, three individual plasma samples were selected which had varying levels of anti-HPA-1a activity. The anti-HPA-1a activity of these three samples was determined by using a variety of quantitative assays with the proposed standard as a reference. RESULTS: An international collaborative study, which was part of the 2004 ISBT Platelet Immunology Workshop, involved 39 laboratories in 24 countries and showed that the anti-HPA-1a activity in three test samples could be reliably determined by using the proposed standard. CONCLUSIONS: Laboratories can use this standard to measure the anti-HPA-1a activity in patient's samples. Further studies are required to determine the relationship between anti-HPA-1a activity and clinical outcome in patients with neonatal alloimmune thrombocytopenia (NAIT).

Antibodies, Monoclonal↗
PubMed2005

Report on the 12th International Society of Blood Transfusion platelet immunology workshop.

BACKGROUND AND OBJECTIVES: The aims of the 12th International Society of Blood Transfusion (ISBT) Platelet Immunology Workshop were to evaluate the proficiency of molecular human platelet antigen (HPA) genotyping and detection of platelet antibodies of unusual specificity or reactivity, to assess whether quantification of anti-HPA-1a is practicable, and to determine the variability of reagents and components used in the monoclonal antibody immobilization of platelet antigens assay (MAIPA). MATERIALS AND METHODS: Forty participants from 23 countries were sent 10 samples for DNA typing, five samples for antibody detection, a freeze-dried anti-HPA-1a standard, three samples for anti-HPA-1a quantification and a MAIPA method questionnaire. RESULTS: The detection and identification of HPA antibodies varied from 2.7 to 95% of participants. The number of HPA genotyping errors per sample ranged from 0 to 3.96% per HPA loci. The majority of laboratories were able to assign an arbitrary number of units/ml of anti-HPA-1a activity to the unknown samples. The MAIPA questionnaire indicated a wide variation among participants, both in method and in reagents used. CONCLUSIONS: The results obtained from this workshop highlighted deficiencies in testing regimes and identified a need for internationally available reference materials.

Antibodies, Monoclonal↗
PubMed2005

Misinterpretation of radioisotope imaging in pelvic kidneys.

We report the case of a gentleman referred with apparent worsening function in a hydronephrotic left-sided pelvic kidney. Imaging with Tc-99m-Mercaptoacetyltriglycine (MAG 3) in 1999, showed that the left kidney contributed 46% of renal function with no evidence of obstruction. Three years later, repeat scanning showed ectopic kidney function had decreased to 20% and with worsening pain, nephrectomy had been suggested. Review of the second MAG 3 scan revealed that only posterior images had been obtained. With pelvic kidneys, the pelvis forms a barrier between the radioactively labelled tracer and the gamma camera, thus, reducing the amount of radiation detected and underestimating function. A subsequent Dimercaptosuccinic acid scan (DMSA) was carried out with posterior and anterior images, the latter showing split renal function was identical to that seen on the initial scan. In patients with pelvic kidneys, anterior views must be obtained during radionuclide scanning if unnecessary nephrectomy is to be avoided.

False Positive Reactions↗
PubMed2004

Aciclovir or valaciclovir for Bell's palsy (idiopathic facial paralysis).

BACKGROUND: The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases. OBJECTIVES: To assess the efficacy of aciclovir or similar agents for treating Bell's palsy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched April 2003), MEDLINE (from January 1966 to April 2003), EMBASE (from January 1980 to April 2003) and LILACS (from January 1982 to April 2003). We also contacted authors of identified trials. SELECTION CRITERIA: Randomised or quasi-randomised trials of aciclovir or valaciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy. DATA COLLECTION AND ANALYSIS: We identified six randomised trials. MAIN RESULTS: Three studies met our inclusion criteria, including 246 patients. One study evaluated aciclovir with corticosteroid versus corticosteroid alone, another study evaluated aciclovir alone versus corticosteroid and a further study evaluated valaciclovir with corticosteroid versus corticosteroid alone or versus placebo alone. Incomplete recovery after one year: data were not available. An analysis was performed on data reported at the end of the study period in each trial. The results from one study four months after the start of treatment significantly favoured the treatment group, whilst the results of the study three months after the start of treatment significantly favoured the control group. The results from the second study at four months showed no statistically significant difference between the three groups. Adverse events: relevant data were not reported in any of the three trials. Complete facial paralysis six months after start of treatment: only one patient had complete paralysis upon entering one of the studies. This patient was assigned to the control group and the level of recovery attained was not reported. Motor synkinesis or crocodile tears one year after start of treatment: data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir plus corticosteroid group over corticosteroid alone, another demonstrated an inconclusive result with no difference between the aciclovir and corticosteroid. The third study did not comment upon these sequelae. REVIEWERS' CONCLUSIONS: More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the effect of aciclovir or valaciclovir on Bell's palsy.

Acyclovir↗
PubMed2004

Effect of insulin-like growth factors (IGF), FSH, and leptin on IGF-binding-protein mRNA expression in bovine granulosa and theca cells: quantitative detection by real-time PCR.

To determine if insulin-like growth factor (IGF)-1 and -2, FSH, or leptin alter IGF-binding protein (IGFBP)-2, -3, -4, and -5 mRNA levels in bovine granulosa and (or) theca cells, granulosa and theca cells were collected from bovine ovarian follicles, plated for 48 h in 10% FCS and then treated for 24 h in serum-free medium containing various hormone treatments arranged in three different experiments. Amounts of IGFBP-2, -3, -4, and -5 mRNA were quantitated using fluorescent quantitative real-time RT-PCR. Neither 100 ng/ml of IGF-1 nor IGF-2 had an effect (P > 0.10) on IGFBP-2, -3, -4, or -5 mRNA levels in small-follicle (1-5 mm; Experiment 1) granulosa cells. In large-follicle (>7.9 mm; Experiment 2) granulosa cells, 100 ng/ml of IGF-1 increased (P < 0.05) IGFBP-2 mRNA levels above controls and 3 ng/ml of IGF-1; 100 ng/ml of IGF-1 also decreased (P < 0.10) IGFBP-5 mRNA levels compared to 3 ng/ml of IGF-1 or FSH or 100 ng/ml leptin, while 100 ng/ml of IGF-2 had no effect (P > 0.10) on IGFBP-2, -3, -4, and -5 mRNA levels (Experiment 2). At the doses tested, leptin and FSH had no effect (P > 0.10) on IGFBP-2, -3, -4, and -5 mRNA levels in large-follicle granulosa cells. In theca cells, IGF-2 decreased (P < 0.05) IGFBP-2 mRNA levels, but had no effect on IGFBP-3 or -4 mRNA expression (Exp. 3); IGF-1 did not affect (P > 0.10) thecal IGFBP-2, -3 or -4 mRNA levels. In contrast, IGF-1 but not IGF-2 increased (P < 0.01) thecal IGFBP-5 mRNA levels. Ligand blotting revealed that both IGF-1 and -2 increased IGFBP-2 and -5 (protein) and had no effect on IGFBP-3 (protein), whereas IGF-1 (but not IGF-2) increased IGFBP-4 (protein), suggesting IGFBP-2, -4, and -5 are post-transcriptionally regulated. These results suggest that expression of IGFBP-2, -3, -4, and -5 mRNA by granulosa and theca cells are differentially regulated by IGF-1 and -2, therefore discretely modulating the amount of bio-available IGFs to these cells depending upon the specific hormonal milieu.

Animals↗
PubMed2004

Analysis of vascular endothelial growth factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma.

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (NYSKA et al. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma.

Administration, Oral↗
PubMed2003

Deaths associated with restraint use in health and social care in the UK. The results of a preliminary survey.

Many aspects of the management of acutely disturbed behaviour have only relatively recently come under systematic scrutiny. Perhaps regrettably one of the last amongst the range of strategies that may be employed to be subjected to rigorous examination has been physical restraint. Considerable debate has recently taken place around what represents good practice in this sensitive and controversial area but the continuing dearth of research in some aspects of this area of practice has meant that this discussion has arguably been over reliant on 'expert' opinion. Questions continue regarding some fundamental issues of restraint, including the relative risks involved in alternative approaches, and anxieties have been expressed about the potential for injuries and death to result from restraint. This article outlines the results of a survey that sought to explore the incidence of deaths associated with restraint in health and social care settings in the UK. The outcome of an initial analysis of the cases identified is then discussed, with reference to the literature on restraint-related deaths, in order to identify the implications for practice.

Adult↗
PubMed2002

Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production.

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.

Chemokines↗