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1
Gray, Atherton. "Immunoliposomes in haematology." Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/26559.
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The aim of this thesis was to use antibody-directed liposomes to enhance the targeting of 1. fluorescent compounds for the detection of cell surface antigens and 2. cytotoxic compounds for delivery to specific cell populations. This involved the selection and production of a suitable species of liposome-protein conjugate from among those described in the literature. The choice was a small unilamellar liposome conjugated either to antibody or protein A via a covalent linkage mediated by the heterobifunctional reagent SPDP. Anti-immunoglobulin antibody was a more universal ligand than either specific antibody or protein A. The conjugate was made fluorescent by the encapsulation of carboxyfluorescein (CF) in the liposome and the maximally fluorescent concentration was determined at 20 mM CF. The probe was stable on storage over many months and had low non-specific staining characteristics. Applied to lymphocytes it gave a signal enhancement in order of magnitude greater than the conventional fluorescent-antibody method as measured by flow cytometry. This permitted the demonstration of the interleukin-2 receptor on resting polyclonal T-lymphocytes hitherto undetectable by conventional fluorescence. This set the threshold of detectability at approximately 1000 antigen copies per cell.
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Mainwaring, Gary. "Aspects of fish haematology." Thesis, Swansea University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627994.
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Swart, Luhan. "HIV-associated Hodgkin lymphoma at Groote Schuur Hospital, Western Cape, South Africa." Master's thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/27282.
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Background: Human immunodeficiency virus (HIV) is associated with an increased risk of developing Hodgkin lymphoma (HL). South Africa (SA) has the highest HIV prevalence rate in the world. There is currently no 5-year overall survival (OS) outcome based data for HIV-associated HL from SA. Methods: A bone marrow database was compiled of all bone marrow biopsies (BMB) reported at National Health Laboratory Service (NHLS) Groote Schuur Hospital (GSH) between January 2005 and December 2012. Patients who had a BMB performed for staging of HL or where HL was diagnosed on the BMB were included for further analysis. Clinical and laboratory data was extracted from medical and laboratory records. Primary outcome measures included histological subtype, bone marrow infiltration (BMI) by HL, CD4 count, HIV-viral load (HIV-VL), tuberculosis (TB) data, treatment with chemotherapy and 5-year overall survival (OS). Results: The database included 6569 BMB and 219 patients of these had HL and were included for analysis. The median age at presentation (32 years) was similar in the HIV+ and HIV-populations. While males predominated in the HIV-group, females predominated in the HIV+ group (male:female ratio of 1.5:1 vs 0.7:1, respectively). The majority of patients (71%) were HIV negative (HIV-) and 29% were HIV positive (HIV+). The diagnosis of HL was made on BMB in 17% of cases. BMI was seen in 37%(82/219) overall, and was found in more HIV+ patients (61%; 39/64) than HIV-patients (28%; 43/155; p= 0.03). The histological subtype varied according to HIV status with nodular sclerosis classical Hodgkin lymphoma (NSCHL) being most frequent in the HIV-group and classical Hodgkin lymphoma (CHL)-unclassifiable the most frequent in the HIV+ group. HIV+ patients had a median CD4 count of 149 x106/L and 39% were anti-retroviral therapy (cART) naive at HL diagnosis. HIV+ patients had received anti-TB therapy more frequently than HIV-patients (72% vs 17%; p= 0.007). More HIV+ patients did not receive chemotherapy than HIV-patients (31% vs 3%; p= 0.001). The 5-year OS was 56%. HIV+ patients with BMI had a 5-year OS of 18%. BMI, HIV status, low CD4 count, histological subtype and TB therapy had a statistical significant impact on 5-year OS (p< 0.01). Conclusion: BMB provided the diagnosis of HL in 17% of cases, confirming its diagnostic utility in our setting. BMI by HL was more common in HIV+ patients and was associated with significantly worse survival. Our cohort showed similar survival outcomes to other countries in Africa, Asia and Central America with comparable socio-economic constraints to SA.
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Antel, Katherine. "Splenectomy for immune thrombocytopenia : our 11-year experience." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/14134.
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Splenectomy has been practiced for the treatment of ITP for the past few decades. Currently it is utilised when a patient is either dependent or resistant to steroid treatment and the platelet count remains less than 30×109/L. Recently new agents have been added to the armamentarium used to treat ITP, including immune-suppressants such as rituximab and the new thrombopoetin-receptor agonists. This has brought into question the role of surgery for the treatment of ITP, and the need to compare the response and complication rates of splenectomy to these newer agents. Historic studies done on splenectomy for the treatment of ITP have been performed in the setting of low HIV prevalence. There is a relative paucity of data on the response rate in HIV-associated thrombocytopenia to splenectomy and the durability of response to splenectomy is unclear in this patient population. We retrospectively analysed 73 consecutive patients who underwent splenectomy for ITP from 2001 to 2011. The primary objective was to determine the rate of complete response, this was defined as a platelet count greater than 100×109/L at one year post splenectomy. Results were compared between HIV positive and HIV negative patients. The secondary objectives were: to evaluate the intra-operative and post†operative complications and mortality in the HIV positive and HIV negative groups, and to investigate for associations between co-morbidities, pre-operative treatment and response to splenectomy.
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Van, Schalkwyk Willem Adendorff. "The diagnostic utility of bone marrow biopsies performed for the investigation of fever and/or cytopenias in HIV-infected adults at Groote Schuur Hospital." Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/2834.
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This is a retrospective review of the results of consecutive bone marrow biopsies performed at our institution over a three year period on HIV positive patients for the investigation of fever and cytopenias. Clinical data, haematological parameters, morphology of bone marrow biopsy, Ziehl-Neelsen staining and microbiological culture results were analyzed. The aim of the study was to determine the diagnostic yield of this investigation.
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Makgoka, Seretloane Japhtaline. "Effects of bFGF (Basic Fibroblast growth factor) on the Haematopoietic Sequelae that follow transplantation." Master's thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/25551.
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Recovery following bone marrow transplantation is associated with the reduction in the clonogenic potential of stroma-adherent CD34⁺ progenitors. The bone marrow stroma is also affected, resulting in poor support for the growth of stroma-adherent multipotent progenitors that form blastic colonies (CFU-bl). To determine the possible mechanisms of marrow damage in patients treated with peripheral blood stem cells (PBSCs) and bone marrow transplantation (BMT), we studied the effects of bFGF, a cytokine known to stimulate the survival and proliferation of fibroblasts, on the propagation of clonogenic progenitors and the marrow stroma. METHODS: In order to obtain the optimal bFGF concentrations to be used on patients' haematopoietic progenitors and bone marrow rnicroenvironment, haematologically normal individuals were studied in dose response studies. Control mononuclear cells from the Ficoll-Histopaque interface layer were divided into two aliquots: one to establish a stromal layer and to culture fibroblastic progenitors (CFU-Fs) in the presence of 0, 2 and 20 ng/ml bFGF with and without 20 ng/ml heparan sulphate (HS). The second aliquot was for the selection of the progenitor population. Stroma was quantitated by placing culture dishes on a grid containing 1mm squares and scoring the number of squares occupied by stromal layers as the percentage area covered. After 3 weeks of culture, a single cell suspension was prepared by incubation of stroma with 5% trypsin solution, and number of cells in the dishes enumerated with a particle counter. CFU-Fs were terminated on the 9th day of culture, stained with May-Grilnwald-Giemsa and scored using an inverted microscope. From the second aliquot, CD34⁺ cells were incubated with paramagnetic beads and target cells isolated with a magnet. Selected l x l 04/ml cells were cultured on prefom1ed controls' stroma that has been treated with 0, 2 and 20 ng/ml bFGF. Stroma-adhered cells were covered with 0.3% agar and cultured for 6 days. Aggregates of more than 20 cells were counted as CFU-bl. RESULTS: In normal individuals, the median surface area of the petri dish covered by stroma at 3 weeks of culture was 55% (range 30-65) and was significantly improved upon the addition of 2 ng/ml (median 70%; range 50-95 ; p= <0.05) and 20 ng/ml bFGF (median 80%; range 65-99; p= 0.004). Stromal cell numbers were 0.61 x 10⁶/2ml (range 0. 15-1.66), and they increased significantly with the addition of 2 and 20 ng/ml bFGF (p=0.03). The median colony forming unit-blasts (CFU-bl) scores were 121.8 x 10⁴/ml (range 43-271), and they expanded significantly with the addition of 20 ng/ml bFGF with and without heparan sulphate (p=0.03 and 0.01). It was then concluded that the 2 and 20 ng/ml bFGF with heparan sulphate be used on patients' cells in vitro. The median surface area covered by stromal layers in patients' samples at 3 weeks was 40% (range 0-55 vs. normal 50%), and it was in1proved significantly upon the addition of bFGF (median 78 vs. 50%; p= 0.001). Supplementation of stromal layers with bFGF accounted for a significant increase in patients stromal cell numbers (2.11 vs. normal 0.61 x 106/2ml; p< 0.05). Patients' CD34⁺ cells panned on normal stromal layers resulted in significantly fewer CFU-bl (median 40 vs. normal 90 x 10⁴/ml CFU-bl; p=0.009), but CFU-bl numbers were corrected following the addition of bFGF, matching the scores achieved by normal individuals (85 vs. normal 90 x l 04/ml). Normal CD34⁺ cells proliferated poorly on patients' stromal layers in the absence of bFGF (3 9 vs. normal 90 x 10⁴/ml), but colony numbers increased significantly upon addition of bFGF (91 vs. normal 90 x 10⁴/ml CFU-bl). Thirteen patients receiving peripheral blood stem cells (PBSCs) and nine patients undergoing bone marrow transplantation (BMT) were compared. These two stem cell sources were then compared to the normal population. Stromal layers in patients receiving PBSC grafts covered a greater surface area than the area covered in patients undergoing BMT (median 65 vs. 30%). They also had higher blastic colony than scores from BMT recipients (47 vs. 12 x 10⁴/ml CFU-bl; p= 0.2). Results can be summarized that bone marrow stroma from patients receiving mobilized progenitor cells proliferates better than those receiving bone marrow grafts. It can be concluded that poor stromal layer and CD34⁺ cell proliferation following peripheral blood stem cell transplantation can be corrected by addition of basic Fibroblastic Growth Factor.
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Seth, Yunus S. "Review and re-appraisal of patients treated with splenectomy for immune thrombocytopenic purpura at five years and beyond." Master's thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/2833.
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Includes bibliographical references.The risk of pneumococcal infection post splenectomy is life long so all patients undergoing splenectomy are given polyvalent (23-valent) unconjugated pneumococcal polysaccharide vaccine, preoperatively. The aim of this study was 1. to measure the success of splenectomy at a tertiary institution at 5 years and beyond. 2. To review the incidence of complications peri-operatively and long term. 3. Review the need for possible re-vaccination (as recommended in American and British guidelines and 4. perform a re-appraisal of patients found to be refractory to treatment.
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Goolam, Hoosen Taahira. "Identification and characterisation of micrornas involved in the pathogenesis of HIV–associated non-Hodgkin's lymphoma." Master's thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/24883.
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Background: Since its discovery about three decades ago, the Human Immunodeficiency Virus (HIV) has claimed over millions of lives globally. Although our understanding of the mode of transmission and action of this causative agent for the Acquired Immune Deficiency Syndrome (AIDS) has increased through research, and treatment regimens developed and improved, in certain parts of the world the pandemic continues to expand. Sub-Saharan Africa, which is the epicentre of this global health concern, accounts for approximately 66% of the total number of individuals affected, with South Africa enduring the heaviest burden. South Africa has the world's largest antiretroviral therapy (ART) programme and as such, HIV infected people are living longer, and consequently the incidence of HIV co-morbidities has increased dramatically. HIV/AIDS defining cancers are such co-morbidities with Non- Hodgkin's lymphomas (NHL) being the second most common HIV-associated cancer. Diffuse Large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) are the main subtypes and both present aggressively in HIV positive patients with rapid progression. The use of highly active antiretroviral therapy (HAART) has decreased the incidence of DLBCL in HIV positive patients, however the prevalence of these cancers still remain high in some settings. It has been suggested that the pathogenesis of these cancers in HIV infected individuals is complex and different to that in HIV uninfected individuals, with the possibility that the virus may have an oncogenic role. This has already been demonstrated in the case of the HIV/AIDSdefining cancer Kaposi Sarcoma. However, the same has not been unequivocally demonstrated in HIV-associated NHL. In light of this, the mechanisms through which viruses and viral components promote cellular transformation is an area of active research. One of these mechanisms manipulated by viruses is through the dysregulation of cellular microRNAs (miRNAs) which are small non-coding RNA molecules that are key regulators of gene expression. While they are essential for normal cellular functioning, their expression has been found to be deregulated in diseases including cancer. Several studies have described specific miRNA signatures for NHLs including for DLBCL and BL but none have been described for the HIV-association of these cancers. Aim: The aim of this project was to identify and characterise miRNAs involved in the pathogenesis of HIV-associated NHLs. This thesis reports on the changes in expression of miRNAs in B-cells exposed to an attenuated form (structurally intact but non-infectious) of HIV. Methods: We designed a custom miRNA microarray to identify deregulated miRNAs in the BL cell line Ramos that were exposed to HIV compared to microvesicle treated cells. It was initially planned to use both normal B-cells (L1439A) and BL cells for analysis but Ramos was selected due to technical reasons for this step. Thereafter we validated selected miRNAs by quantitative real-time PCR (qPCR) using single-tube TaqMan® Assays which was predominantly performed in the lymphoblastoid cell line L1439A, which is derived from a healthy donor. We then focused on further characterising the role of one miRNA in the development of HIV-associated NHL by using prediction programmes to predict its putative gene targets and then confirmed its target by using qPCR and western blot analyses. Results: Extensive and comprehensive analysis of the array data led to the identification of a large number of miRNAs which were differentially expressed, with 32 being selected for further studies. These 32 miRNAs include 16 upregulated and 16 downregulated miRNAs, and were selected because they displayed changes in expression by two or more folds. Thereafter, four miRNAs, namely miR-363-3p, miR-222-3p, miR-200c-3p and miR-575, were chosen for validation based on their reported involvement in cancer for validation. The results of two miRNAs (miR-575 (upregulated) (p<0.05) and miR-200c-3p (downregulated) (p<0.05)) were found to be consistent with the results obtained from the miRNA microarray whilst the other two were opposite to that result (both downregulated) (p<0.05). Using online tools as well as the published literature, several potential target genes of miR-575 were identified, namely DENND5A, CDK1, CSTA and ATAD5. One particular target, the BH3- like motif containing inducer of cell death (BLID), which is involved in apoptosis, has previously been confirmed as a gene target in non small cell lung cancer. Using qPCR, we found that BLID messenger RNA (mRNA) was downregulated in normal B-cells when exposed to HIV-1 AT-2. Unfortunately, the BLID protein could not be detected using western blot analysis despite several attempts at detecting varying concentrations of the protein and using two different positive control cell lines. Conclusion: The reverse correlation, between miR-575 and BLID mRNA expression in the same cell line and under the same treatment conditions, supports the notion that the downregulation of miR-575 may be physiologically relevant. However, this could not be further verified as the BLID protein could not be detected in the L1439A cells, even in the microvesicle treated control cells. Future studies should look at further characterisation of miR- 575 in the pathogenesis of HIV-associated NHLs by investigating other predicted gene targets of the miRNA. This will then be followed by loss and gain of function assays to confirm the miRNA:mRNA relationship. Furthermore, functional analyses, such as measure of apoptosis, expression of key regulators of the cell cycle, and other cellular events characteristic of cancer should be carried out to define the role of the miR-575 in the development of HIV-associated lymphoma.
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Wu, Erxi. "Expression and regulation of ADAMs in cells derived from a range of haematological malignancies." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312292.
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Strouboulis, Ioannis John. "Regulation of the complete human #beta#-globin gene locus in transgenic mice." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239790.
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Bruce, David. "Antithrombin : structural variants and thrombosis." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386084.
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Edgar, Paul Francis. "The structure and function of corticosteroid-binding globulin." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263526.
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Ramorola, Beatrice Relebogile. "HIV alters the expression of miRNA hsa-miR-200c-3p in B-cells, leading to enhanced migration of lymphoma cells." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29178.
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Background: The sub-Saharan African region is one that is affected most by the HIV/AIDS pandemic, with South Africa being the country with the highest number of infected individuals at 7.06 million. Infection with HIV is often associated with co-morbidities, including HIV-associated Non-Hodgkin’s Lymphomas (HIV-NHLs). Burkitt’s lymphoma (BL), a highly aggressive cancer, is one of the most common NHLs associated with HIV infection. Despite receiving highly active anti-retroviral therapy, the prognosis for this HIV-associated lymphoma remains poor and the incidence keeps on increasing in this group of patients. Recent studies have shown that microRNA (miRNA) dysregulation play essential roles in the pathogenesis of many cancers, including NHLs. While several human pathogenic viruses have been shown to deregulate cellular miRNAs, to date, no comprehensive studies have been carried out to determine whether HIV infection can lead to miRNA dysregulation in B-cells, which may contribute to the development of HIV-associated lymphomas.
Objective: This research project aimed to validate the differential expression of selected miRNAs which were identified as potentially important in a PCR array, and characterise their roles in Burkitt’s lymphoma cells exposed to an attenuated strain of HIV-1, compared to control cells.
Methods: Single-tube TaqMan miRNA assays were used to validate the previously observed differential expression of four selected miRNAs in Burkitt’s lymphoma cell lines (Ramos and BL41) exposed to HIV-1 compared to matched-microvesicle treated (control) cells. Following validation, the role of miRNA hsa-miR-200c-3p in the development of HIV-associated BL was investigated. This was done by using online bioinformatic prediction tools, as well as literature searches, to identify gene targets. Thereafter, the differential expression of a selected gene target was investigated by qPCR and western blotting. The functional significance of the observed changes in miRNA and gene expression was investigated by performing cell viability and migration assays.
Results: Three upregulated (hsa-miR-575, hsa-miR-363-3p and hsa-miR-222-3p) and one downregulated (hsa-miR-200c-3p) miRNAs that were significantly deregulated by 2-fold or more (p< 0.05) in the PCR array were selected for validation. Thereafter, the miRNA hsa-miR200c-3p was selected for further analysis. Upon exposure to attenuated HIV-1, hsa-miR-200c3p was downregulated in the BL cell line Ramos, and this was reproducible in a second BL cell line BL41. The transcription factors ZEB1 and ZEB2, which are involved in cancer cell migration, were identified as targets of hsa-miR-200c-3p. Contrary to what is expected, the mRNA expression of both genes was found to be significantly downregulated in Ramos and BL41 exposed to attenuated HIV-1. At the protein level, in the Ramos cells, ZEB1 and ZEB2 matched what was observed for the mRNA. In contrast, both ZEB1 and ZEB2 protein were upregulated in BL41 cells under the same treatment conditions. At the functional level, the migration of both cell lines was enhanced when exposed to attenuated HIV-1, compared to control cells.
Conclusions: The present study has demonstrated that HIV-1 has the ability to modulate cellular miRNA expression in Burkitt’s lymphoma cells. Of these miRNAs, hsa-miR-200c-3p is consistently downregulated when two BL cell lines were exposed to HIV. The ZEB transcription factors ZEB1 and ZEB2, which promote Epithelial-to-Mesenchymal Transition (EMT) through enhancing cellular migration, were investigated as hsa-miR-200c-3p targets. The mRNA levels of ZEB1 and ZEB2 were downregulated in both cell lines under the same experimental conditions. This is contrary to what is expected, since miRNAs lead to the attenuation of transcription or translation of their target genes and a downregulation of a miRNA should lead to an upregulation of its target. However, protein expression rather than mRNA expression has been described as a more accurate indication of target validation for miRNAs. The protein expression levels for ZEB1 and ZEB2 correlated with the mRNA expression results observed in the Ramos cells. In the BL41 cells, ZEB1 and ZEB2 protein levels were upregulated. Furthermore, in both cell lines, an increase in migratory ability was observed when cells were exposed to attenuated HIV-1. These results demonstrate that exposure to HIV enhances the cancer phenotype and that this is potentially due to changes in cellular miRNA expression brought about by the virus or viral components. Future studies should focus on gain-offunction and loss-of-function studies to determine whether the increase in cell migration is specifically due to a decrease in hsa-miR-200c-3p.
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Tremlett, Catherine H. "Molecular epidemiology of VanA resistant enterococci on a haematology ward." Thesis, University of Manchester, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499916.
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Paterson, Pamela J. "The diagnosis and treatment of invasive mould infections in haematology patients." Thesis, University of Aberdeen, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425016.
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Histological appearances of many moulds overlap and there is a need for a method to allow identification in tissue specimens. Two methods for extracting fungal DNA from wax tissue sections, based on the TaKaRa DEXPAT TM kit and QIAampÒ DNA Mini Kit, were optimised and compared. DNA was amplified by PCR using pan-fungal primers, and detected by Southern blot hybridisation with a probe specific for Aspergillus fumigatus and A. flavus. The TaKaRa DEXPAT TM kit based method, with additional steps using lyticase and ethanol precipitation, was superior and was used to test sequential wax tissue specimens from 56 patients with IFI. PCR products not hybridising with the probe were identified by sequencing. The species was confirmed in all tissue culture positive cases (23 A. fumigatus or A. flavus, one Chaetomium globosum and one Scedosporium apiospermum). Of culture negative cases, a diagnosis of A. fumigatus or A. flavus was established in 25 and emerging moulds in two (one probable Alternaria species and one unidentified). Overall, emerging moulds were identified in 4 cases (7%) with a trend toward a temporal increase in these infections. This method provides a valuable diagnostic tool for both patient management and future antifungal and epidemiological trials. Reasons for therapeutic failure in IFI are unclear. Amphoterican B susceptibility of isolates cultured from tissue biopsies from patients who had received a median of 12 days therapy, were tested using a method based on the NCCLS M38-A broth microdilution method. The difficulty in treating IFI does not appear to be due to susceptibility of the isolates, but may be due to poor penetration of antifungal agents into infected tissue.
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James, Rebecca. "A study of the neonatal haematology of children with Down syndrome." Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/4063/.
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This thesis describes the establishment and initial findings of the Children with Down Syndrome Study, a birth cohort of children with DS. The Children with Down Syndrome Study was set up in order to characterise the haematology of neonates with Down syndrome and specifically to test the hypothesis that that this differed in this population. The study was carried out with the support of the Down Syndrome Association and the Down Syndrome Medical Interest Group, and through consultation with clinicians and families. Following a pilot study in the Yorkshire region it was established in over 60 hospitals across the north of England. The Children with Down Syndrome Study is the largest birth cohort of children with Down syndrome established to date, and this is the largest reported analysis of the haematology of neonates with Down syndrome. The results confirm that neonates with Down syndrome have a distinct haematological profile. Means and ranges for haematological parameters throughout the neonatal period are provided. The effects of gestational age, birth weight, postnatal age and the venepuncture to processing interval on the neonatal full blood count were examined, and this is the first report of factors that influence the haematological parameters in neonates with Down syndrome. In order to analyse the blood cell morphology a new approach to morphology was developed and validated. Morphological review of samples from neonates with Down syndrome demonstrated that blasts were common. Comparison with automated findings showed that manual review of a film is indicated to look for evidence of transient myeloproliferative disorder. This is also the largest longitudinal study of haematological parameters of children with Down syndrome beyond the neonatal period. The results showed that parameters changed between birth and 1 year, with most being stable thereafter. However, it appears that children with Down syndrome continue to have a distinct morphological profile.
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Pattipeiluhu, Shelly M. "A study of parasitic fauna of the flounder (Platichthys flesus L.) in the Tyne estuary." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295512.
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Mahmoud, T. T. "The haemocytes and heart activity of Episyrphus balteatus DeG. (Syrphidae: Diptera) and their response to environmental factors." Thesis, University of Newcastle Upon Tyne, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370147.
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Boyd, Helen Kathryn. "Erythropoietin and other growth factors in the anaemia of chronic disorders." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241268.
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Hassounah, Fadwa. "A study of some haemoglobinopathies using molecular genetic and mass spectrometric analytical techniques." Thesis, University of Salford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360389.
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Yong, Kwee Lan. "The effects of myeloid growth factors on phagocyte-endothelium interactions." Thesis, University College London (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388120.
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Slupsky, Joseph R. "Mechanisms of monoclonal antibody-induced platelet activation." Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240868.
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Lwaleed, Bashir Abdulgader. "Urinary procoagulant activity in health and disease method development and clinical application." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390721.
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Atherton, Kirsten. "How do haematology patients make sense of clinical information? : a qualitative study." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2027839/.
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Haematological cancers are often unpredictable, leaving clinical decisions to be made throughout the trajectory of the illness. In this context, the way patients make sense of complex clinical information becomes particularly important. The study aimed to understand the ways in which patients make sense of clinical results, and to identify the psychological and other influences on this process. Semi-structured interviews were conducted with 20 patients who had been diagnosed with haematological cancer and had received results from clinical investigations or relating to treatment response. A constant comparative approach was taken for analysis. Patients described the need for information to be carefully managed, and the alarming nature of information that they did not experience as having been managed for them. Where patients had difficulty trusting their clinician they found it more difficult to accept and be content with the information the clinician provided. These findings can be illuminated using attachment theory. There are also clinical implications for how clinicians could give patients confidence in their ability to manage the uncertainty associated with haematological cancer. By facilitating an attachment process patients could be helped to feel that they are able to trust and build hope from the information they receive.
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Booth, Christopher. "Collaboration of Ezh2 and Runx1 inactivating mutations in malignant haematopoiesis." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:3f3b18b1-5875-42ed-b025-cf0dd457b99f.
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Extensive efforts have shed light on the identity and biology of cancer stem cells, required and sufficient for the propagation of hematological malignancies and solid tumours. Much less is understood about the closely related issue as to the identity and properties of the normal stem and progenitor cells targeted by oncogenic lesions, and how the nature of the targeted cell might impact on the biology and clinical picture of the resulting cancer. To address this, we developed a mouse model allowing targeted inactivation of Ezh2 and Runx1 to different haematopoietic compartments. Inactivating mutations of EZH2 and RUNX1 frequently co-occur in haematological malignancies with markedly different phenotypes including myelodysplastic syndrome (MDS) and early thymic progenitor (ETP) leukaemia. Inactivation of Ezh2 and Runx1 in adult haematopoietic stem cells (HSCs) resulted in perturbed haematopoiesis leading to development of an MDS-like disease. Unexpectedly, this MDS phenotype could be fully reproduced when Ezh2 and Runx1 inactivation was targeted to multipotent progenitors (MPPs) using Flt3-Cre. Furthermore, the disease was transplantable by MPPs, but not more committed progenitor populations, demonstrating that MDS tumour propagating potential is not exclusive to intrinsically self-renewing HSCs. Targeting Ezh2 and Runx1 inactivation to early lympho-myeloid progenitors did not result in an MDS phenotype. These mice showed a marked expansion of ETPs within the thymus, combined with a block in thymocyte differentiation. These expanded ETPs displayed transcriptional features characteristic of ETP leukaemia, a treatment-resistant acute leukaemia subtype hypothesised to originate from ETPs. Combination of inactivation of Ezh2 and Runx1 in ETPs with the constitutively activating Flt3-ITD signalling mutation resulted in an aggressive lympho-myeloid acute leukaemia, which could be propagated by the expanded ETP population. These findings demonstrate the potential of lympho-myeloid progenitors such as ETPs to become leukaemia stem cells which propagate a disease retaining lympho-myeloid features. We used this novel ETP leukaemia model to explore therapeutic targeting of Ezh2-inactivated ETP leukaemias using inhibitors of the bromodomain and extra terminal (BET) proteins. Aberrant transcription resulting from epigenetic changes induced by Ezh2 loss could be reversed by BET inhibitors, and these compounds showed therapeutic efficacy against both mouse and human ETP leukaemias in vitro and in vivo.
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Mallinson, Gary. "Characterisation of the erythrocyte membrane components which carry the antigens of the LW, Duffy and Cromer blood group systems." Thesis, University of the West of England, Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294721.
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Dyer, Greg Bryan. "Possible effects of HIV infection on overall survival of patients diagnosed with acute myeloid leukaemia." Diss., University of Pretoria, 2019. http://hdl.handle.net/2263/75830.
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Background
The effects of Human Immunodeficiency Virus (HIV) on the Overall Survival (OS) in patients diagnosed with Acute Myeloid Leukaemia (AML) are not well documented. All studies to date have been with small sample sizes and based on collections of case studies from different facilities with different treatment protocols, as a result it has been difficult to draw definitive conclusions.
Method
This retrospective record review of a cohort of AML patients (n=304) treated at a single site between 2000 and 2017 was conducted. Age (16-93 years), gender (Male: n=157 ; Female: n=138), ECOG PS (Eastern Co-Operative Oncology Group Performance Status), FAB (French-American-British) staging, blast count, CD4 count, HIV viral load, financial status, response to treatment as measured on bone marrow biopsy and OS were measured. The OS was compared for HIV status. Further comparisons were conducted in a sub-group where age, ECOG PS and FAB staging were controlled.
Results
210 (69.07%) were HIV negative, 31 (10.1%) were HIV positive, 63 (20.7%) had an unknown HIV status. A statistically significant difference was found between HIV negative and HIV positive groups’ OS (563 vs. 121 days ; P<0.01)(HR 2.02 ; 95% CI 1.36 - 2.99) in the main analysis. This difference was also noted when patients who were not treated for AML were excluded from the comparison (OS, 740 vs 194 days, P<0.01)(HR, 2.10 ; 95% CI 1.26-3.50). In the main analysis mean ECOG PS was better in the HIV negative population compared to the positive population (1.80 vs. 2.06). In the controlled group sub-study, where Age, ECOG PS and FAB staging were controlled, the OS between HIV positive and HIV negative patients was not statistically significant (141 days vs. 121 days) (P=0.17; 95% CI). CD4 counts ranged from 29 – 1416, with a mean CD4 of 432 on presentation. No statistically significant difference could be found between CD4 and OS (HR, 1.0 ; 95% CI 0.99-1.00), possibly due to very few patients presenting with a low CD4 count. HIV Viral Loads ranged from <100 – 106640. Similarly, no statistically significant difference was found between HIV Viral Load and OS (HR 0.99 ; 95% CI 0.99-1.00).
Conclusion
HIV has a negative impact upon the OS of patients with AML. HIV appears to impact on OS as a chronic comorbidity by affecting ECOG PS on presentation, reducing their chance of being treated as well as possibly reducing a patients’ functional reserve. This impact does not appear to be as a result of a direct interaction between the HIV and AML disease processes, as when controlling for other factors that may influence OS there is no statistically significant difference in OS between HIV positive and negative patients.Dissertation (MSc (Medical Oncology))--University of Pretoria, 2019.
This thesis/dissertation is under embargo until September 2023.
Medical Oncology
MSc (Medical Oncology)
Restricted
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Caruana, Saviour. "Studies on arteriosclerotic pathologies, haematology, immunology and lipids of captive Atlantic bluefin tuna." Thesis, University of Stirling, 2014. http://hdl.handle.net/1893/21159.
Full textAbstract:
Commercial capture-based aquaculture of the Atlantic bluefin tuna (ABT), Thunnus thynnus (L.), has been prominent in the Mediterranean for over a decade. Owing to several limitations encountered in working with the species, including its high commercial value, there has been little research carried out relating to this species. The objective of this study was to examine several health parameters of captive ABT. These included an examination of coronary artery lesions, haematology, plasma biochemistry, assessment of immune function and changes in fatty acid (FA) flesh content through the on-growing period. Arteriosclerosis in fish is a pathologic condition of uncertain etiology and involves the main coronary artery in teleosts. Apart from reports of their widespread occurrence in salmonids, they have been described from a restricted number of wild ABT specimens but have not received further attention. This investigation analysed the effect of size and period of net-pen rearing on the prevalence and severity of arteriosclerotic lesions in ABT. Coronary arteries from wild and captive fish were investigated and prevalence was 100 %, but increasing structural degradation was observed with increasing fish size, suggesting that lesions progress throughout the life of the fish. Due to the limited availability of wild specimens, the effect of captivity on arteriosclerosis in ABT could not be adequately quantified, although observations suggest that the farming process has no major effect on arteriosclerotic lesions in ABT. Studies on the haematology, plasma biochemistry and immunology of ABT are limited. Haematological and plasma biochemical indices are useful in animal health assessment but use of these requires the establishment of species-specific ranges. Blood was collected from captive ABT specimens of varying weight (61-361 kg) and the major haematological (n = 45), plasma biochemical (n = 30) and immunological parameters (n = 45) were quantified. Size-based differences were found in haematological indices between experimental sub-groups including increased erythrocyte number and haemoglobin level in smaller ABT. No differences were found in immunological parameters except for total IgM levels, which were higher in the smaller individuals. Preliminary investigations indicated that disease prevalence in captive ABT is very low. Epidermal mucus is an important interface between fish and their environment and comprises immunological components which act as a first barrier against pathogen entry or colonisation. Mucus was collected from captive ABT and analysed for innate immune components. The presence of IgM was detected in the mucus of ABT by an enzyme-linked immunosorbent assay and several different enzymes were detected with an API-ZYM kit assay. Zymography experiments confirmed the presence of protease-like enzymes in the mucus, while enzyme assays quantified alkaline phosphatase, protease, esterase and cathepsin B activities. Lysozyme levels were high. The mucus agglutinated sheep erythrocytes but did not demonstrate complement or bacteriolytic activity. There is restricted information on the fatty acid composition of farmed ABT or how this is influenced when the fish are held under commercial aquaculture conditions. This study investigated the FA composition of farmed ABT, its variation by dorsal muscle region and the correlation between dietary FA composition with that of the fish. Analysis of flesh samples retrieved from farmed ABT did not reveal significant differences in the FA composition of experimental sub-groups irrespective of size, time held in captivity or diet. These results indicate that FA metabolism in ABT is substrate-selective. Gene expression measurements from several organs of ABT showed that expression of Δfad5 and elovl5, genes involved in FA metabolism, were highest in the brain followed by the liver but no expression of these genes was detected in the spleen. The findings of this research address aspects of health evaluation and nutritional status in farmed ABT and are discussed in terms of farming practice. Conclusions from some of these studies suggest that the practice of holding wild-captured stock in cages for periods of up to 18 months does not result in significant impact on ABT.
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Peck, Sarah Jane. "Haematology and Serum Biochemistry of Wild Tasmanian Devils with Devil Facial Tumour Disease." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14904.
Full textAbstract:
The Tasmanian devil (TD) is threatened with extinction by a fatally infectious cancer known as Devil facial tumour disease (DFTD). The objectives of this study were toestablish species reference intervals (RIs) and examine changes that occur in DFTD. Blood samples were collected from wild TDs at multiple sites in Tasmania. Significant age differences were found for ALP, CK, cholesterol, calcium, phosphate, albumin, globulin, albumin: globulin ratio and glucose. Significant differences between sexes were observed for AST, creatinine and potassium. Significant seasonal or reproductive status variation in adult males or breeding females were observed for PCV, haemoglobin, RBC, MCHC, MCH, MCV, neutrophils and lymphocytes, fibrinogen, total plasma protein, AST, ALP, ALT, GLDH, bilirubin, urea, calcium, chloride, total protein, albumin, A:G and glucose. Species RIs and subgroup RIs are provided. Subsequently comparisons were made between clinically healthy, wounded and diseased devils; comparisons among stages of DFTD and between ulcerated and non-ulcerated tumours were made. Increased leukocytes, neutrophils, fibrinogen and platelets as well as decreased lymphocytes, erythrocytes and haemoglobin were observed in DFTD devils. ALP, ALT, GLDH, sodium, Na:K ratio, potassium, albumin and A:G ratio were lower and AST greater in animals with DFTD when compared to clinically healthy animals. No significant differences were found between stages of DFTD or ulcerated and non-ulcerated tumours. Establishing species RIs provides a useful diagnostic tool for health assessment of TDs. The differences with DFTD compared to healthy devils are reflective of inflammation or chronic disease. Similar changes are observed with wounds but to a lesser extent. The lack of significant variation among stages of DFTD and between ulcerated and non-ulcerated tumours was unexpected, and could be due to the lack of information about the extent of tumour necrosis and surface ulceration.
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Ng, Hon-yi, and 吳漢怡. "Evaluation of the new red cell parameters on Beckman Coulter DxH800 automated haematology analyzer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/202311.
Full textAbstract:
Objectives: The new red blood cell (RBC) parameters from automated haematology analyzers, such as reticulocyte haemoglobin content and percentage of hypochromic red cells or equivalent, are useful in the laboratory assessment of iron deficiency anaemia (IDA). However, the clinical utility of these parameters are confounded by thalassaemia trait (TT) especially in geographical areas of high thalassaemia prevalence. We aimed to evaluate the new formula derived from some red cell parameters on the Beckman Coulter DxH800 in distinguishing between IDA and TT in Hong Kong population.
Methods: A total of 246 normal subjects, 102 patients with IDA and 115 subjects with TT were accrued for the study. Concurrent chronic disorder and ovelapped IDA and TT cases were excluded. The new red cell parameters studied were red blood cell size factor (RSF), low haemoglobin density (LHD%), microcytic anaemia factor (MAF), standard deviation of conductivity of the non-reticulocyte population (SD-C-NRET) and unghosted cell (UGC). Comparison between groups was performed by student t-test and the diagnostic performance of the parameters was determined by receiver operating characteristic (ROC) curve analysis.
Results: Both LHD% and RSF were significantly higher in IDA than TT, whereas MAF was significantly lower. Although the biological basis was uncertain, SD-C-NRET was significantly lower in IDA than TT and showed the best diagnostic performance as a single parameter. A formula ((RBC+HB)*(HCT+SD-C-NRET))/(RDW-SD ) was devised to distinguish between IDA and TT. With a cutoff value of 23, the area under curve (AUC) was 0.995 (95% CI of 0.99 – 1.00), the sensitivity was 97% and the specificity was 99.1%. This formula was superior to other discriminant functions in the literature. The UGC number was not significantly different between alpha- and beta-TT.
Conclusions: The new RBC parameters on Beckman Coulter DxH800 provided useful information in distinguishing between IDA and TT, which is important for clinical decision making and streamlining further laboratory testing. This index can be used to screen patients who are likely to be IDA or TT for further hematological studies to confirm diagnosis.published_or_final_version
Pathology
Master
Master of Medical Sciences
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Stefan, Daniela Cristina. "Developing a framework for an undergraduate haematology curriculum in a Faculty of Health Sciences." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/3187.
Full textAbstract:
Thesis (PhD (Curriculum Studies))--University of Stellenbosch, 2010.ENGLISH ABSTRACT: The Faculty of Health Sciences at Stellenbosch University adopted a new set of guidelines for curriculum design in 1997, emphasising an orientation towards the requirements of the public sector general practice, a holistic approach and exposure to community lifestyle and disease patterns specific to various communities. In order to ensure the anchoring in the realities of the general practice, a family medical practitioner, appointed by the Academy of Family Practice, was included in the curriculum control structure of the faculty. It was further recommended that a family medical practitioner should be included in the curriculum committee of each discipline, where appropriate. The present research, starting from the assumption that the opinion of a single family practitioner is insufficient to determine the adequacy of the curriculum for general medical practice, aimed to conduct a comprehensive needs analysis of all stakeholders in the undergraduate haematology training programme at the Faculty of Health, Stellenbosch University, and to compare the findings with the existing curriculum. To this purpose, the opinions of five adult medicine haematologists, ten paediatric haematologists, four laboratory haematologists, ten interns, fourteen students and twenty general practitioners were surveyed. An open-ended questionnaire on the usefulness of the haematology module for hospital and independent general practice was analysed, using the “coding technique” method. On this basis, a list of subjects was drawn and, using a Delphi method, the participants in the study were asked to rate their importance for practice. The answers to the open-ended questionnaires revealed a few overarching concepts, the most important being the need to structure the material taught in the form of “approaches”, supporting the differential diagnosis, which is the most frequent task of a general practitioner. Among the outcomes identified in the panellists‟ answers, the need to adequately detect and assess the “red flag” signs for haematological cancers was proposed for consideration as an outcome in the next curriculum. The Delphi survey indicated a group of subjects which were rated as most important for practice and another group designated as devoid of utility. The remaining subjects, rated as of moderate importance, could be further classified as diseases usually managed by the general practitioner and pathology which would be referred to a specialist for management. These iv findings were compared with the existing curriculum and the discrepancies were analysed, resulting in a set of proposals towards a framework for a new undergraduate haematology curriculum. For the first time in the literature, as far as can be determined, this research presents outcomes and content for an undergraduate haematology course which were defined and rated for importance by consensus of the curriculum developers, specialists in the field and graduates of the course. The methods tested in this process and some of the trends revealed might be useful for curriculum development in other medical disciplines.
AFRIKAANSE OPSOMMING: Die Fakulteit van Gesondheidswetenskappe by die Universiteit Stellenbosch het in 1997 nuwe riglyne vir kurrikulumontwerp aanvaar. Hierdie riglyne beklemtoon `n bewustheid van die behoeftes van algemene praktyk in die openbare sektor, `n omvattende benadering tot en blootstelling aan die gemeenskapslewenstyl, asook aan siektepatrone eie aan verskillende gemeenskappe. Om te verseker dat die kurrikulum in die werklikhede van algemene praktyk geanker bly, is `n algemene praktisyn, aangestel deur die Akademie van Huisartskunde, ingesluit in die kurrikulum beheerstruktuur van die fakulteit. Dit is verder ook aanbeveel dat, waar van toepassing, `n huisarts in die kurrikulumkomitee van elke dissipline ingesluit moet word. Hierdie navorsing, wat van die veronderstelling gespruit het dat die opinie van `n enkele huisarts onvoldoende is om die toepaslikheid van `n kurrikulum vir algemene praktyk te verseker, het ten doel gestel om `n omvattende analise van behoeftes van alle belanghebbendes in die voorgraadse hematologie-opleidingsprogram by die Fakulteit van Gesondheidswetenskappe, Universiteit van Stellenbosch, te doen en om die bevindings met die bestaande kurrikulum te vergelyk. Die menings van vyf volwasse medisyne hematoloë, tien pediatriese hematoloë, vier laboratorium hematoloë, tien huisdokters, veertien studente en twintig algemene praktisyns is verkry. `n Oop-einde vraelys oor die bruikbaarheid van die hematologie-module vir hospitaal- en onafhanklike algemene praktyk is m.b.v die gekodeerde tegniek ontleed. Op grond hiervan is `n lys onderwerpe gekies en studiedeelnemers is deur van die Delphi-metode gebruik te maak, gevra om die graad van belangrikheid van elkeen aan te dui. Die antwoorde op die oop-einde vraelys het `n paar oorkoepelende konsepte uitgelig. Die belangrikste hiervan was om die materiaal wat gedoseer word te struktureer in die vorm van „benaderings‟, wat die vorming van `n differensiële diagnose ondersteun. Lg. is die algemeenste taak van die algemene praktisyn. Een van die uitkomste wat deur die studiedeelnemers geïdentifiseer is, nl. die vermoë om die `rooi vlag` tekens van hematologiese kankers korrek te bespeur en te assesseer, is voorgestel vir oorweging vir insluiting as `n uitkoms in die volgende kurrikulum.
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Walton, Shasheen. "Effects of season and cohort on the haematology of the geometric tortoise Psammobates geometricus." University of the Western Cape, 2012. http://hdl.handle.net/11394/4543.
Full textAbstract:
Magister Scientiae (Biodiversity and Conservation Biology) - MSc (Biodiv and Cons Biol)The geometric tortoise is one of the world‟s rarest terrestrial tortoises and is endemic to the Southwestern Cape, South Africa. There has been cause for conservation concern for Psammobates geometricus, yet as is common for many species, quantitative physiological research has been lacking. Considering the important role of red blood cells in oxygen circulation, and the role of white blood cells in immune resistance, blood profiles have been used across taxa as a reliable indicator of health status and physiological processes. Forming part of a larger chelonian conservation programme in South Africa, I studied the haematological changes in P. geometricus, to better understand their physiological responses to changes in climatic conditions. Sampled peripheral blood from males, females and juveniles of the largest known wild geometric tortoise population over four seasons (spring, summer, autumn and winter) from August 2000 to June 2001. Blood samples were used to make smears and determine red cell count (RCC), packed cell volume (PCV), haemoglobi concentration (Hb), red cell indices and differential white cell counts. Digital imaging analysis was used for the histological evaluation of stained blood smears, including descriptions of red and white blood cell morphologies, as well as erythrocyte developmental stages. In the cooler periods, geometric tortoises showed low Hb and mean cell haemoglobin concentration values. Erythrocytes were larger and rounder in winter and spring, which were likely due to hydration states. In addition, increased numbers of immature erythrocytes in circulation suggested an erythropoietic response in winter and spring. This regenerative response is common in reptiles emerging from periods of limited activity and is associated with increasing primary production following rainfall events. In the following summer and autumn, increased mean cell haemoglobin concentrations suggested elevated metabolic rates influenced by rising temperatures. This would seem pertinent to meet the extra physical demands associated with foraging effort in the season characterised with limited water and food supply, and mating behaviour, which occurs in the summer. Low body conditions across all cohorts provided evidence for nutrition stress, while erythrocyte size, shape and degenerative responses indicated dehydration stress. Physiological responses to seasonal influences are specific to growth or reproductive demands and differed for each cohort. Males experienced increased Hb, PCV, RCC, and erythrocyte sizes in summer and autumn, which relate to the erythropoieticstimulating effects of androgens. Female erythropoietic cycles in spring accommodate the increased metabolic demands of increased foraging needed for a larger body size and egg production, and again in autumn again for vitellogenesis. Juvenile tortoises showed minimal differences, and could indicate species-specific responses to environmental changes. A spring-related erythropoiesis was observed in juveniles while during summer and autumn, juveniles showed less evidence for dehydration stress than in adults. No haemoparasites were observed in peripheral blood. Seven leukocyte types were identified and included heterophils, eosinophils, basophils, lymphocytes, plasma cells, monocytes and azurophils, in addition to thrombocytes. Heterophils were the most abundant leukocyte, followed by lymphocytes and eosinophils while monocytes and basophils were equally low; plasma cells and azurophils were rare. Heterophil counts were higher in spring than in summer and autumn, and in summer, were more abundant in females than in juveniles. Eosinophil counts were low in spring for all cohorts, and additionally, female and juvenile counts were low in summer. Eosinophils in juveniles were significantly lower than in adults in winter and spring. Lymphocyte numbers increased in autumn for all cohorts, while summer counts were higher in juveniles than in adults. Basophils and monocytes showed minimal seasonal changes, although basophil counts in females in winter tended to be high. Thrombocytes were lowest in spring for all cohorts. Understanding the physiological responses associated with seasonal changes and for each cohort is critical for effective chelonian conservation management. Results obtained from this study indicate a clinically healthy population of Psammobates geometricus and represented the first of this kind to establish baseline haematological reference data for this Critically Endangered tortoise species.
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Donoghue, Alan M. "Acute heat illness in underground miners : the clinical state, haematology, biochemistry and risk factors." Thesis, Curtin University, 2000. http://hdl.handle.net/20.500.11937/2196.
Full textAbstract:
Objectives - To examine the incidence, clinical state, personal risk factors, haematology and biochemistry of heat exhaustion cases occurring at a deep underground metalliferous mine. To describe the underground and surface thermal conditions associated with the occurrence of heat exhaustion cases.Methods - A one-year prospective case-series of acute heat exhaustion cases was undertaken at a deep underground metalliferous mine in tropical and Australia. A case-control study of body mass index (BMI) and maximal oxygen uptake (VO(subscript)2max) in heat exhaustion was also undertaken. A history was obtained using a structured questionnaire. Pulse rate, blood pressure, tympanic temperature and urine specific gravity were measured before treatment. Venous blood was analysed for haematological and biochemical parameters, during the acute presentation and after recovery. BMI and VO(subscript)2max were measured after recovery and in a group of controls. Psychrometric wet bulb temperature, dry bulb temperature and air velocity were measured at the underground sites where heat exhaustion had occurred. Air cooling power and psychrometric wet bulb globe temperatures were derived. Surface 24-hour mean wet bulb and dry bulb temperatures were recorded. Surface 24-hour mean wet bulb globe temperatures were derived.Results - 106 cases were studied in the case series. The incidence of heat exhaustion during the year was 43.0 cases per million man-hours. In February it was 147 cases per million man-hours. The incidence rate ratio for mines operating below 1200m compared to those operating above 1200m was 3.17. Mean estimated fluid intake was 0.64 litres/hour (SD 0.29, Range 0.08-1.50).The following were raised on acute presentation compared to recovery (P value, % of acute cases above the normal clinical range): neutrophils (P<0.001, 36%), anion gap (P<0.001, 63%), urea (P<0.001, 21%), creatinine (P<0.001, 30%), glucose (P<0.001, 15%), serum osmolality (P=0.030, 71%), creatine kinase (P=0.002, 45%), aspartate transaminase (P<0.001, 14%), lactate dehydrogenase (P<0.001, 9.5%), and ferritin (P<0.001, 26%). The following were depressed on acute presentation compared to recovery (P value, % of acute cases below the normal clinical range): eosinophils (P=0.003, 3 8%) and bicarbonate (P=0.0 11, 32%). Urea and creatinine were significantly raised in miners with heat cramps compared to miners without this symptom (P<0.001), while there was no significant difference in sodium concentration (P=0.384).Mean psychrometric wet bulb temperature was 29.0 degrees celsius (SD 2.2, Range 21.0-34.0). Mean dry bulb temperature was 37.4 degrees celsius (SD 2.4, Range 31.0-43.0). Mean air velocity was 0.54 m/s (SD 0.57, Range 0.00-4.00). Mean air cooling power was 148 W/m(subscript)2 (SD 49, Range 33-290). Mean psychrometric wet bulb globe temperature was 31.5 degrees celsius (SD 2.0, Range 25.2-35.3). Few cases (<5%) occurred at a psychrometric wet bulb temperature <25.0'C, dry bulb temperature <33.8'C, air velocity >1.56 m/s, air cooling power >248 W/m(subscript)2, or psychrometric wet bulb globe temperature <28.5 degrees Celsius.The three surface temperature variables were significantly higher on those days on which heat exhaustion occurred compared to those days on which it did not occur (P<0.001). The relative risk of heat exhaustion on days when the surface 24-hour mean wet bulb globe temperature was in the range 26.0-28.0 degrees celsius was 4.82 (95% CI 2.12-10.96).65 cases of heat exhaustion and 119 controls were studied in the case-control study. Heat exhaustion cases had a significantly higher BMI than controls (P=0.006). The odds ratios increased with BMI. For a BMI of 32.00-36.99, compared to a BMI of less than 27.00 the odds ratio was 3.63 (95% confidence interval 1.42-9.36). V0(subscript)2max was not significantly lower in cases than controls. The odds ratios for heat exhaustion increased with decreasing VO(subscript)2max, but not significantly. The sample size provided 80% power of detecting an odds ratio of 2.5 or greater.Conclusion - Heat exhaustion in underground miners is associated with hypohydration, neutrophil leukocytosis, eosinopenia, metabolic acidosis, increased glucose and ferritin, and a mild rise in CK, AST and LD. Heat cramps are associated with hypohydration but not hyponatraemia. The incidence of heat exhaustion increases during summer and at depth. An increased fluid intake is required. Heat exhaustion would be unlikely to occur if ventilation and refrigeration achieved air cooling power >250W/m2 at all underground work sites. Surface temperature data could be used at this mine to warn miners about the risk of heat exhaustion. Deep underground miners should be advised to maintain a BMI of 24-27.
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Donoghue, Alan M. "Acute heat illness in underground miners : the clinical state, haematology, biochemistry and risk factors." Curtin University of Technology, School of Public Health, 2000. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=11757.
Full textAbstract:
Objectives - To examine the incidence, clinical state, personal risk factors, haematology and biochemistry of heat exhaustion cases occurring at a deep underground metalliferous mine. To describe the underground and surface thermal conditions associated with the occurrence of heat exhaustion cases.Methods - A one-year prospective case-series of acute heat exhaustion cases was undertaken at a deep underground metalliferous mine in tropical and Australia. A case-control study of body mass index (BMI) and maximal oxygen uptake (VO(subscript)2max) in heat exhaustion was also undertaken. A history was obtained using a structured questionnaire. Pulse rate, blood pressure, tympanic temperature and urine specific gravity were measured before treatment. Venous blood was analysed for haematological and biochemical parameters, during the acute presentation and after recovery. BMI and VO(subscript)2max were measured after recovery and in a group of controls. Psychrometric wet bulb temperature, dry bulb temperature and air velocity were measured at the underground sites where heat exhaustion had occurred. Air cooling power and psychrometric wet bulb globe temperatures were derived. Surface 24-hour mean wet bulb and dry bulb temperatures were recorded. Surface 24-hour mean wet bulb globe temperatures were derived.Results - 106 cases were studied in the case series. The incidence of heat exhaustion during the year was 43.0 cases per million man-hours. In February it was 147 cases per million man-hours. The incidence rate ratio for mines operating below 1200m compared to those operating above 1200m was 3.17. Mean estimated fluid intake was 0.64 litres/hour (SD 0.29, Range 0.08-1.50).The following were raised on acute presentation compared to recovery (P value, % of acute cases above the normal clinical range): neutrophils (P<0.001, 36%), anion gap (P<0.001, 63%), urea (P<0.001, ++21%), creatinine (P<0.001, 30%), glucose (P<0.001, 15%), serum osmolality (P=0.030, 71%), creatine kinase (P=0.002, 45%), aspartate transaminase (P<0.001, 14%), lactate dehydrogenase (P<0.001, 9.5%), and ferritin (P<0.001, 26%). The following were depressed on acute presentation compared to recovery (P value, % of acute cases below the normal clinical range): eosinophils (P=0.003, 3 8%) and bicarbonate (P=0.0 11, 32%). Urea and creatinine were significantly raised in miners with heat cramps compared to miners without this symptom (P<0.001), while there was no significant difference in sodium concentration (P=0.384).Mean psychrometric wet bulb temperature was 29.0 degrees celsius (SD 2.2, Range 21.0-34.0). Mean dry bulb temperature was 37.4 degrees celsius (SD 2.4, Range 31.0-43.0). Mean air velocity was 0.54 m/s (SD 0.57, Range 0.00-4.00). Mean air cooling power was 148 W/m(subscript)2 (SD 49, Range 33-290). Mean psychrometric wet bulb globe temperature was 31.5 degrees celsius (SD 2.0, Range 25.2-35.3). Few cases (<5%) occurred at a psychrometric wet bulb temperature <25.0'C, dry bulb temperature <33.8'C, air velocity >1.56 m/s, air cooling power >248 W/m(subscript)2, or psychrometric wet bulb globe temperature <28.5 degrees Celsius.The three surface temperature variables were significantly higher on those days on which heat exhaustion occurred compared to those days on which it did not occur (P<0.001). The relative risk of heat exhaustion on days when the surface 24-hour mean wet bulb globe temperature was in the range 26.0-28.0 degrees celsius was 4.82 (95% CI 2.12-10.96).65 cases of heat exhaustion and 119 controls were studied in the case-control study. Heat exhaustion cases had a significantly higher BMI than controls (P=0.006). The odds ratios increased with BMI. For a BMI of 32.00-36.99, compared to a BMI of less than 27.00 the odds ratio was 3.63 (95% ++
confidence interval 1.42-9.36). V0(subscript)2max was not significantly lower in cases than controls. The odds ratios for heat exhaustion increased with decreasing VO(subscript)2max, but not significantly. The sample size provided 80% power of detecting an odds ratio of 2.5 or greater.Conclusion - Heat exhaustion in underground miners is associated with hypohydration, neutrophil leukocytosis, eosinopenia, metabolic acidosis, increased glucose and ferritin, and a mild rise in CK, AST and LD. Heat cramps are associated with hypohydration but not hyponatraemia. The incidence of heat exhaustion increases during summer and at depth. An increased fluid intake is required. Heat exhaustion would be unlikely to occur if ventilation and refrigeration achieved air cooling power >250W/m2 at all underground work sites. Surface temperature data could be used at this mine to warn miners about the risk of heat exhaustion. Deep underground miners should be advised to maintain a BMI of 24-27.
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Fegan, C. D. "The gut mucosal barrier following bone marrow transplantation." Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308776.
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AlSaeed, Abbas Habeeb. "The application of flow cytometeric and fluorescent microscopic techniques to the study of multiple myeloma." Thesis, University of Sheffield, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296727.
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Prinsloo, T. "The evaluation of a new haematological cell counter, the CELL-DYN 3500, on canine leukocyte differential counts." Diss., University of Pretoria, 2001. http://hdl.handle.net/2263/23383.
Full textAbstract:
Please read the abstract in the section 00 front of this documentDissertation (M Med Vet (Clinical Laboratory Diagnostics))--University of Pretoria, 2001.
Companion Animal Clinical Studies
unrestricted
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Facchini, Raffaella Maria. "Investigating the specific roles of the growth factor kit ligand in the regulation of murine haematopoiesis." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:35da4965-5da9-4007-bf97-8408f0f5ed06.
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Maybury, Helena. "The characterisation of global haemostatic function during pregnancy and the puerperium using thromboelastography." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/10236.
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Chowdhury, Onima. "Characterisation and targeting of stem cells in myelodysplastic syndromes." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:741c2079-c6b3-46dc-b4d2-5708693e6cb3.
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Understanding which cells within a cancer are responsible for its initiation and propagation is vital if we are to achieve cure. If cancer stem cells are the only population able to sustain a tumour long term, designing therapeutic strategies to target this population will give medical science the best chance of long-term cure. Significant controversy remains over the existence of cancer stem cells, predominantly due to the lack of a sensitive human cancer stem cell assay. This thesis investigates whether two haematological malignancies, myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) can only be driven by rare and distinct cancer stem cells. We have demonstrated that low and intermediate-1 risk MDS is driven solely by the stem cell (Lin- CD34+ CD38- CD90+ CD45RA-) by developing a novel genetic approach, tracing all somatic mutations and karyotypic abnormalities back to this population. Prior to this study, very little was known about the clonal architecture of CMML. By performing detailed phenotypic, functional, molecular and genetic analysis of patients with CMML, we were able to demonstrate that the most likely candidate driver cell in these patients was also the stem cell rather than any of the down-stream progenitors. Currently, effective therapeutic strategies for MDS or CMML are very limited. Allogeneic stem cell transplantation is the only potential cure and not suitable for most patients. Cancer stem cells, including MDS stem cells are known to be highly quiescent and selectively resistant to therapy. Having demonstrated that both MDS and CMML were driven by stem cells, we developed a novel therapeutic targeting strategy. Using the thrombopoietin receptor agonist, Romiplostim, we were able to activate stem cells and enhance their subsequent sensitivity to chemotherapy dramatically. This approach may facilitate improved remission rates and prevent cancer stem cell driven relapse in many diseases.
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Mussai, Francis Jay. "Immunotherapy and immunomodulation for haematological malignancies." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:6120e659-0dab-4447-b4d6-75e235d3b2c8.
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HA22 is an immunotoxin composed of an anti-CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A. The mechanisms of cytotoxicity and resistance of HA22 against Acute Lymphoblastic Leukaemia (ALL) and Burkitt’s lymphoma were studied. Using a bone marrow mesenchymal cell culture assay to support ALL cell viability, I? investigated the in vitro cytotoxicity of HA22 against ALL blasts from newly diagnosed and relapsed patients. There was interpatient variability in sensitivity to HA22. There was no significant difference in HA22 sensitivity between diagnosis and relapse samples but peripheral blood ALL blasts were more sensitive to HA22 than those from bone marrow. The mechanisms of resistance to HA22 were studied, using cell lines as a model. The number of CD22 sites/ cell and the rates of immunotoxin internalisation did not affect HA22 cytotoxicity. HA22 mutants with resistance to lysosomal degradation and enhanced targeting to the endoplasmic reticulum had improved cytotoxicity. The role of apoptosis pathways proteins in HA22-mediated cell death was studied. Their role is complex but raised levels of the anti-apoptotic pathway protein Bcl-2 were found in the most resistant NALM6 cell line. Penetration of HA22 into Burkitt’s lymphoma masses was studied using a flow cytometric based method. HA22 rapidly penetrated into the lymphoma masses, however a barrier to further uptake is present which could not be overcome by the addition of adriamycin or taxol in the murine xenograft model. The ability of Acute Myeloid Leukaemia (AML) blasts to create an immunosuppressive niche was investigated using a cell line model and primary patient samples. AML blasts suppress T cell proliferation through altered arginine metabolism, dependent on the enzymes arginase II and iNOS. Small molecule inhibitors to arginase and iNOS restored T cell proliferation in vitro. AML further enhances its immunosuppressive niche by transforming surrounding monocytes into an M2-immunosuppressive phenotype, in an arginase dependent manner. The immunomodulatory protein Serum Amyloid A (SAA) was secreted by AML blasts, and leads to AML chemotaxis, IL-1production, and release of S100A9 protein. Finally, invariant Natural Killer T cells (iNKT) were shown to be cytotoxic to some AML blasts, in the presence of Galactosylceramide, and thus able to restore T cell proliferation. The results provide a strong rationale for the clinical testing of these novel immunotherapeutic and immunomodulatory strategies in patients with haematological malignancies.
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Yeghen, Tullie. "Diagnosis and epidemiology of Aspergillus fumigatus and Aspergillus flavus infections by molecular techniques in haematology patients." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395541.
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Wolmarans, Wilhelm J. "The effect of transport on live weight loss, meat quality and blood haematology in slaughter ostriches." Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6762.
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Thesis (MScAgric (Animal Sciences))--University of Stellenbosch, 2011.ENGLISH ABSTRACT: The production and export of ostrich meat from southern Africa, to especially the European Union, are increasing rapidly due to the healthy nature of ostrich meat. The European Union has very high standards when importing food products, and it is inevitable that more emphasis is being placed on the production of high quality ostrich meat. Another aspect also of concern to consumers, is the welfare of animals prior to slaughter, and this forces producers to look at ways to decrease stress of animals during the ante-mortem period. Research regarding the effect of stress during the ante-mortem period, and as a result, on meat quality, haematology and weight loss in ostriches, is lacking and thus the purpose of this study was to investigate the effect of various transport distances, travel conditions and different birds on these factors. Ante-mortem stress was measured using serum corticosterone levels (ng/ml), heterophil: lymphocyte (H:L) ratio, white blood cell (WBC) count, aspartate aminotransferase (AST) and creatine kinase (CK), as well as the rate and extent of pH decline in the M. gastrocnemius. Special emphasis was also placed on the meat quality parameters drip loss, cooking loss, colour and Warner-Bratzler shear force (kg/1.27 cm diameter). Live weight losses, as well as carcass weight and weight of bruises cut off from each bird were also recorded during various stages of the trials. The effect of transport distance on the meat quality of ostriches was investigated. Ultimate pHu measurements were taken at 24 hours post-mortem. The muscles of the ostriches from the control group (i.e. birds that were not transported prior to slaughter) had a lower mean pHu (5.77 ± 0.053) than birds that travelled 60 (5.93 ± 0.053) and 600 km (6.11 ± 0.053), respectively. Differences in meat drip loss percentage were also observed between the three treatments. The birds in the control group (0.40 ± 0.07 %) had the lowest meat drip loss percentage compared to the birds that travelled 60 km (treatment C) (1.36 ± 0.07 %) and 600 km (treatment B) (0.97 ± 0.07 %), respectively, to a commcerical ostrich abattoir. Ostriches that were transported for 600 km (8.13 ± 1.16 %) had a greater percentage live weight loss during the antemortem period than birds that travelled a distance of 60 km (2.4 ± 2.185 %) to the abattoir, although both groups were deprived of feed for the same period. When the haematology of the groups that travelled different distances was compared at various time intervals in the ante-mortem period, both groups of birds experienced significant increases in WBC, s-AST and s-CK. An increased H:L ratio from pre-transport to post-transport was only evident in the birds that travelled 600 km (treatment B). However, the birds that travelled 60 km were the only group of birds that had significant elevated serum corticosterone levels during the ante-mortem period. The increase in the various blood parameters indicates severe physical stress, which negatively affected meat quality. Another trial also investigated the effect of various farming systems and transport on meat quality and bruising of ostrich carcasses. Ostriches were raised in three different farming systems, i.e. feedlot -, semiintensive - and free range conditions. Other factors that could maybe impact on stress susceptibility, such as road conditions, floorspace and floor type were also investigated. A significant difference in meat pHu was found between ostriches that were raised in a feedlot (5.95 ± 0.018) and semi-intensive (6.04 ± 0.033) environment. The feedlot birds also had the greatest percentage of carcass weight removed due to bruising. The free range birds were the birds that had the lowest floor density per birds and also had the least amount of bruising on their carcasses. Incidently the other two groups (feedlot and semi intensive) were the birds that travelled on the same type of road (mountain pass) in a truck with rubber flooring whilst the free range birds travelled on a straight road in trucks with metal grid floors.The results indicate that the type of farming system didn’t have a significant influence on meat quality of ostriches, but that factors such as road conditions, flooring and bird density did play a significant role in the incidence of bruises and injuries obtained during transport.
AFRIKAANSE OPSOMMING: Die produksie en uitvoer van volstruisvleis vanuit suidelike Afrika, na veral die Europese Unie, is gedurig aan die toeneem as gevolg van die gesonde aard van volstruisvleis. Die Europese Unie het baie hoë standaarde wanneer dit kom by die invoer van voedselprodukte en dit is onvermydelik dat meer klem op die produksie van hoë gehalte volstruisvleis gelê word. ʼn Ander aspek wat ook kommer wek by verbruikers is die welstand van diere voor slagting en hierdie aspek noodsaak produsente om te kyk na maniere om stres te beperk tydens die periode voor slagting. Navorsing rakende die effek van stres tydens die ante-mortem periode, asook vleiskwaliteit, hematologie en gewigsverlies in volstruise as gevolg van vervoer, ontbreek. Die doel van die studie was dus om die invloed van verskillende vervoerafstande, vervoersomstandighede en tipe produksiesisteme op volstruise se stresrespons te ondersoek. Die omvang van ante-mortem stres is bepaal deur die serum-kortikosteroon vlakke (ng/ml), heterofiel: limfosiet (H:L) ratio, witbloedsel (WBS) telling, aspartaat aminotransferase AST en creatien kinase CK, asook die tempo en vlak van pH-daling in die M. gastrocnemius, te meet. Spesiale klem is gelê op die vleisgehalte parameters kookverlies, drupverlies, kleur en Warner-Bratzler-skeurwaardes (kg/1.27 cm deursnee). Gewigsverlies is aangeteken op verskillende stadiums tydens die proewe. Karkasgewigte en die hoeveelheid gewig afgesny van elke volstruiskarkas a.g.v. kneusings is ook bepaal. Die eerste studie het die invloed van vervoerafstand op vleiskwaliteit van slagvolstruise ondersoek. Vleis kwaliteit parameters soos pH, drip verlies, kook verlies, taaiheid en kleur is ondersoek. Die pHu metings is op 24 uur post-mortem geneem. Slagvolstruise in die kontrole groep (d.i. -volstruise wat nie voor slagting vervoer is nie) het ’n laer vleis pHu (5.77 ± 0.05) gehad as voëls wat onderskeidelik 60 km (5.93 ± 0.05) en 600 km (6.11 ± 0.05) ver vervoer is. Verskille in persentasie dripverlies is gesien tussen die vleis van die voëls wat nie vervoer is nie (0.40 ± 0.07 %) en die voëls wat 60 km (1.36 ± 0.07 %) en 600 km ver (0.97 ± 0.07 %) onderskeidelik vervoer is. Volstruise wat vir 600 km (8.13 ± 1.16 %) vervoer is, het ‘n groter persentasie lewende gewig tydens die ante-mortem periode as voëls wat 60 km (2.4 ± 2.19 %) ver vervoer is na die abattoir, verloor, al was beide groepe weerhou van voer vir dieselfde tydperk. Beide groepe wat vervoer is (60 en 600 km) het merkbare toenames in witbloedsel (WBS) tellings, s-AST’s en s-CK’s getoon tydens die ante-mortem periode. Daar is slegs ʼn toename in H:L ratio (ʼn indikator van stres) van voor vervoer tot na vervoer gesien in die voëls wat 600 km vervoer is. Daarteenoor was die voëls wat slegs 60 km vervoer is die enigste voëls wat ʼn toename in korticosteroon vlakke getoon het gedurende die ante-mortem periode. Die toenames is heel moontlik ‘n aanduiding van erge fisiese stres wat ‘n negatiewe effek op vleiskwaliteit het. Die tweede studie het die effek van verskillende produksiesisteme en die stress respons van die verskillende groepe slagvolstuise op vervoer ondersoek. Vleis kwaliteit parameters soos pH, drip verlies, kook verlies en taaiheid is ondersoek. Die hoeveelheid kneusings per volstruis is ook gemeet. Daar was ‘n beduidende verskil (P = 0.009) tussen die pHu van die voerkraal (5.95 ± 0.018) en semi- intensiewe (6.04 ± 0.033) volstruise. Die voerkraal volstruise se vleis het die grootste drip- en kookverliese gehad in vergelyking met die ander twee groepe (semi-intensiewe en ekstensiewe) terwyl die ekstensiewe volstruise die taaiste vleis gehad het. Die voerkraalvoëls het ook die grootste persentasie karkasgewig verloor a.g.v. kneusings wat afgesny is. Die ekstensiewe voëls het die laagste vloer digtheid per volstruis gehad asook die minste kneusings. Die ander twee groepe (voerkraal en semi intensief) was die groepe wat op dieselfde pad vervoer is (bergpas) in vragmotors wat rubber vloere gehad het terwyl die ekstensiewe voêls op ‘n reguit pad vervoer is in ‘n vragmotor met ‘n metaal oppervlakte. Die resultate van die studie is ‘n aanduiding dat die tipe plaassisteem nie ‘n groot impak op die hoeveelheid akute stres ervaar deur die voëls tydens vervoer gehad het of gevolglik op die vleiskwaliteit van die volstruise nie, maar dat faktore soos pad toestand, tipe vloer en voëldigtheid wel ‘n wesenlike rol speel in die voorkoms van kneusings en beserings opgedoen tydens vervoer.
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no, nicolai@bonne, and Nicolai Johnsen Bonne. "Psittacine beak and feather disease : vaccination, haematological response and pcr methodology." Murdoch University, 2010. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20100211.182512.
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To enable assessment of recombinant BFDV capsid protein (recBFDVcap) for vaccination to protect against PBFD, commercially available lovebirds (Agapornis sp.) were tested for evidence of past and current BFDV infection using PCR, HI and HA to identify suitable BFDV-free birds in which to test the vaccine. During this attempt, it was found that lovebirds from commercial aviaries were endemically infected with BFDV with evidence of up to 100% prevalence of BFDV DNA in blood samples from individual birds over time. Such an approach was abandoned as unlikely to yield suitable numbers of naïve birds to conduct a BFDV vaccination trial.
As commercially available lovebirds were considered to be a poor source of BFDV-free birds, wild caught cockatoo nestlings and eggs (long-billed corella; Cacatua tenuirostris and galah; Eolophus roseicapillus) were used to assess the efficacy of BFDV vaccination using baculovirus recombinant BFDV capsid. Eggs were artificially incubated and 3 eggs successfully hatched and 1 was successfully hand-reared. All nestlings were screened for BFDV DNA in blood using PCR upon arrival then on days 11, 18 and 25 and tested for anti-BFDV antibody on the day of arrival. All hatched birds were determined to be free of BFDV DNA and BFDV HI antibody in the peripheral blood throughout the hand rearing period and the flock was considered to be suitable for a BFDV vaccination trial.
Corellas (n=13) were injected with 1 mL of vaccine containing 10 μg recBFDVcap on day 0 and 0.4 mL vaccine containing 66.8 μg recBFDVcap on day 11. All vaccinated corellas and 5 non-vaccinated control corellas were given 0.4 mL BFDV suspension (titre = log2 12 HAU/50 μL) intramuscularly and 0.1 mL orally 16 days after booster vaccination. Blood was collected periodically during the vaccination period and blood and feathers collected before and after BFDV administration. Testing included BFDV DNA detection by PCR and qRT PCR (on blood) as well as serum antibody detection by haemagglutination inhibition (HI) and BFDV DNA and antigen was detected by qRT PCR and haemagglutination (HA) (on feathers), respectively. Four of 97 blood samples collected from vaccinated birds post BFDV challenge tested positive by PCR, whereas 17 of 35 samples taken from non-vaccinated control corellas tested positive. Vaccinated birds did not develop feather lesions, had only transient PCR detectable viraemia and had no evidence of persistent infection 270 days post-challenge using PCR, histopathology and immunohistochemistry (IHC). Non-vaccinated control corellas developed transient feather lesions and PCR, HI and HA test results consistent with PBFD. They were BFDV PCR positive for up to 41 days post-challenge and qRT PCR demonstrated reduced virus replication in vaccinated birds compared to non-vaccinated control birds. Thus, administration of recBFDVcap vaccine alone was found to incite an adaptive immune response in BFDV-free corellas that subsequently conferred protection against inoculation with BFDV.
A commonly utilized method for excising blood dried on filter paper was proven to be of high risk of carryover contamination facilitated by a hole punch used for processing several samples. Therefore a practical method of avoiding carryover contamination was developed and used in the DNA testing procedures of the vaccination trial.
Finally, the haematological characteristics of the above mentioned cockatoos were studied before and for 97 days after experimental infection with BFDV. It was found that the pre-challenge haematological values were similar between the vaccinated and non-vaccinated corellas. Most pre-challenge parameters were comparable to previously reported values of other cockatoos and psittacine birds. Significant differences were seen in both groups when comparing pre-challenge values with post challenge values for total and differential leukocyte concentrations, but PCV and TSP were not significantly affected by BFDV challenge.
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Sparks, Sharna. "Blood cell histology of Homopus areolatus: effects of season and cohort." University of the Western Cape, 2015. http://hdl.handle.net/11394/4776.
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Magister Scientiae (Biodiversity and Conservation Biology)Homopus areolatus is an endemic terrestrial tortoise that resides in a Mediterranean type of climate, which is characterised by winter rainfall and mild winter temperatures. Within ectotherms, such as H. areolatus, physiological changes are elicited by changes in the ambient temperature. These physiological changes are evident in the blood profile of reptiles. I described the morphology of immature and mature erythrocytes, leukocytes as well as thrombocytes of H. areolatus. Additionally, I evaluated erythrocytes, leukocytes and thrombocytes to assess the effects of season and cohort on these cells. Blood samples were collected in 2000 and 2001 at Elandsberg Nature Reserve in the Western Cape from H. areolatus cohorts (female, male, juvenile) in all seasons (spring, summer, autumn, winter). Blood smears were made and stained with modified Giemsa stain. SigmaStat was used for all statistical analysis. Immature erythrocyte types within H. areolatus included basophilic rubricytes, polychromatophilic rubricytes and polychromatophilic erythrocytes. Upon my evaluation, I encountered evidence to suggest that small and large immature erythrocytes possibly developed from two distinctive lineages. Further research is required to discern which lineage gave rise to which immature erythrocyte type. Cohort had no effect upon immature erythrocytes. Erythropoiesis was most prevalent during winter and spring within H. areolatus. Aberrant features of erythrocytes appeared to be more prevalent during autumn, which signified the driest season with limited food and water. Mature erythrocytes play a huge role in oxygen transport and metabolism in individuals. Factors such as size and shape are relevant since small, mature, ellipsoidal erythrocytes transport oxygen more efficiently than large, spherical erythrocytes. In H. areolatus small, mature, ellipsoidal erythrocytes appeared to be most prevalent during spring and summer. During winter however, large, spherical erythrocytes appeared to be most prevalent. Thrombocytes and seven types of leukocytes were observed within H. areolatus, namely heterophils, lymphocytes, eosinophils, basophils, monocytes, plasma cells and azurophils. Among cohort and season heterophils were most prevalent overall, followed by lymphocytes and eosinophils respectively. Basophils, monocytes, plasma cells and azurophils were present but overall, were relatively few. H. areolatus appeared to be healthy, and leukocyte counts as well as its dimensions appeared to be in accordance with other reptilian studies. This study serves as the first baseline haematological reference forH. areolatus. The study forms the second of its kind on South African tortoises, only one other haematological study has been done namely, P. geometricus which is a sympatric species to H. areolatus.
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Brandimarti, Maquel E. "Using haematology and biochemistry to investigate the health and evolutionary biology of eastern grey kangaroos (Macropus giganteus)." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/26627.
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Land clearing has detrimental and long-lasting impacts on natural ecosystems and biodiversity, yet land clearing is accelerating world-wide. The eastern grey kangaroo (Macropus giganteus) is a large common macropod that can reach high densities on cleared land. Despite their apparent success, kangaroo populations are susceptible to food shortages and increased disease risk. Developing a broad understanding of the drivers of kangaroo health is required to establish a benchmark to study poor health.
This thesis aimed to develop an evidence-based tool that characterises kangaroo health. Species-specific haematological reference intervals (RI) were developed using blood samples collected from up to 245 animals from four sites across New South Wales and the Australian Capital Territory. Results showed that abiotic factors are critical determinants of kangaroo health outcomes.
A health investigation was then performed, utilising the developed RIs, on a population of kangaroos in which health and welfare issues. This kangaroo population was from Look At Me Now Headland (LAMN) in NSW and was found to have widespread disease (parasitism and non-regenerative anaemia) and nutritional deficiencies stemming from a high population density, prolonged drought and reduced grazing habitat.
The risk factors associated with parasitism were explored by examining potential selection pressures driving the evolution of kangaroos. An experiment was done to examine the influence of testosterone suppression on health parameters, parasite burdens and movement patterns in male kangaroos. While there was no effect of testosterone on these factors during the ten-week suppression period, a trend for reduced parasite burdens in kangaroos with supressed testosterone was evident. The findings of this thesis emphasise that regional planning must consider habitat connectivity for kangaroo populations to prevent overabundance and enhance positive outcomes for the health and welfare of the species.
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Moller, Cheryl. "The haematology of bobtail lizards (Tiliqua rugosa) in Western Australia: reference intervals, blood cell morphology, cytochemistry and ultrastructure." Thesis, Moller, Cheryl (2014) The haematology of bobtail lizards (Tiliqua rugosa) in Western Australia: reference intervals, blood cell morphology, cytochemistry and ultrastructure. Masters by Research thesis, Murdoch University, 2014. https://researchrepository.murdoch.edu.au/id/eprint/22862/.
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Bobtail lizards (Tiliqua rugosa) are native to Western Australia. Haematological evaluation is useful for health assessment: the only previous study of the haematology of this species sampled just six lizards (Canfield and Shea, 1988). The main aim of this study was to produce reference intervals for bobtail haematology.
Over the summers of 2011/12 and 2012/13, heparinised venous blood was collected from 46 clinically healthy, captive adult bobtails in Perth. Complete blood counts and blood smear evaluations were performed. Cytochemical stains, transmission electron microscopy, and bone marrow cytology and histology facilitated further characterisation of the blood cells. Reference intervals with 90% confidence intervals were determined using Reference Value Advisor freeware (Geffré et al., 2011). The packed cell volume (PCV) was 0.10-0.44L/L (n=40). Total plasma protein by refractometry was 36-74g/L (n=39). Haemoglobin was 20-154g/L (n=32). The manual red and white blood cell counts were 0.28-1.03x1012/L (n=38) and 2.75-30.76 x109/L (n=39), respectively.
Blood cell morphology was similar to that of other lizards - except the eosinophils which were uniformly vacuolated. A 200 cell leukocyte differential count was performed on each smear (n=46). Heterophils predominated (27-88%), with fewer lymphocytes (0-34%) and monocytes (1-27%), occasional eosinophils (0-22%) and basophils (0-20%). Thrombocytes were frequently clumped or present as bare nuclei. Slight polychromasia (0-7%) was typically present (n=45).
Many reference intervals were wide, particularly PCV, haemoglobin and white blood cell count. This was not unexpected as reptile haematology is influenced by many preanalytical factors.
Smears from 13 bobtails contained haemogregarine parasites, identified as probable Hemolivia species. There was evidence that this infection caused mild erythrocyte pathology.
The reference intervals were applied to the haematology of seven bobtails hospitalised with upper respiratory tract disease. Six bobtails possessed haematological evidence of inflammation. Thus the reference intervals appear to be clinically useful for the haematological assessment of captive bobtail lizards.
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Philpott, Nicola Jane. "Apoptosis and the pathogenesis of aplastic anaemia." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359983.
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Wong, Kah-Keng. "Validation of lymphoma-associated antigens identified using autoantibody profiling and protein arrays." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:51ac6bbe-2845-43cc-9b7a-cb92097155f1.
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Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma subtype with heterogeneous clinical outcome and a significant number of patients still die of their disease. Characterising lymphoma patients’ autoantibody repertoires represent one approach to improve the understanding of their disease biology. Our hypothesis was that characterisation of antigens eliciting humoural immune responses in lymphoma patients may provide insights into mechanisms of lymphomagenesis and identify novel diagnostic/therapeutic targets. HIP1R was validated as a novel B-NHL autoantigen by immunoblotting with patients’ sera. No response was identified to the related HIP1 protein. Consistent with this finding, more widespread expression of HIP1R, compared to HIP1, was observed in lymphoma cell lines. Expression studies, at both transcript (qRT-PCR and analysis of microarray datasets) and protein levels (blotting and immunolabelling), identified abundant HIP1R in normal B cells and low level expression in a poor prognosis activated B-cell (ABC)-like DLBCL subtype. Upregulation of HIP1R expression was observed in activated non-malignant B cells at both transcript and protein levels, suggesting that downregulation of HIP1R expression in ABC-DLBCL might be a disease-related process. Despite its potential for DLBCL subtyping, HIP1R protein expression was not statistically significantly associated with patients’ survival in a series of 256 DLBCL. Short FOXP1 isoforms were identified as one mechanism repressing HIP1R transcription in an ABC-DLBCL cell line. Phenotypic analysis of HIP1R-depleted B-cell lymphoma cells indicated that HIP1R silencing could increase the surface levels of B-cell receptor (BCR) components such as IgM and CD79b. HIP1R represents a novel lymphoma autoantigen and cell-of-origin marker for distinguishing germinal centre- versus ABC-DLBCL subtypes. As ABC-DLBCL survival is dependent on chronic BCR signalling, future studies will address whether HIP1R silencing plays a fundamental role in disease pathogenesis by promoting BCR signalling.
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Lutteropp, Michael. "The emergence and early fate decisions of stem and progenitor cells in the haematopoietic system." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:eef3e876-bde2-4114-8ac2-bf0c87492a55.
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The alternative road map describes the separation of lympho-myeloid and myeloid-megakaryocyte-erythroid (myeloid-Mk-E) lineages as the earliest haematopoietic commitment event. However, a number of aspects of this lineage restriction process remain poorly understood. Herein this work identified a lympho-myeloid restricted progenitor in the embryo, which resembles the adult LMPP, and demonstrated that lymphoid lineage restriction is initiated prior to definitive haematopoiesis, much earlier than previously appreciated. In vivo fate mapping showed that lympho-myeloid progenitors significantly contribute to steady state myelopoiesis in the embryo. The early thymic progenitor (ETP) as most primitive cell in the thymus was characterised and demonstrated to sustain B, T and myeloid but not Mk potentials at the single cell level. The ETP therefore largely resembles the cellular properties of lympho-myeloid progenitors in bone marrow and foetal liver, which points to these cells as candidate thymus seeding progenitors (TSP). Furthermore the existence of a putative Mk progenitor was explored within the LSKCD150+CD48+Gata1pos compartment of a Gata1 reporter mouse providing the basis for a future prospective characterisation. Finally, this work evaluated the earliest lineage restriction of von Willebrand factor (Vwf)-EGFP+ and EGFP- haematopoietic stem cells (HSCs) through in vitro paired daughter fate mapping. Single Vwf+ HSCs showed heterogeneous Mk priming and more frequently sustained Mk potential after cell division. Moreover, analysis of lineage priming between daughter cells revealed the asymmetric expression of key lineage determinants and stem cell regulators, which might be employed as reporters for future fate mapping studies.