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Biomedical subjects

S E Kinsey

Publications and source records attributed to S E Kinsey.

At least 37 records · Page 2Linked to original sources
PubMed1999

Assessment of Herpesvirus saimiri as a potential human gene therapy vector.

Herpesvirus saimiri has characteristics that make it amenable to development as a gene therapy vector. The viral genome is thought to be capable of accommodating large quantities of heterologous DNA while the virus itself can infect many different cell types. Virus infection has been shown in many cases to be persistent by virtue of episomal maintenance in the target cell. In this article we examine the ability of nonselectable recombinant viruses expressing the beta-galactosidase gene product to infect a variety of human cells and demonstrate that this virus could be developed as an alternative hematopoietic stem cell gene therapy vector. In contrast to earlier observations, we demonstrate by a number of methods that the virus has the ability to replicate in many human cell types, suggesting the need for the development of a disabled virus for use as a gene therapy vector.

Blotting, Southern↗
PubMed1998

Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P < 0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9 to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other cell types within the bone marrow. From examination of the effects of blood sample processing on circulating VEGF concentrations, it is apparent that for accurate measurements, citrated plasma processed within 1 h of venepuncture should be used. Serum is completely unsuitable. The presence of VEGF within platelets has implications for processes involving platelet and endothelial cell interactions. e.g. wound healing, and in tumour metastasis, when platelets adhering to circulating tumour cells may release VEGF at points of adhesion to endothelium, leading to hyperpermeability and extravasation of cells.

Adult↗
PubMed1998

Experience with teicoplanin in non-inpatient therapy in children with central line infections.

Indwelling intravenous catheters are an invaluable part of the curative therapy or terminal care of children with haematological malignancies. The increase in their use has been paralleled by an increase in Gram-positive infections, however. This article provides an overview of non-inpatient treatment of central line infections using teicoplanin. The main drivers for considering non-inpatient therapy were to increase the quality of the patient's life by reducing the amount of time spent in hospital, and to prolong the life of the catheter. A large proportion (95%) of the children in the unit described have indwelling catheters in situ, including Port-a-caths, Hickman catheters and Vascaths. The indications suitable for non-inpatient antibiotic therapy of line infections were those patients near the end of their chemotherapy courses, during terminal care, in non-neutropenic patients to complete an antibiotic course, and in patients with chronically neutropenic aplastic anaemia. Persistent line infections are not always eradicated but usually controlled. Care can take place in the home, in the general practitioner (GP) surgery or in the outpatient clinic. Care can be undertaken by nurses, older patients and parents. Follow-up procedures are in place to ensure safe, effective therapy.

Ambulatory Care↗
PubMed1997

Bone mineralization and turnover in children with congenital neutropenia, and its relationship to treatment with recombinant human granulocyte-colony stimulating factor.

Bone mineral content (BMC) of the radius was measured using single photon absorptiometry (SPA) in nine children with congenital neutropenia. Five had normal values. Two children with severe congenital neutropenia (SCN) had low BMC, and two boys with Schwachman syndrome had biochemistry suggestive of rickets.

Absorptiometry, Photon↗
PubMed1997

Potential salvage therapy for inadvertent intrathecal administration of vincristine.

Vincristine is an anti-neoplastic agent for intravenous use. Inadvertent intrathecal administration of vincristine tends to follow a predictable clinical sequence of a progressive ascending radiculomyeloencephalopathy, usually fatal in outcome. We report a case of a 10-year-old girl who suffered an inadvertent intrathecal vincristine administration. We have outlined the management strategy used and her consequent neurological progress. She has survived but with a significant neurological deficit. Her outcome is, however, less severe than in previous literature reports; this may in part be attributable to early aggressive neurological management. This case also serves to highlight the tragic consequences of human error when handling chemotherapeutic agents of this nature.

Antidotes↗
PubMed1996

Progressive glomerular toxicity of ifosfamide in children.

Glomerular toxicity following ifosfamide (IFO) is not as well recognized as renal tubular damage. Following a case of ifosfamide-induced renal failure with histological evidence of glomerular changes, we undertook a retrospective study of all IFO-treated children to assess the extent and severity of its glomerular toxicity and to identify possible predisposing factors. Thirty-seven children with a follow-up of 6 months or more from the end of chemotherapy were studied. They were a median of 10.8 years old (range 3.25-18.5), had received a median of 54 g/m2 (range 9-135) of IFO, and had a median follow-up of 29 months (range 6-68). The criteria to identify glomerular dysfunction were raised plasma creatinine (Pc) values on two occasions or a low glomerular filtration rate (GFR) measured by Tc-99-DTPA clearance. Detailed assessment was carried out to identify other nephrotoxic influences in these children. Subjects in whom glomerular dysfunction could be causally linked to IFO were compared with the rest of the group for a variety of predisposing factors. Of eight children with glomerular dysfunction, two had other nephrotoxic influences and were excluded from further analysis. In six (17.1%) children, glomerular dysfunction appeared to be causally linked to IFO. Their median GFR was 61.9 ml/min/1.73 m2(range 33-85) and Pc was 123 mumol/l (range 85-216). Five of the six had normal glomerular function at the end of therapy and the raised Pc values were first noted 19, 21, 26, 29, and 36 months later. Children with glomerular toxicity had a significantly longer median follow-up (41.5 vs. 19 months; P = 0.04) than the rest of the group, suggesting late onset of this problem. They were older at the time of the study and had received nearly twice the dose of IFO, though the differences in age and dose did not reach statistical significance. The earliest signs of renal toxicity were seen in the index case, who had had prior nephrectomy. All affected children had coexistent and preceding tubular toxicity. The inadequacies of tests commonly used to assess glomerular function and the possibility of underestimation of dysfunction are discussed. Glomerular dysfunction following IFO is poorly recognized and evidence from this study of its later onset and progressive nature is a cause for concern. The index case is described with histological findings.

Adolescent↗
PubMed1996

Effects of interleukin 6 administration on platelets and haemopoietic progenitor cells in peripheral blood.

Platelet numbers and circulating haemopoietic progenitor cells were examined in 12 patients with advanced malignancies who were receiving recombinant human interleukin-6 (rhIL-6) as part of an investigation of its thrombopoietic effects. Patients received recombinant glycosylated IL-6 by daily subcutaneous injection for 7 consecutive days in doses of 1, 3 or 10 micrograms/kg/day. Platelet numbers increased reaching a peak on days 12-15 with a mean on day 15 of 198.1% of pre-treatment values. This was accompanied by a significant fall in the mean platelet volume (mean decrease of 10.6%, P = 0.0044). No significant correlation was seen between the IL-6 dose and the change in platelet number. No significant differences were observed between pre- and post-treatment levels of circulating erythroid burst-forming units (E-BFU) and granulocyte macrophage colony-forming units (GM-CFU) but a small significant increase was seen in circulating primitive progenitor cells measured in a plastic-adherent (P delta) assay (P = 0.025). As positive controls, a group of patients treated with cyclophosphamide/G-CSF showed significant increases in GM-CFU (P = 0.018), E-BFU (P = 0.018) and P delta progenitors (P = 0.028). These data suggest that the thrombopoietic effects of IL-6 are mediated at a relatively late stage via effects on megakaryocyte differentiation, with a relatively small effect on circulating haemopoietic progenitors.

Adult↗
PubMed1996

Quantitative PCR of the immunoglobulin heavy chain gene using genomic DNA.

Techniques currently available enable the detection of clonal rearrangements of the immunoglobulin heavy chain gene using fluorescent PCR technology. It is possible to use this technique to analyse minimal residual disease throughout patient treatment: however, without the development of a quantitative assay, only the presence or absence of a clonal population can be determined. We describe here the development of a quantitative competitive PCR technique using genomic DNA which enables the rate of clearance of disease to be measured. In future, the ability to detect and also quantitate minimal residual disease may enhance the application of molecular investigations in the clinical management of patients.

DNA↗
PubMed1996

The dental management of children with sickle cell disease and beta-thalassaemia: a review.

This paper reviews two groups of haemoglobinopathies: sickle cell disorders and beta-thalassaemias. The medical aspects and dental management of children with these conditions are discussed. These conditions are rare in the white indigenous population of the UK but affect a sizeable proportion of the minority ethnic community. Dentists need to be aware of the medical implications for patients who have these disorders and should co-ordinate their dental care accordingly.

Anemia, Sickle Cell↗
PubMed1992

Use of flow cytochemistry via the H*1 in FAB identification of acute leukaemias.

Blood samples from 40 adult patients with untreated acute leukaemia were processed through the Technicon H*1 blood autoanalyser which gives a complete white cell differential count using flow cytochemistry and provides white cell cytograms as well. We examined the differences in the percentage differential counts and the white cell cytograms of various FAB types of acute leukaemia in an attempt to estimate the usefulness of this easily obtainable data for the identification of acute leukaemias. Differentiation of the 33 acute myeloid leukaemia (AML) cases from the 7 acute lymphoblastic leukaemia (ALL) cases was possible on the basis of lymphocyte percentage (AML mean 29.6 vs. ALL mean 67.1, p < 0.01), monocyte percentage (AML mean 12.5 vs. ALL mean 3.3, p < 0.001), mean peroxidase activity value (AML mean -12.6 vs. ALL mean -0.6, p < 0.01) and the absence of IG flag (circulating immature granulocytes) in ALL. Interestingly, the FAB subtypes of AML could be distinguished from each other on the basis of characteristic patterns of cell distribution in the peroxidase cytogram when the total white cell count was over 10 x 10(9)/l. Even with lower counts the differences were distinctive providing that circulating blasts were present.

Adult↗
PubMed1990

Ceftazidime monotherapy is as effective as ceftazidime combined with gentamicin in the treatment of febrile neutropenic patients.

To evaluate the efficacy of ceftazidime monotherapy in the empirical treatment of febrile neutropenic patients, a randomized trial was performed of ceftazidime (C) vs. ceftazidime and gentamicin (C + G) with the addition of teicoplanin (T) for those patients with a long intravenous line-associated infection. Success without modification at the end of treatment was seen in 32.7% (C), 28.3% (C + G), 52.4% (C + T) and 65.2% (C + G + T). Monotherapy with ceftazidime is as effective as when used in combination with an aminoglycoside in neutropenia.

Agranulocytosis↗
PubMed1988

The use of the H*1 in predicting marrow recovery following ablative chemotherapy in leukaemia and lymphoma.

Twenty-three cytopenic episodes in 18 patients undergoing ablative chemotherapy for the treatment of leukaemia or lymphoma were monitored from commencement of treatment until recovery, by automated differential counts using the Technicon H*1 Autoanalyser, with particular reference to abnormal white cell flags and large unstained cell (LUC) percentage. The blast flag was indicated in this recovery phase in 100% of patients and in 85% this preceded bone marrow recovery (defined as neutrophil count greater than 0.5 X 10(9)/l) by a mean of 10 days. On average the blast flag was indicated for 8 days in total. Bone marrow function continued to improve in all patients with no evidence of relapse. An increase in the LUC percentage on the differential count reached a maximum at 18 days, 6 days prior to marrow recovery. The ability to detect impending marrow recovery by means of the positive blast flag, may be of great value when patients have been cytopenic for many days.

Autoanalysis↗
PubMed1988

Accurate automated leucocyte differential counts despite profound leucopenia.

The differential white cell counts produced by the Technicon H*1 Autoanalyser in profoundly leucopenic specimens were compared with those carried out by manual differential counting by light microscopy of peripheral blood smears stained with May-Grünwald-Giemsa stain. The correlation achieved allowed the H*1 derived differential count to be reported with confidence.

Blood Cell Count↗