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Biomedical subjects

S E Kinsey

Publications and source records attributed to S E Kinsey.

At least 19 recordsLinked to original sources
PubMed2006

The investigation and management of chronic neutropenia in children.

Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered.

Child↗
PubMed2005

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial.

Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0.0007). Event-free survival was significantly improved with dexamethasone (84.2% vs. 75.6% at 5 years; P = 0.01), with no evidence of differing effects in any subgroup of patients. The use of 6.5 mg/m(2) dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.

Adolescent↗
PubMed2005

Successful recovery of aplastic anemia following orthotopic liver transplantation for non-A-E acute liver failure.

This report describes a teenager who developed aplastic anemia (AA) because of non-A-E acute liver failure (ALF) requiring orthotopic liver transplantation (OLT). His AA did not recover spontaneously and he required treatment with ATG 9 months post-OLT. Bone marrow recovery occurred 4 months after immunotherapy and coincided with further intensification of immunusuppression required to treat early chronic rejection of the liver graft. Three years post-OLT he remains well with good bone marrow and liver function. Intensification of immunosuppression can lead to successful resolution of AA associated with non-A-E ALF.

Adolescent↗
PubMed2004

Diagnosing childhood cancer in primary care--a realistic expectation?

The burden of childhood cancer for Primary Care Trusts (PCTs) is unknown. PCTs in Yorkshire are representative of England and Wales and show little heterogeneity in the incidence rates of childhood cancer. Each PCT will expect three to five newly diagnosed children per year. A single GP is likely to see an incident case once every 20 years.

Adolescent↗
PubMed2004

Geographic mobility following cancer treatment in Yorkshire, UK.

Long term cure and maximising reintegration into society are major goals of childhood cancer treatment. Whether reintegration had occurred was assessed using geographic mobility as an objective proxy. Age, sex, and socioeconomic status were identified as being independently associated with mobility whereas diagnosis and relapse were not.

Adolescent↗
PubMed2003

Non-Hodgkin lymphoma presenting with obstructive jaundice.

BACKGROUND: Obstructive jaundice is a rare presenting feature of non-Hodgkin lymphoma (NHL). Lymphomatous masses in the peripancreatic and hepatic hilar regions are potentially difficult to diagnose. METHODS: A retrospective analysis was undertaken of patients presenting with obstructive jaundice secondary to NHL at a tertiary care hepatobiliary unit. RESULTS: Over a 7-year period, six adults and three children with NHL were managed. The site of the lymphomatous mass was at the hepatic hilum in six patients and the peripancreatic area in three. Diagnostic procedures included a laparotomy and biopsy in four patients, hepatic trisectionectomy in two, percutaneous biopsy in two and lymph node biopsy in one patient. Percutaneous biopsy confirmed the diagnosis in both the patients in whom it was attempted. One patient died following liver resection. Chemotherapy was the mainstay of treatment and achieved complete remission in four patients, partial remission in three and no response in one patient. Two patients subsequently required operation for a benign biliary stricture after achieving complete remission. CONCLUSION: NHL must be considered in the differential diagnosis of obstructive jaundice in adults and children. Attempts must be made to diagnose the condition using non-operative techniques. Chemotherapy is the mainstay of treatment. Late benign strictures of the bile duct requiring operation may develop.

Adolescent↗
PubMed2003

Patterns of childhood cancer by ethnic group in Bradford, UK 1974-1997.

The highly urbanised northern English city of Bradford contains a diverse population from different ethnic backgrounds, including a high proportion of south Asians. We aimed to identify the effect of ethnic group on the incidence and temporal trends of childhood cancer in Bradford. Children (0-14 years) from the district of Bradford, who were diagnosed with a malignancy between 1974 and 1997, were selected from a population-based register. Each child was classified as south Asian (Indian, Pakistani and Bangladeshi), or not, based on their full name using 2 computer algorithms and individual inspection. Mid-year population estimates were used to calculate incidence rates and differences were assessed using Poisson regression. The study included 318 children, of whom 81 (25%) were south Asian. The incidence of all cancers in south Asian children (14.9 per 100,000 person years, 95% CI 11.6-18.2) was higher than non-south Asian children (12.0, 10.5-13.5) although not significantly so (P=0.14). Comparisons by diagnostic subgroup showed no major differences apart from significantly higher rates of acute myeloid leukaemia (AML) in south Asian children (1.9 versus 0.7, P=0.02). The age-specific incidence peaks of all childhood cancers and leukaemias were present in south Asian children aged 5-9 years compared with 0-4 years olds in the non-south Asian population. Non-significant increases of 1.4 and 1.5% in the average annual incidence of all cancers were seen for south Asians and non-south Asians respectively, with a significant rise for non-south Asians with leukaemia of 3.0% (P=0.04). Our timely study shows patterns of occurrence of childhood cancer that differ with respect to ethnic group. Differences are particularly apparent in the excess of AML and incidence peak in 5-9 year olds in south Asian children.

Adolescent↗
PubMed2002

Population mixing, childhood leukaemia, CNS tumours and other childhood cancers in Yorkshire.

We tested the hypothesis that variation in population mixing attributable to the diversity of migrants moving to an area is associated with the incidence of childhood leukaemia and other childhood cancers. An ecological analysis was performed on 954 children (<15 years) diagnosed with a malignancy between 1986 and 1996 in 532 electoral wards in Yorkshire, UK. Incidence rate ratios (IRR) were calculated for all childhood leukaemias (n=325), acute lymphoblastic leukaemia (ALL) (n=248), central nervous system (CNS) tumours (n=236) and other solid tumours (n=393) Incidence of all childhood leukaemias was significantly lower in areas of high (top decile) population mixing (IRR 0.72, 95% Confidence Interval (CI) 0.54-0.97) and higher in areas of low (bottom decile) population mixing (IRR 1.56, 95% CI 0.73-3.34), but similar patterns of incidence were not observed for central nervous system or other solid tumours. Population mixing may be a proxy for the range of infections circulating in a community and these results are consistent with the hypothesis that greater exposure to infections reduces the risk of developing childhood leukaemia by conferring efficient modulation of the immune system.

Adolescent↗
PubMed2001

Incidence of childhood acute lymphoblastic leukaemia in Yorkshire, UK.

Between 1980 and 1998, in the north-west of England, a significant rise in childhood acute lymphoblastic leukaemia was caused by an increase in the precursor B-cell form of this disease. We analysed data on children who were diagnosed with leukaemia in Yorkshire, UK, between 1974 and 1997. The incidence of acute lymphoblastic leukaemia remained stable, although a non-significant yearly increase of 2.4% was noted for the precursor B-cell form of this disease from 1980 onwards. The precursor B-cell form accounted for 80% of all acute lymphoblastic leukaemia. Our data are not consistent with increasing incidence for precursor B-cell acute lymphoblastic leukaemia, although numbers of children with acute myeloid leukaemia are rising.

Burkitt Lymphoma↗
PubMed2001

Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma.

BACKGROUND: Despite treatment with high-dose myeloblative chemotherapy and peripheral blood stem cell (PBSC) rescue, a high proportion of children with neuroblastoma relapse and die. Re-infusion of PBSC contaminated with tumour at the time of autologous transplantation may play a significant role in this relapse. In this study the frequency of tumour contamination in PB from children with neuroblastoma has been investigated. PROCEDURE: Minimal residual disease was measured using RT-PCR for tyrosine hydroxylase (TH) mRNA in PBSCs from patients with advanced neuroblastoma. PBSCs from 18 patients in complete clinical remission were studied. RESULTS: Studies in other cancers have suggested minimal contamination of PBSCs with tumour cells; TH mRNA was detected by RT-PCR in 50% (9/18) of PBSC harvests. Seventy-seven percent (7/9) of patients with TH mRNA in PBSC died of disease compared to 44% (4/9) who were TH mRNA-negative. CONCLUSIONS: Therefore, the presence of TH mRNA in PBSCs appeared to be associated with an unfavourable outcome, although this was not statistically significant. In summary, RT-PCR for TH mRNA is a sensitive method for the identification of tumour cells in PBSC harvest. The presence of TH mRNA in PBSC harvest may reflect disease status and be associated with an unfavourable outcome, although long-term clinical outcome studies in a larger patient cohort are required.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Remission of severe, intractable autoimmune haemolytic anaemia following matched unrelated donor transplantation.

Immune-mediated haemolytic anaemia presenting post allogeneic bone marrow transplantation is often alloimmune in origin due to ABO or minor red cell incompatibilities. Autoimmune haemolytic anaemia is also recognised, is frequently difficult to treat and overall prognosis is often poor, usually from associated problems. Here, we present a case report of autoimmune haemolysis presenting in an 8-year-old boy 6 months post allogeneic bone marrow transplant requiring 4 years of immunosuppressive therapy before remission of haemolysis. This case report highlights the fact that it is possible for haemolysis to resolve post transplant even after years of immunosuppressive therapy.

Adrenal Cortex Hormones↗
PubMed2000

Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.

Granulocyte colony-stimulating factor (G-CSF) has had a major impact on management of "severe chronic neutropenia," a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital neutropenia, treated with G-CSF from 1987 to present. Treatment and patient demographic data were analyzed. The 352 congenital patients were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of malignant transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic neutropenia developed MDS/AML. Transformation was associated with acquired marrow cytogenetic clonal changes: 18 patients developed a partial or complete loss of chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML development was less than 2%. No significant relationships between age at onset of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P >.15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other patient demographics, we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML was not seen in cyclic or idiopathic neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF therapy may allow time for the expression of the leukemic predisposition that characterizes the natural history of these disorders. However, other factors related to G-CSF may also be operative in the setting of congenital neutropenia. (Blood. 2000;96:429-436)

Adolescent↗
PubMed2000

A herpesvirus saimiri-based gene therapy vector with potential for use in cancer immunotherapy.

The herpesvirus saimiri (HVS) genome has the capacity to incorporate large amounts of heterologous DNA and can be maintained episomally in many different human cell types. To evaluate the efficacy of HVS-mediated gene transfer into human hemopoietic cells, we investigated the ability of an HVS-based construct, carrying the enhanced green fluorescent protein (EGFP) and neomycin resistance genes, to transduce a variety of human hemopoietic cell lines and primary CD34+ cells. As measured by flow cytometry, the numbers of EGFP+ cells at 2 days postinfection differed between various cell types ranging, from 1.3% for KG1 cells to 56.8% for THP-1 cells. In addition, the expression of EGFP in Jurkat cells was retained at >95% per round of cell division over a period of 6 weeks (comparable with Epstein-Barr virus-derived gene therapy systems). Although the virus was not specifically disabled, no lytic viral mRNAs could be detected in transduced Jurkat cells, and infectious virus could not be detected by sensitive virus recovery assay. We also describe a simple centrifugation method that increases the efficiency of transduction by >100% in some cases and may be generally applicable to other herpesvirus-based vectors for ex vivo gene delivery. Using this technique, we were able to demonstrate a tropism for CD34+/CD14+ cells, transducing 30% of the population. These cells are known to give rise to dendritic cells (the most potent of the antigen-presenting cells), suggesting that the vector could be used to deliver DNA sequences encoding tumor antigens for cancer immunotherapy.

Antigens, CD34↗
PubMed2000

Herpesvirus saimiri-based gene delivery vectors maintain heterologous expression throughout mouse embryonic stem cell differentiation in vitro.

In order to achieve a high efficiency of gene delivery into rare cell types like stem cells the use of viral vectors is presently without alternative. An ideal stem cell gene therapy vector would be able to infect primitive progenitor cells and sustain or activate gene expression in differentiated progeny. However, many viral vectors are inactivated when introduced in developing systems where cell differentiation occurs. To this end, we have developed a mouse in vitro model for testing herpesvirus saimiri (HVS)-based gene therapy vectors. We demonstrate here for the first time that HVS is able to infect totipotent mouse embryonic stem (ES) cells with high efficiency. We have transduced ES cells with a recombinant virus carrying the enhanced green fluorescent protein (EGFP) gene and the neomycin resistance gene (NeoR) driven by a CMV promoter and the SV40 promoter, respectively. ES cells maintain the viral episomal genome and can be terminally differentiated into mature haematopoietic cells. Moreover, heterologous gene expression is maintained throughout in vitro differentiation. Besides its obvious use in gene therapy, this unique expression system has wide ranging applications in studies aimed at understanding gene function and expression in cell differentiation and development.

Animals↗
PubMed2000

Stable marker gene transfer into human bone marrow stromal cells and their progenitors using novel herpesvirus saimiri-based vectors.

We have evaluated the ability of new herpesvirus saimiri (HVS)-based vectors to deliver a marker gene green fluorescent protein (GFP) into human bone marrow (BM) stromal cells and their progenitors. Stromal cells expanded from adherent layers of long-term BM cultures (LTC) were susceptible to HVS-based infection in a dose-dependent manner, and the efficiency of 94.8 +/- 2.0% was achieved using single exposure with HVS/EGFP vector at multiplicity of infection (moi) of approximately 50. Colony-forming unit-fibroblast (CFU-F) assay established the ability of HVS-based vectors to infect progenitors for bone marrow stroma fibroblasts and transfer the marker gene over multiple cell divisions in the absence of selective pressure. HVS was not toxic for stromal cells and progenitors and no viral replication was detected upon growth of modified stroma. On the basis these data, we believe that HVS-based constructs can offer a new opportunity for selective gene delivery into bone marrow stromal cells and progenitors. The ability of HVS to infect nondividing cells can be considered advantageous in the development of both ex vivo and in vivo strategies.

Bone Marrow Cells↗
PubMed1999

Survival from childhood cancer in Yorkshire, U.K.: effect of ethnicity and socio-economic status.

The effect of ethnicity and socio-economic status on the survival of a population-based cohort of 1979 children diagnosed with cancer between 1974 and 1995 was investigated. Ethnicity was assigned by computer algorithms and visual inspection as south Asian (or not) for each child, based on their full name. Socio-economic status was measured using the Carstairs index, based on census areas of case residence at diagnosis. 15 children (0.8%) were lost to follow-up. Log-rank tests showed survival from all cancers did not differ between south Asians and other children and no increased risk was observed for south Asians in any diagnostic category, although numbers were small. Increasing levels of deprivation were associated with significant trends of poorer survival from all cancers, leukaemias and brain tumours. Risk of death was typically higher for children from the most deprived areas although differences were not statistically significant after accounting for other factors including ethnicity. Taking all children with malignant disease together, neither ethnicity nor socio-economic status appear to influence survival after taking other factors into consideration.

Adolescent↗