Search PubMed⌕ Search

Biomedical subjects

A Oakhill

Publications and source records attributed to A Oakhill.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cardioprotection by ICRF187 against high dose anthracycline toxicity in children with malignant disease.

OBJECTIVE: A pilot study to assess the efficacy of ICRF187 as a protective agent against the cardiotoxic effects of anthracycline drugs used to treat childhood malignancies. DESIGN: A study of cardiac function in children treated receiving ICRF187 ((s)-(+)-1,2 bis (3,5-dioxopiperazenyl) propane) in addition to anthracycline therapy compared with contemporary controls selected retrospectively on the basis of anthracycline dose matching. PATIENTS: Five children in whom recurrence of malignant disease was re-treated with chemotherapy containing anthracycline drugs and additional ICRF187 (supplied on a compassionate-use basis) (cumulative anthracycline doses 550-1650 mg/m2). Five more children with recurrence of malignant disease were re-treated to similar cumulative anthracycline doses (600-1150 mg/m2) without ICRF187. METHODS: Cardiac function was assessed clinically and echocardiographically throughout treatment. Clinical and echocardiographic state were compared before treatment and after completion of therapy within and between groups treated with and without ICRF187. RESULTS: Two patients treated without ICRF187 developed symptomatic congestive cardiac failure from which one died. Another developed considerable but as yet asymptomatic left ventricular dysfunction. No patient receiving additional ICRF187 developed cardiac failure or left ventricular dysfunction. There were no significant differences in cumulative anthracycline dose, dose increase, type of anthracycline used, survival rate, or length of survival between groups. Left ventricular shortening fraction fell by a mean of 1.0% in patients receiving ICRF187 and by a mean of 11% in the patients treated without it (p = 0.04). CONCLUSIONS: ICRF187 seems to have provided highly effective cardioprotection to this small group of children with end-stage malignancy. Severe cardiotoxicity was seen in a similar group treated with comparable anthracycline doses but without ICRF187.

Adolescent↗
PubMed1993

Cytomegalovirus pneumonitis and bone marrow transplantation: identification of a specific high risk group.

AIMS: To study the association between cytomegalovirus (CMV) excretion and interstitial pneumonitis in allogeneic bone marrow transplant (BMT) recipients, with reference to donor and recipient CMV antibody response. METHODS: The incidence of CMV excretion was prospectively studied in 62 allogeneic bone marrow transplantations performed on adults and children. All recipients received CMV seronegative blood products. Prophylaxis with high dose acyclovir and CMV immune globulin was given to high risk patients (donor or recipient, or both, CMV seropositive). RESULTS: CMV excretion was detected in eight of 26 (31%) high risk patients but in only one of 36 low risk patients (donor and recipient both CMV seronegative). Five of the eight (63%) excretors in the high risk category developed CMV, of whom four (80%) belonged to the seropositive recipient/seronegative donor group, and included the three CMV seropositive recipients whose CMV complement fixation antibody titres were 64 or greater before transplantation. CONCLUSIONS: These findings suggest that there is a subgroup of patients at especially high risk of developing CMV.

Adolescent↗
PubMed1993

Molecular evidence of minimal residual disease after treatment for leukaemia and lymphoma: an updated meeting report and review.

The very rapid development in the last few years of techniques based on use of the polymerase chain reaction (PCR) for characterizing molecular lesions in leukaemia and lymphoma now offers the opportunity for monitoring residual disease at a sensitivity of one malignant cell in 10(5) or 10(6) normal cells. Maximal specificity is presumably achieved when the DNA sequences amplified are truly leukaemia-specific, such as BCR/ABL in chronic myelogenous leukemia, RARA PML/RARA in t(15;17) acute myelogenous leukemia, DEK/CAN in t(6;9) AML, PBX1/E2A in t(1;19) acute lymphoblastic leukemia (ALL), or TAL-1 deletions in other T-ALLs. Comparable sensitivity may be achieved by using immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) gene rearrangements if a clonospecific probe can be generated. However, the presence of similar sequences in IgH genes from normal B lymphocytes may decrease the specificity. For clinical purposes the crucial issues are the following. Can PCR techniques be used for confirmation of diagnosis and evaluation of extent of disease? Can PCR data obtained in remission provide information about the probability of cure or of relapse? Can techniques be developed to quantitate the PCR product and thereby increase its predictive value? These and other issues were addressed at the 4th Workshop of the Molecular Biology/BMT Study Group that took place in Bristol UK on 9-10 May 1992.

Humans↗
PubMed1993

Immune reconstitution after BMT in children.

Serial assessment of peripheral blood T and B cell recovery and serum immunoglobulins was performed in 19 children for the first year following BMT and compared with normal values established from healthy children. Immunophenotypic analysis on bone marrow was performed in selected cases by Southern blotting of the immunoglobulin heavy chain (IgH) gene. We found no significant differences between T cell-replete or depleted allogeneic bone marrow transplants. Lymphocyte numbers were low until 9 months post-BMT. T cell numbers (CD2, CD3, CD5) were also low until 12 months but B cell numbers (CD19) became normal at 3 months. Both CD4+ and CD8+ T cell subsets were low post-BMT with depression of CD4+ greater and more prolonged than that of CD8+. No overshoot of CD8+ was seen. The principal effect of GVHD or its treatment was further depression of CD4+ cells but with no increase in CD8+; recovery of B cells was also delayed. Recovery of IgG was slow with only six of 11 children reaching an age-adjusted normal level by 1 year, whereas there was more rapid recovery of IgM and IgA. Several children had an increase in lymphocytes of immature appearance in their bone marrow at varying times post-BMT with increased cells of phenotype CD19+, CD10+, HLA-DR+ and TdT+. In each case Southern blotting showed a germline pattern of the IgH indicating a polyclonal early B cell regenerative population.

Adolescent↗
PubMed1993

Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction.

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.

Bone Marrow Transplantation↗
PubMed1992

Acute monoblastic leukemia of infancy in Klinefelter's syndrome.

A 7-month-old infant with Klinefelter's syndrome was diagnosed as having acute monoblastic leukemia (AMoL). Chromosome studies of bone marrow at diagnosis showed the karyotype 46,XXY,-Y,t(10;11)(p13;q14). This is the first report of M5A leukemia associated with Klinefelter's syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Causes of death in a paediatric oncology unit.

The records of 101 patients (64 males and 37 females) registered at Bristol Children's Hospital who died between January 1986 and December 1989 were reviewed to determine the cause of death. Nineteen patients (19%) died without obtaining remission and 6 (6%) in first remission. Seventy-six (75%) died after relapse; three during re-induction and two in second remission. The causes of death were active disease in 85 patients (84%), active disease and infection (4%), active disease and other factors (4%), infection only (3%), toxic cardiomyopathy (2%), graft versus host disease (2%), and second malignancy (1%).

Bone Neoplasms↗
PubMed1992

An assessment of sputum induction as an aid to diagnosis of respiratory infections in the immunocompromised child.

Sputum induction using nebulised hypertonic saline was performed in two groups of immunocompromised children, one group with symptoms of respiratory infection and one group without. The asymptomatic group were bone marrow transplant (BMT) recipients, all seropositive for cytomegalovirus infection (CMV). Organisms were identified in three of 14 induced sputum specimens obtained from the symptomatic group (CMV N = 1, Haemophilus influenzae N = 2), but in none of 12 specimens from the asymptomatic group. Adverse effects encountered were minor. Four symptomatic patients with negative induced sputum samples underwent bronchoalveolar lavage, and no further organisms were identified. Sputum induction can be a useful adjunct to the diagnosis of respiratory pathogens in this group of patients.

Adolescent↗
PubMed1992

Third complementarity determining region (CDR III) sequence analysis in childhood B-lineage acute lymphoblastic leukaemia: implications for the design of oligonucleotide probes for use in monitoring minimal residual disease.

The genetic sequence of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain (IgH) gene was analysed in 55 rearranged alleles from 36 children presenting with B-lineage acute lymphoblastic leukaemia (ALL). This confirmed the unique nature of these rearrangements. However, contrary to the hypothesis that the CDR III is produced by a random process of rearrangement, biased utilisation of diversity (D) segments and of joining (J) regions 4, 5 and 6 was demonstrated. Moreover, preferred sequence boundaries were seen in J regions 1 to 5 and were suggested at the 3'-end of certain D regions, notably D21/9 and DK1. Similar patterns of rearrangement have been noted in normal B-lymphocyte clones. Together with relatively limited N nucleotide addition, these factors may restrict the potential sequence variability at the D-N-J junction. The occurrence of clonal progression by secondary gene rearrangements, such as V-V replacement, favours the use of this site when designing clone-specific oligonucleotide probes for use in monitoring minimal residual disease (MRD). In cases where biased features of D-J rearrangement are shared by both the leukaemic and normal B-lymphocyte clones this could reduce the sensitivity of these probes in detecting low levels of residual disease.

Base Sequence↗
PubMed1992

Detection of clonality in childhood B-lineage acute lymphoblastic leukaemia by the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to study clonality in a group of children with B-lineage acute lymphoblastic leukaemia (ALL). Rearrangement of the immunoglobulin heavy chain gene (IgH) results in a hypervariable sequence known as the complementarity determining region III. This can be amplified by the PCR using one pair of consensus primers. The PCR product is highly clone-specific in both size and sequence. Successful amplification was achieved in 50 of 62 cases of B-lineage ALL studied (81%). Both DNA and RNA gave almost identical results. In contrast amplification was only achieved in 2 of 42 control cases (non-B-lineage leukaemias, normal and reactive marrows); these were both cases of T-ALL with IgH rearrangement on Southern blotting. The main advantages of this technique over Southern blot assessment of clonality are the short time to result and requirement for much less DNA allowing study of small samples eg cerebrospinal fluid and testicular biopsies. It is also generally more sensitive for the detection of a malignant clone in a polyclonal marrow cell population and forms the basis of techniques to study minimal residual disease (MRD).

Adolescent↗
PubMed1991

Gingival swelling as a manifestation of aplastic anemia.

Gingivitis in the preschool child is uncommon and is usually associated with underlying systemic disease such as leukemias, neutropenias, and other immunologic defects. This report describes gingival hyperplasia in a preschool child with aplastic anemia and highlights the need to exclude systemic disease in children with periodontal disease.

Anemia, Aplastic↗
PubMed1991

Influenza A and the virus associated haemophagocytic syndrome: cluster of three cases in children with acute leukaemia.

At the height of the United Kingdom influenza A epidemic in December 1989, three children receiving treatment for non-T cell acute leukaemia developed pancytopenia with concomitant influenza A infection. Bone marrow histology showed prominent marrow erythrophagocytosis by morphologically mature histiocytes, consistent with the picture of virus associated haemophagocytic syndrome (VAHS). In two cases there was an initial spontaneous recovery, though recurrence of VAHS developed in one case in association with a different viral infection (cytomegalovirus) following autologous bone marrow transplantation. The third child died from cardiorespiratory failure secondary to infection with influenza A and Klebsiella pneumoniae sepsis. It is suggested that influenza A should be added to the list of infective causative agents.

Child↗
PubMed1991

Graft-versus-host disease in children receiving HLA-identical allogeneic bone marrow transplants with a low adjusted T lymphocyte dose.

Fourteen children with high risk leukaemia received allogeneic bone marrow transplants from HLA-identical MLC-compatible sibling donors. All bone marrows were T cell depleted and a T cell addback was prepared from the donor's peripheral blood so that the mean total number of CD3+ cells given was 2.6 (1.0-4.1) x 10(5)/kg recipient body weight. This was administered as a short infusion prior to the bone marrow. The children were conditioned with 1440 cGy fractionated total body irradiation and cyclophosphamide 120 mg/kg and were not given cyclosporin A or methotrexate. All patients engrafted and none showed late graft rejection. Acute graft-versus-host disease (GVHD) developed in nine of 14 children and required treatment with steroids. Two children with grade IV GVHD and one with grade I acute GVHD who subsequently developed severe chronic GVHD died. There have been two relapses (both fatal) and one death from cytomegalovirus pneumonitis. Survival is currently 57% (8/14) with a mean follow-up of 548 days (range 384-810). A high incidence of GVHD which was fatal in three patients can occur despite infusion of low T cell numbers in the absence of post-graft immunosuppression.

Adolescent↗
PubMed1991

Effective emetic control during conditioning of children for bone marrow transplantation using ondansetron, a 5-HT3 antagonist.

Preparation for bone marrow transplantation (BMT) uses the extremely emetogenic combination of chemotherapy and total body irradiation (TBI). Ondansetron is a selective 5-HT3 antagonist and has clear anti-emetic capabilities. The efficacy of the drug was assessed in 15 children (aged 2-17 years) who received high dose cyclophosphamide (on days -6 and -5) and TBI (days -3 to 0 inclusive). During days -6 to -4 when the emetic effect of cyclophosphamide would be most pronounced, 12 of the 15 patients (80%) had fewer than five emetic episodes during their worst 24-h period, 11 (73%) had fewer than three vomits whilst nine (60%) experienced no vomiting or retching. Eleven patients progressed to TBI and 10 (91%) had fewer than five emetic events in the worst 24-h period (days -3 to +2), six (55%) had no vomiting at all. Of 100 evaluable 'patient-days' 83 (83%) were without any vomiting or retching and a further 10 'patient-days' had only one or two emetic episodes. There were no significant side-effects noted and in particular no extrapyramidal reactions. Headaches and constipation, which have been seen in adult studies, were not reported by patient or parent on any of the study days and transient elevation of liver enzymes were noted in only two patients. Ondansetron has a major role in preparing patients for BMT.

Adolescent↗