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Biomedical subjects

A Oakhill

Publications and source records attributed to A Oakhill.

At least 73 records · Page 4Linked to original sources
PubMed1995

Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology.

OBJECTIVES: To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. DESIGN: Cross sectional echocardiographic study of LV function. SETTING: Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. PATIENTS: 226 of 236 patients surviving between 6.5 months and 17 (median 5.3) years from initial anthracycline treatment for childhood malignancy attended for clinical and echocardiographic examination. Cumulative anthracycline doses were between 50 and 750 (median 300) mg/m2. 22 patients had also received cardiac irradiation. METHODS: Detailed assessment of transmitral diastolic pulsed wave Doppler flow patterns along with LV dimensions and systolic function measured by M mode echocardiography. MAIN OUTCOME MEASURES: Peak early (E) and atrial (A) phase filling velocities and EA ratio, time and acceleration and deceleration to and from peak E velocity, velocity integrals and ratio, isovolumic relaxation time (IVRT), and heart rate were measured. Results were examined in relation to LV cavity and posterior wall dimensions and shortening fraction (SF), and compared with paired control data matched for body surface area. RESULTS: Eleven (5%) patients had abnormal effort tolerance. Fifty one (23%) had SF < 30% and SF was inversely correlated with cumulative dose and time from treatment. The relative risk of symptomatic cardiac failure was greatly increased by prior irradiation; > 60% of irradiated patients who received > 400 mg/m2 of anthracycline were symptomatic. Early diastolic filling was relatively normal or enhanced at low anthracycline doses or when SF was preserved, with a shorter IVRT and increased atrial phase filling. Early filling was reduced at higher doses or with reduced SF, with longer IVRT and a further increase in atrial phase filling. A more "restrictive" pattern of diastolic filling (with high E and low A velocities) was seen in some patients, particularly after cardiac irradiation. CONCLUSIONS: Significant abnormalities of diastolic function are associated with anthracycline induced cardiac damage. These are not linearly related to anthracycline dose but appear to reflect the underlying myocardial pathophysiology associated with anthracycline toxicity, which is not demonstrated by the standard M mode echocardiogram. Although the overall clinical significance of such diastolic dysfunction is uncertain, some individual abnormalities may have significant management and therapeutic implications.

Adolescent↗
PubMed1995

Changes in cytomorphology of childhood lymphoblastic leukaemia at the time of disease relapse. Childhood Leukaemia Working Party of the United Kingdom Medical Research Council.

AIMS: Children in a United Kingdom national trial for relapsed non-B lymphoblastic leukaemia (ALL) had their diagnostic and relapse marrow cytomorphology compared to see what changes occur during the evolution of the disease. METHODS: Each relapse slide was assessed blindly for French American British (FAB) type and other morphological features by a panel of three independent microscopists without reference to each other or any diagnostic material. Diagnostic slides had been assessed by the same panel on an earlier occasion. RESULTS: A total of 134 consecutive children was studied. Six (5%) were classified as FAB type L2 at diagnosis, compared with 18 (13%) at relapse (a difference of 9%). Twenty two (16%) changed their FAB type, 17 (13%) from L1 to L2 and five (4%) from L2 to L1. The FAB score fell at relapse in 34 children and rose in 14, a difference of 14%. Cell size was the commonest feature to change (increasing in 22 and diminishing in nine) followed by prominent nucleoli (appearing in 21 and disappearing in six). Forty four (33%) children had vacuolated blasts at diagnosis, compared with 48 (36%) at relapse. Twenty five changed their vacuole score substantially, 14 gaining > 10% and 11 falling < 10%. CONCLUSIONS: These findings reflect the variability of lymphoblast cytomorphology, but also show a trend for cells to have more prominent nucleoli and greater size at relapse. Factors controlling these features of the FAB type are unknown, but they may simply be related to the growth fraction of a particular disease and not to any lineage specific biological feature.

Adolescent↗
PubMed1995

Fatal adenovirus 32 infection in a bone marrow transplant recipient.

A case of disseminated adenovirus type 32 infection causing severe hepatitis, gastrointestinal ulceration and also with respiratory involvement is reported in a bone marrow transplant recipient. Typical viral inclusions were seen in the postmortem histological sections and adenovirus infection was confirmed using in situ hybridisation and isolation of adenovirus type 32 from separate organs at necropsy. This is the first case in which adenovirus 32 was the cause of fatal disseminated disease in a bone marrow transplant recipient.

Adenovirus Infections, Human↗
PubMed1995

Models of care for children dying of malignant disease.

Two-thirds of children with cancer are now cured of their disease. For the majority of the remainder there is a period of terminal care. The emphasis of care at this stage is on the quality of life for both child and family. Most families prefer that their child should be cared for at home, with professional support from those known to them. This paper looks at various approaches to terminal care in children and describes the model of care for such children in the south west of the United Kingdom. From this information, key elements of an effective service are identified.

Child↗
PubMed1995

Congenital astroblastoma: an immunohistochemical study. Case report.

Astroblastoma is a rare type of glial tumor, usually occurring in older children and young adults. It has a distinctive histological appearance that is characterized by a radiating arrangement of tumor cells that form perivascular pseudorosettes. The authors report only the second case of astroblastoma presenting in congenital form. Following subtotal tumor resection, the infant received 10 courses of chemotherapy consisting of vincristine, etoposide, and carboplatinum. Evidence is presented for a tumor response to chemotherapy, a previously unreported observation. The child is alive 2.5 years after diagnosis with satisfactory functional status. Immunohistological and ultrastructural features of this tumor are presented. The discussion focuses on the biology, natural history, and management of this unusual neoplasm.

Astrocytoma↗
PubMed1994

Decline in incidence of medulloblastoma in children.

BACKGROUND: Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. METHODS: A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. RESULTS: In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. CONCLUSIONS: In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma.

Adolescent↗
PubMed1994

A polymerase chain reaction study of the stability of Ig heavy-chain and T-cell receptor delta gene rearrangements between presentation and relapse of childhood B-lineage acute lymphoblastic leukemia.

Ig heavy-chain (IgH) and partial V delta 2-D delta 3 T-cell receptor (TCR) gene rearrangements were investigated, by polymerase chain reaction (PCR) amplification and sequence analysis, in 52 patients at presentation and first relapse and in 14 at both first and second relapse of B-lineage acute lymphoblastic leukemia. In combination, these techniques amplified one or more clonal markers at presentation in 90% of patients (IgH-PCR, 75%; V delta 2-D delta 3-PCR, 46%; both, 33%). Changes in the pattern of amplification between presentation and first relapse were seen in 31% of patients positive by IgH-PCR at presentation and in 25% of those positive by TCR delta-PCR. Only 3 patients showed complete change in their rearrangements, which is suggestive of relapse with a new clone. Furthermore, despite the high reported rates of oligoclonality and clonal evolution at the IgH locus, the results presented show that false-negative minimal residual disease (MRD) detection can be avoided by designing D-N-J probes to all presentation rearrangements. Using a PCR approach for both gene markers, false-negative testing because of clonal evolution would have only occurred in 3 (8%) of the IgH-positive patients, in contrast to 5 (21%) of V delta 2-D delta 3-positive patients. Combining these two systems increases the proportion of patients open to study to 90%, allows comparative studies of the sensitive of the two methods, and reduces the rate of false-negative assessment of MRD caused by clonal evolution to less than 10%. We conclude that large prospective PCR studies of MRD detection should examine gene rearrangements at multiple loci to maximize their applicability and to minimize false-negative relapse prediction.

Adolescent↗
PubMed1994

Childhood malignancies in the south-west region of England, 1976-1985.

The incidence and pattern of childhood cancer in the South-West Region of the United Kingdom was studied in the period 1976-1985 to see if there was any unevenness in distribution. This region consists of five counties with considerable variation in radon exposure and urbanisation. Cases were identified from multiple sources and the basis of the diagnosis reviewed. Internationally accepted diagnostic categories were used. Six hundred seventy-eight cases were found, giving an age standardised incidence rate of 114.2 per million childhood years. The incidence of different cancers by sex was strikingly similar to the Manchester Children's Tumour Registry, from a noncontiguous region, with three exceptions. In the South-West, there was a higher rate of soft tissue sarcoma in boys (P = 0.01) and lower rates of sympathetic nervous system and germ-cell tumours in girls (P = 0.01 and P = 0.04, respectively). There was no significant variation in cancer incidence among the five counties or with time. The incidence rate in counties of high radon exposure was not higher than with low radon exposure. The overall incidence in counties with urban districts was not significantly increased compared to those without, although there was a nonsignificant trend towards a higher incidence of leukaemia (P = 0.08). The incidence and type of childhood cancer are similar to those in a noncontiguous region. Geographical and temporal incidence are remarkably stable. Local environmental variation may not play a major role in the causality of childhood cancer.

Adolescent↗
PubMed1994

A comparison of four ultraviolet sources to alter graft-versus-host responses.

Graft-versus-host disease (GVHD) is a major contributor to the morbidity and mortality associated with allogeneic bone marrow transplantation. Direct ultraviolet B (UVB) irradiation of bone marrow and spleen cell allografts in mice using broadband lamps is known to abolish alloreactive responses which would normally cause GVHD. Using a histoincompatible murine model, we have extended these observations by comparing the physical spectrum of four UV sources (the Philips TUV8W, TL12 and TL01, and the Spectronics XX15B) with in vitro assessment of bone marrow progenitor cell damage and suppression of lymphocyte proliferation and in vivo comparison of the effect on GVHD of the TL12 and XX15B and on the rate of engraftment with the TL12. At doses of uv found to abolish lymphocyte proliferation (2.5, 7, 12 and 1000 J m(-2) with the TUV8W, XX15B, TL12 and TL01 lamps) colony-forming unit granulocyte-macrophage (CFU-GM) proliferation was reduced to 81%, 71%, 79% and 62%, respectively. At an optimal dose found to suppress GVHD (100 J m(-2) integrated radiant energy from 200-320 nm for the TL12 and XX15B) CFU-GM proliferation showed a reduction of 98% with the XX15B and 86% with the TL12. At this radiant energy with the TL12, the rate of bone marrow engraftment was impaired with 72% marrow cellularity at 2 weeks, decreasing to 48% after 200 J m(-2). Our results with this model demonstrate that broadband UVB irradiation of bone marrow permits transplantation across a major histocompatibility barrier. Furthermore we have provided in vitro evidence that narrowband UVB or UVC might potentially be applied to this model.

Animals↗
PubMed1994

PCR assessment of bone marrow status in 'isolated' extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia.

Approximately one-third of first relapses of childhood ALL occur at an extramedullary site without morphological evidence of bone marrow disease. However, the high incidence of subsequent medullary relapse in these cases strongly suggests that leukaemia is present at submicroscopic levels at the time of 'isolated' relapse. PCR analysis of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements now allows detection of leukaemia at levels as low as 0.001%. We have therefore used this technique to reassess bone marrow status at morphologically isolated relapse in 13 children with B-lineage ALL (11 with off-treatment relapses, two on treatment). In 12 of these 13 patients marrow disease was detectable by PCR at the time of this relapse--in all cases at levels below the threshold of light microscopy. Where relapse occurred off-therapy this indicated re-emergence of disease. since MRD has never been detected by PCR at this stage in patients remaining in long-term remission. In both patients who relapsed on-therapy the level of MRD at the time of relapse represented an increase on that seen in their previous marrow sample. We conclude that re-emerging bone marrow disease can be detected in most cases of 'isolated' relapse when investigated by this highly sensitive technique. Our findings at a molecular level confirm a long-held clinical suspicion and indicate that full systemic re-induction as well as local therapy is obligatory for these children.

Adolescent↗
PubMed1994

Genetic analysis in a female manifesting haemophilia B.

A 5 year old female child presented with a psoas haematoma as the first manifestation of haemophilia B. Molecular genetic studies were performed to investigate the inheritance of the disorder and the mechanisms by which females may express the haemophilia B phenotype are discussed.

Child, Preschool↗
PubMed1993

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The significance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia.

In acute lymphoblastic leukaemia (ALL), minimal residual disease (MRD) can be defined as disease occurring at a subclinical level and beyond detection by conventional methods of assessment. Application of the polymerase chain reaction (PCR) to the hypervariable segment of the immunoglobulin heavy chain (IgH) gene, allows detection of MRD at a level of one leukaemic cell in 10(4)-10(5) normal marrow cells. We have performed a retrospective study using this technique in the assessment of children with precursor B-cell ALL in whom the clinical outcome is known. In the early treatment period MRD is commonly detected in children who remain in complete remission on subsequent follow up. Thus, the detection of MRD at this time may have little value in the prediction of future relapse. However, at the end of treatment, children who remain in complete remission have no evidence of MRD. Conversely, detectable MRD at this time would seem to predict for future relapse, though this can be a delayed event. Remarkably, in two children who suffered a bone marrow relapse 8.5 and 9 years after completing therapy for their initial disease, MRD was detected, in their end of initial treatment marrow samples. Clearly PCR technology is changing the definition of the remission state in childhood ALL, and may have predictive value in the assessment of children who are at a high risk of future relapse. Large prospective studies of molecular monitoring are now required to confirm these preliminary results.

Adolescent↗