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R M Hardisty

Publications and source records attributed to R M Hardisty.

16 recordsLinked to original sources
PubMed1979

Bone marrow chromosomes in acute lymphoblastic leukaemia: a long-term study.

The bone marrow chromosomes of 25 children with acute lymphoblastic leukaemia (ALL) were examined at diagnosis before treatment, during remission, and in 12 cases, also during relapse. Follow-up was for at least six years. At diagnosis, 17 patients had a major population of chromosomally abnormal cells and of these 11 had identifiable clones. The commonest abnormality was hyperdiploidy. Eight patients had predominantly normal cells, but four of these had a minor abnormal clone. In remission, some samples were completely normal but, when pooled, remission samples had a minor population of chromosomally aberrant cells which were rarely clonal. The incidence of structural abnormalities was the same in patients who ultimately relapsed and those who remained in first remission at the end of the study, but the presence of hyperdiploid cells and/or clones in remission was more frequently associated with subsequent relapse. Relapse patterns were of two kinds: in three patients there was a return of the chromosomal abnormalities seen at diagnosis; in six others, chromosomal features in relapse were distinct from those at diagnosis. It is suggested that relapse associated with distinct chromosomal features may represent malignant transformation of a previously unaffected cell line. While chromosomal abnormalities seen prior to treatment can be related to the leukaemic event alone, abnormalities seen in remission and in relapse may result partly from drug and X-ray treatment. The relative importance of treatment and other factors to chromosomal change in ALL is discussed.

Bone Marrow↗
PubMed1979

[The platelet membrane: some aspects of the pathophysiology of haemostasis].

Platelet membranes play a key role in all stages of the haemostatic mechanism. Four of these in particular are considered here: adhesion to subendothelium, which involves an interaction between the glycoprotein I complex in the platelet membrane (deficient in the Bernard-Soulier syndrome) and plasma factor VIII; aggregation, involving the membrane glycoprotein IIb/IIIa complex (deficient in thrombasthenia), plasma fibrinogen and divalent cations; platelet factor 3 availability, a function of surface membrane phospholipids; and thromboxane synthesis, a function of the phospholipids of the membrane of the dense tubular system. The glycoprotein I complex also carries binding sites for thrombin and for drug-dependent antibodies, and glycoprotein IIb/IIIa is the site of the P1A1 antigen and of alpha-actinin.

Blood Platelet Disorders↗
PubMed1978

Prognostic implications of chromosomal findings in acute lymphoblastic leukaemia at diagnosis.

Chromosomes were studied on diagnostic bone-marrow samples from 39 children with acute lymphoblastic leukaemia (ALL). The patients were classified, according to the chromosomal characteristics of the major proportion of their leukaemia cells, into five categories; hyperdiploid, pseudodiploid, diploid, hypodiploid, and mixed. Patients in the hyperdiploid category had significantly longer first remissions than those in all other categories, and those in the pseudodiploid category had the shortest. Neither the absence of any normal cells nor the presence of detectable clones appeared to be an adverse feature. We suggest that the proportion of hyperdiploid cells, determined by conventional chromosomal staining techniques, may be used as an additional prognostic feature in childhood ALL.

Adolescent↗
PubMed1977

Long-term control of central nervous system leukaemia.

Seventy-four children with acute lymphoblastic leukaemia had one or more episodes of central nervous system (CNS) leukaemia. 5 children had CNS involvement at diagnosis; 4 survived for less than one year. In 35 children who had not had a previous bone marrow relapse on treatment and who received combination chemotherapy, the median duration of haematological remission from the time of first CNS relapse was almost 3 years. 5 children received full dose (2400 rads) craniospinal irradiation after their first CNS relapse; 4 have remained in CNS and haematological remission for 2 1/2 years or more. 18 children who had a CNS relapse after irradiation received 4-weekly intrathecal methotrexate; in 8 children this was given via an intraventricular reservoir. The median duration of CNS remission in children receiving intrathecal methotrexate was 2 years. Systemic and intrathecal treatment was stopped in 7 children after 2 1/2 years in continuous remission and in 2 children after 2 years. 4 of these 9 children remain in remission at intervals from 41 to 69 weeks off treatment but one is severely retarded. These results show that CNS disease is compatible with prolonged survival, but illustrate the difficulties of eradicating established CNS leukaemia.

Central Nervous System Diseases↗
PubMed1976

Epidemiology of childhood leukaemia in greater london: A search for evidence of transmission assuming a possibly long latent period.

Studies of space-time clustering of cases of childhood leukaemia have yielded equivocal results. This might be because the disease has a long and variable latent period, in which case the usual statistical tests for such clustering are inappropriate. A new statistical method is described which allows for such latent periods. For each patient, periods of "susceptibility" and "infectivity" are defined in which it is assumed he respectively "caught" and could "transmit" the disease. The measure of clustering is taken as the number of patients who were in the "right" place at the "right" time to "catch" the disease from another patient. This test is applied to childhood acute lymphoblastic leukaemia (death before age 6) in Greater London in the period 1952-65. Cases are postulated to be "susceptible" at various times before clinical onset of leukaemia, including in utero, and "infective" at various times around onset. Their effective "contacts" at these times are defined as circles of radius up to 4 km around their places of residence at these times. Slight evidence of clustering was found associated with certain of the defined times and distances, but the degree of clustering was small and could reasonably be attributed to chance. It is suggested, however, that this method of analysis might usefully be applied to other sets of such data. No evidence was found to add to our previously reported finding of space-time clustering of the dates and places of birth of children with leukaemia.

Child, Preschool↗
PubMed1976

Von Willebrand's syndrome. Studies on a variant factor VIII.

A girl with symptoms of von Willebrand's disease was found to have a slightly reduced or normal FVIII procoagulant activity, normal FVIII-related antigen (VIIIR:AG) and virtually absent von Willebrand's factor. The electrophoretic mobility of the VIIIR:AG in this patient's plasma and plasma fractions was increased and has been compared with that of two reported patients with FVIII variants. Her lysed platelets contained increased amounts of VIIIR:AG which had an increased anodal migration identical to her plasma VIIIR:AG. Experiments involving the selective absorption of a rabbit antiserum with the patient's plasma provide evidence that VIIIR:AG and von Willebrand's factor are immunologically distinct.

Adolescent↗
PubMed1975

Leukaemia in children and their grandparents: studies of immune function in six families.

Seven of 500 children with acute leukaemia seen over a 15-year period were known to have a close relative with leukaemia or lymphoma. In each case the affected relative was a grandparent of the child, six of the seven being paternal grandparents. Investigation of thses six families showed that the fathers, who had two affected first-degree relatives, had lower lymphocyte counts and higher serum IgA concentrations than paired controls. Atopy, repeated infections and rheumatic disease were common amongst the parents and their sibs. The findings suggest a possible immunodeficiency basis for leukaemia in these families and perhaps also for acute lymphoblastic leukaemia of childhood in general. In the only family in which three generations, including both leukaemic patients, were available for HL-A typing, the affected grandson had not inherited either of his affected grandmother's haplotypes.

Adolescent↗
PubMed1975

Chromosome banding studies in acute leukaemia at diagnosis.

Cytogenetic study by a chromosome banding technique has been attempted in 93 cases of acute leukaemia at diagnosis. Banding patterns were difficult to visualise in the bone-marrow chromosomes of patients with acute leukaemia because of the fuzzy appearance of the fixed metaphases. The proportion of patients with abnormal chromosomes was higher in acute lymphoblastic (ALL) than in acute myeloid (AML) leukaemia. Abnormalities were present in all cases of other cytological types. Hyperdiploidy was the most commonly found numerical error in both ALL and AML but a larger proportion of patients with ALL had hyperdiploidy in more than 30% of the cells. In ALL it was generally found that the higher the frequency of hyperdiploidy the greater was the number of chromosomes per cell. Hypodiploidy not attributable to random losses was found in only 6 patients. Clones identified by rearranged or marker chromosomes were found in all types of leukaemia. Clones marked by a 7q-chromosome, in which the break point was the same, were identified in 1 adult with ALL and 2 children with AML. The high frequency of randomly disturbed chromosomal breakage found in the bone-marrow chromosomes of a high proportion of the patients may be related to the disease process.

Adolescent↗
PubMed1975

Effect of oral contraceptives on factor VIII clotting activity and factor VIII related antigen in normal women.

The factor VIII clotting activity (VIIIc1 and factor VIII related antigen (VIIIRAg) were determined repeatedly in 24 pairs of age-matched normal women, one of each pair being on oral contraceptives. No significant differences in either parameter or in the VIIIc/VIIIRAg ration were found between the two groups ,although the mean factor VIII clotting activity and VIIIc/VIIIRAg ratios for women on oral contraceptives were very slightly higher than for those not on oral contraceptives.

Adult↗
PubMedDate not supplied

Acute lymphoblastic leukaemia in children: Classification and prognosis.

Immunological (surface-marker) tests have been used to define four subgroups of acute lymphoblastic leukaemia (A.L.L.) in childhood: T-A.L.L., B-A.L.L., common-A.L.L., and null-A.L.L. A study of 94 children shows that the common-A.L.L. subgroup achieves a much longer duration of remission than T-A.L.L.; our findings also confirm the association of some clinical features with T-cell A.L.L. Within the common-A.L.L. subgroup, initial white-cell count correlates with prognosis.

Adolescent↗