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Biomedical subjects

J Tucker

Publications and source records attributed to J Tucker.

137 records · Page 8Linked to original sources

Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia.

Fourteen patients with poor-risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out-patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.

Administration, Oral↗

Acute myeloid leukemia in elderly adults.

One hundred and fifteen previously untreated adults aged over 60 years were referred to St Bartholomew's Hospital between 1978 and 1986 for management of acute myeloid leukemia (AML). Twenty-seven patients received symptomatic or palliative treatment only because combination chemotherapy was considered inappropriate. Eighty-eight patients received intensive chemotherapy with curative intent. There was a 48 per cent 'early death' rate and a 24 per cent incidence of resistant disease; complete remission (CR) was achieved in 25/88 patients (28 per cent). By multivariate analysis, a blast count less than 50 x 10(9)/l at presentation was the only factor predictive for achievement of CR whilst the latter and a presentation blast count less than 50 x 10(9)/l predicted for superior survival. Treatment was often curtailed on account of unacceptable toxicity; only 2/88 patients received the planned six cycles of treatment. Two patients died in CR. Four patients are alive in first CR at 3-9 years from treatment; one is alive in second CR following meningeal relapse. Overall survival was significantly worse than that of a contemporaneous group of adults aged 15-59 years treated at this hospital, but duration of CR was comparable. There are great difficulties involved in the intensive treatment of AML in elderly adults, but the major survival benefit gained by achieving CR should stimulate the search for better tolerated but still curative regimens.

Aged↗

Immunophenotype of blast cells in acute myeloid leukemia may be a useful predictive factor for outcome.

The immunophenotype of peripheral blood blast cells was tested in 92 patients with acute myeloid leukemia (AML), who were diagnosed and treated at single centre, St Bartholomew's Hospital, from 1978-1987 with a standard adriamycin, cytosine arabinoside and 6-thioguanine regimen. Immunological analysis involved standard fluorescence flow cytometry and utilized 31 monoclonal antibodies to known myeloid antigens (of CD groups 11b, 11c, 13, 14, 15, 16, w17, 31, w32, 33, 34, 35 and 36), a number of relatively less well studied antibodies with potential specificity for AML, and a series of control antibodies to T and B lymphocytes, platelets, erythrocytes and of widespread distribution (CD45, leucocyte common; HLA-DR). The results highlighted a number of antibodies with wide myeloid reactivity, in addition to CD13 and 33 (present in 66 per cent and 76 per cent of cases, respectively), which may be of immunodiagnostic use. A number of correlations between AML cell immunophenotype and FAB morphology subtype were found; in particular five antibodies (CD11c, 10.1, Tu3, CD15 and CD16), of both predominant granulocytic and monocytic reactivity, reacted with cells of AML-M5 subtype (p less than 0.05). There was no significant correlation between immunophenotype and clinical and pathological features at presentation. Correlation with clinical outcome was not a prominent feature, in contrast to some reports based on multicentre data. However, of particular note was the strong association between early death (at less than 2 months) and the coexpression of Leucocyte Function Associated (LFA) antigens, CD11b and 11c, on patient's blast cells (p = 0.003). The relationship was independent of clinical features and persisted even if AML-M5 cases were excluded. The significance of this latter finding is unclear, but may be related to the known role of CD11b and 11c LFA antigens in the cellular response to infection.

Adult↗

Effects of sorbinil treatment on erythrocytes and platelets of persons with diabetes.

Thirty-three diabetic subjects were given the aldose reductase inhibitor sorbinil (Pfizer, UK) for 3 wk. There was a significant fall in mean erythrocyte sorbitol concentration over this period. In all subjects erythrocyte sorbitol concentrations after treatment were within or below the range found in normal subjects. No changes in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) or myo-inositol concentrations, plasma beta-thromboglobulin (beta-TG) concentration, or P50--a measure of the oxygen affinity of hemoglobin--were observed. There was a high incidence of adverse reactions to the drug.

Adult↗

The use and value of third surgical opinions.

The results of new research into the contributions of third surgical opinions to health care quality and cost-effectiveness are reported by the Director and top Marketing and Research officers of the Health Benefits Research Center. As executives of the oldest second surgical opinion network in the U.S., the authors were able to test widespread beliefs about second and third opinion programs. Some, they found, did not hold up.

Cost-Benefit Analysis↗

The status of older adolescents at exit from out-of-home care.

Administrative data and case record reviews were used to assess the exit status of a sample of older youths leaving out-of-home care in one midwestern state. Results show that most left without a job or a high school diploma, and that many left with neither. The most common living arrangement at the time of exit was with relatives, some through planned reunification and some through unplanned reunification. The majority of the youths exited out-of-home care in unplanned ways. The number of placements and the completion of high school predicted employment status. High school completion was associated with age and a history of inpatient psychiatric care, running away, and mental retardation. Implications for independent living programs for older youths are discussed.

Adolescent↗

Cytokine gene transcripts for tumor necrosis factor-alpha, interleukin-2, and interferon-gamma in human pulmonary allografts.

BACKGROUND: Cytokines participate in host responses to allografts, largely through recruiting and activating various regulatory and effector cells. We performed this study to determine the feasibility of using polymerase chain reaction methodology to define the expression of three important cytokines (tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) in human pulmonary allografts. METHODS: Twenty-six graft-derived samples (11 transbronchial biopsy and 8 macrophage and 7 lymphocyte cell pellets isolated from bronchoalveolar lavage) were obtained from 13 lung transplant recipients and treated as follows: extraction of RNA; reverse transcription of RNA to complementary DNA; polymerase chain reaction amplification of cDNA with oligonucleotide primers specific for the three cytokines; gel electrophoresis of the polymerase chain reaction products; and verification of correct cytokine message by Dot blot technique (with specific 32P-labeled oligonucleotide probes). RESULTS: Concomitant pathologic evaluation of biopsy specimens from these 13 recipients showed five diagnostic groups: "normal" (no rejection/infection), n = 2; acute rejection, n = 4; nonspecific inflammation, n = 3; infection, n = 3; and obliterative bronchiolitis, n = 1. Interleukin-2 was expressed predominantly in acute rejection and infection (seven of ten and five of six samples positive, respectively), whereas tumor necrosis factor-alpha was expressed mainly in nonspecific inflammation (four of five samples) and somewhat less in rejection (six of ten). Interferon-gamma was expressed less frequently (in two of six samples with infection, but in none of ten with rejection and none of five with nonspecific inflammation). Serial data from one patient (6 months apart) showed considerable increase in interleukin-2 and interferon-gamma expression as she progressed from normal histologic status to obliterative bronchiolitis. CONCLUSIONS: Cytokine gene transcripts can be determined from minute samples derived directly from pulmonary allografts. Although our data are insufficient to make definitive conclusions, the suggestion of trends of cytokine expression in different posttransplantation pathologic conditions may indicate a useful role for this approach in the clinical evaluation of the lung transplant recipient.

Adult↗

Problems in assessing the relative predictive value of internal markers versus external exposure in chronic disease epidemiology.

Epidemiology traditionally has relied on measures of "external" exposure in determining the association between exposure and disease. Recently, there has been increasing reliance on internal markers reflecting internal dose and/or early stages of disease. In the context of observational studies of chronic disease in which there is a known exposure-disease association, the question arises whether the external exposure or the internal marker is a better predictor of eventual disease outcome. Here we describe some simple approaches to evaluate the relative predictive value of the internal marker (or biomarker, defined in the most general sense) versus the exposure, as well as their limitations. The problems of assessing the predictive value of internal markers for chronic disease are illustrated via two examples: (a) carcinogens, cytogenetic outcomes, and cancer; and (b) asbestos, asbestosis, and lung cancer. We conclude that it is unlikely that observational epidemiology will allow a full assessment of the predictive value of cytogenetic outcomes versus exposure for cancer in humans exposed to known carcinogens in the near future, although animal studies could provide important complementary information. For asbestos, data to date indicate that the presence or absence of asbestosis is a better predictor of lung cancer in an exposed population than is the level of exposure to asbestos itself. In general, the most useful markers for predicting chronic disease are ones which persist over time.

Animals↗

Survey of the development of laryngeal epithelium.

An overview of the developing laryngeal epithelium has been presented to establish the norm. The sequential relationships of the formation of the protective laryngeal covering, cellular and glandular, have been reviewed. The topographical distribution of the epithelial elements in the human larynx are illustrated in the adult and contrasted in the child. Unique and previously undescribed cellular ultrastructure and transition areas have been identified. Biological integrationof form and function is again well illustrated in the epithelium of the human larynx.

Adult↗