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Biomedical subjects

P Alexander

Publications and source records attributed to P Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1984

Serum neuroleptic concentrations and clinical response: a radioreceptor assay investigation of acutely psychotic patients.

Twenty-two acutely psychotic patients were rigorously assessed for psychopathology at baseline and after 14 days of neuroleptic treatment. The neuroleptic radioreceptor assay (NRRA) was used to determine serum neuroleptic concentrations. Serum neuroleptic concentration was significantly, nonlinearly related to changes in BPRS Total Score, and BPRS Factor Scores for Thought Disturbance and Anxiety-Depression. Clinical improvement was associated with intermediate (11-50, 51-126 ng/ml haloperidol equivalents) while poor clinical outcome was related to both low (less than or equal to 10 ng/ml) or high (greater than 125 ng/ml) serum levels. The results are discussed in terms of a possible "therapeutic window" for the neuroleptics and the implications this might have for clinical practice.

Adolescent↗
PubMed1984

Women, labour and fertility: population growth in nineteenth century Java.

The sharp increase in Java's population after 1830 is usually explained in terms of higher living standards and consequent lower mortality resulting from Dutch colonization, but there is little historical evidence supporting such an interpretation and much to refute it. An alternative view is that Java's population growth after 1830 was due to increasing fertility. The major constraint to Javanese fertility prior to this period has been extended periods of postpartum abstinence, the length of which was determined by the duration of breastfeeding, because people believed semen had deleterious effects on breast milk. In 1830 a system of forced cultivation of export crops was imposed by the Dutch rulers and greatly increased the amount of labor which Javanese households required to reproduce themselves. The arduous work women began to undertake made it increasingly difficult to breastfeed their children. As the average period of breastfeeding fell, the average period of postpartum abstinence declined and fertility increased.

Agriculture↗
PubMed1984

Host factors in metastasis: immunostimulatory action of retinoids.

Many host factors contribute to the death of cells shed from cancers and with many immunogenic tumors immune control is decisive in determining the incidence of metastasis. Although an aromatic analogue of retinoic acid did not affect the growth of nonimmunogenic carcinomas or sarcomas it slowed the tumor growth of immunogenic cancers but only if they were grown in immunocompetent hosts. A working hypothesis is that retinoids enhance the magnitude of a T-cell dependant host response to the tumor and it is this that causes the inhibition of growth. If the animals are rendered incapable of evoking a T-cell response then retinoids are unable to influence tumor growth.

Animals↗
PubMed1983

Effect of cyclosporin A on the anti-leukaemia action associated with graft-versus-host disease.

Graft-versus-host disease (GVHD) was induced in Hooded (Rt1c) strain rats by means of high dose total body irradiation (TBI) and subsequent reconstitution with allogeneic bone marrow and spleen cells from WAG (Rt1u) strain donors. Untreated recipients of allogeneic cells died within 20 days of engraftment, whereas those treated daily with Cyclosporin A (CyA), given either from the day receipt of the graft (Day 0) or from Day 4, survived until the end of the experiment (Day 50). If delayed until Day 7, CyA prophylaxis was totally ineffective. Hooded rats bearing a syngeneic leukaemia were irradiated and reconstituted with allogeneic bone marrow. During the course of the ensuing graft-versus-host response (GVHR) leukaemia cells were eradicated from the spleens of the host animals. However, as a consequence of CyA prophylaxis, whether started on Day 0 or delayed until Day 4, the anti-leukaemia potential of the bone marrow allograft was completely abrogated. Anti-tumour activity after engraftment was detectable first at Day 7, i.e. the time at which the GVHR became intractable to the effects of CyA. The results indicate (1) that CyA suppresses the initial events but not the effector phase of the GVHR, and (2) that the anti-host and anti-tumour action of the GVHR may be temporally inseparable.

Animals↗
PubMed1983

Role of "lymphotoxin" in the local anti-tumour action associated with inflammation caused by delayed hypersensitivity responses or intralesional BCG. I. Variations in response of different syngeneic mouse tumours.

The anti-tumour effect induced by a delayed hypersensitivity response (DHSR) unrelated to the tumour or by intra-tumoural inoculation of BCG was studied with 6 syngeneic mouse tumours. The growth of the tumours was followed i.p. or s.c. in suitably sensitized animals either in the presence or absence of the specific antigen required to elicit a DHSR. In a Winn-type assay the growth of tumour cells admixed with sensitized lymphocytes was also determined with and without the eliciting antigens. In addition, the effect of admixing different amounts of BCG with the tumour cells was studied on the growth of the tumours in vivo. The different tumours varied widely in their susceptibility to growth inhibition by a DHSR reaction and by BCG but their order of sensitivity was the same in all of the tests. Analysis of the effector population in the Winn test coupled with the inability to observe an anti-tumour action in mice with defective T-cell function showed that the effector mechanism involved allergized T-cells or more probably products released when these were confronted with the specific antigen. In vitro the relative susceptibility of the different tumour cells to killing by activated macrophages and by NK cells was quite different to that found for in vivo growth inhibition but the in vitro response to lymphotoxin of the different tumours paralleled that produced by inflammation in vivo.

Animals↗
PubMed1982

Failure of short-term treatment with flurbiprofen to enhance the therapeutic effect of cyclophosphamide against rodent sarcomas and a leukaemia.

Animals bearing metastatic fibrosarcomas were treated with cyclophosphamide (CY) alone or in combination with flurbiprofen (FP), an inhibitor of prostaglandin synthesis. FP did not affect local growth of fibrosarcomas, and the incidence of distant metastases after resection of the "primary" implants was comparable in treated and control groups. Treatment with CY retarded growth of the fibrosarcomas and reduced the proportion of animals which succumbed to metastases, but this was not altered significantly by additional treatment with FP. FP did not affect the survival of rats bearing a lymphoid leukaemia. The lifespan of animals treated with CY was increased significantly, but the concomitant administration of FP did not enhance this effect.

Animals↗
PubMed1982

2nd Gordon Hamilton Fairley lecture. Need for new approaches to the treatment of patients in clinical remission, with special reference to acute myeloid leukaemia.

A serious limitation of chemotherapy for acute myeloid leukaemia (AML), Hodgkins disease and some classes of breast cancer is that, even when clinically evident disease responds well, the same chemotherapy when given during remission does not affect the rate of relapse after chemotherapeutic or surgical ablation of the primary disease. This cannot, in general, be caused by genetic adaptation of the residual cancer cells which renders them resistant to specific drugs, because after relapse further remissions can be obtained with the same drugs that were ineffective by chronic administration in prolonging remission. The resistance of the residual cells may arise from mechanisms such as inaccessibility for anatomical or other reasons, or because of a change in metabolic state which causes these cells temporarily to cease division, when they cannot be harmed by cycle-dependent drugs and repair damage sustained from cycle-independent drugs. Limited differentiation has been shown capable of reversal and this may be a mechanism which leads to quiescence and associated "resistance", particularly in the case of AML. Where such resistance occurs treatment during remission-or as an adjuvant to surgery and radiotherapy-may have to rely on mechanisms which are independent of cellular proliferation such as processes associated with graft-versus-host-disease or the induction of terminal differentiation. A model for studying the nature of resistance of residual cancer and for testing treatments that might be active against cancer cells in this state may be dormant metastases. The latter are malignant cells which appear to be in peaceful co-existence with their host and which in experimental systems have been induced to grow into lethal metastases by perturbation of the host by surgical trauma, by hormonal manipulation or by immunosuppression.

Animals↗
PubMed1981

Maturation of human peripheral blood leukemic cells in short-term culture.

This work is a continuation of earlier studies in this laboratory (Palú et al. 1979) in which two populations of cryopreserved acute myelogenous leukaemia (AML) cells were shown to undergo progressive maturation in vitro. Twelve other populations of AML cells have since been studied and three distinct patterns of in vitro behaviour have been observed: 1. Cells which did not mature. 2. Cells which matured to the polymorph series and 3. Cells which matured to the macrophage series. Six populations of AML cells were studied both before and after cryopreservation to demonstrate that exposure to the cryopreservative agent dimethylsulphoxide (DMSO) does not influence the patterns of maturation observed. The effect of thioproline and prostaglandins A1 and A2 on maturation was also studied. It is too early to say whether any correlation between the prognosis of the AML patients and the maturation pattern of their AML cells can be established.

Cell Count↗
PubMed1981

Gamma-hydroxybutyrate treatment of schizophrenia: a pilot study.

Gamma-hydroxybutyrate (GHB) was administered to seven chronic schizophrenic patients in the first double-blind, placebo-replacement trial of this compound. No significant drug effect in this group was obtained. Two patients became nonpsychotic during the drug trial, three got worse and two patients did not respond. The two patients who responded with improvement were augmenters, as measured by average evoked potential (EP), had low platelet MAO activity and high cerebrospinal fluid (CSF) homovanillic acid (HVA). A number of patients developed akathisia and dystonia during the trial, especially after receiving probenecid for lumbar puncture. Further study is warranted, possibly in a selected patient group.

Double-Blind Method↗
PubMed1981

Mechanism of the local antitumor action of inflammation.

Some but not all tumor cells are killed in the environment of a delayed hypersensitivity reaction (DHSR) induced by antigens unrelated to the tumor. Of the several cytotoxic components, cellular and humoral, which are present at the site of a DHSR, a lymphokine released by the interaction of specific antigen with immune T cells-presumptively lymphotoxin-was shown to be responsible for the antitumor action of DHSR. The same mechanism may account for the failure of some tumor cells to grow when inoculated in admixture with BCG.

Animals↗
PubMed1980

Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation.

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.

Adolescent↗
PubMed1980

Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours.

Cyclosporin A (Cy A), a novel immunosuppressive agent with apparently selective inhibitory effects on T lymphocytes and little myelotoxicity, was tested for its effects on a variety of syngeneic animal tumours including sarcomas, carcinomas and a T-cell lymphoma. Cy A, given orally or parenterally in repeated doses, had no effect on the growth rates of any of the tumours tested, but a highly significant effect on metastasis was seen in many cases. All the sarcomas examined in both rats and mice, and also the lymphoma, showed a marked increase in their metastases, in some cases even when administration of Cy A was delayed until after excision of the "primary" tumour implants. In contrast no effect of Cy A on metastasis was observed in animals bearing poorly immunogenic mammary or squamous-cell carcinomas. The metastases developing in Cy A-treated animals, when transplanted into normal syngeneic animals, showed no evidence of enhanced metastatic potential compared with their "parent tumours.

Administration, Oral↗
PubMed1980

Failure to detect autologous antibodies in the remission sera of patients with AML: complications introduced by the presence of rheumatoid factor.

Sera were collected from patients with acute myelogenous leukaemia (AML) at various times during remission induced by chemotherapy, but after cessation of all immunosupressive treatment. These sera were tested, by a sensitive assay using radio-labelled antiglobulin binding, for the presence of antibodies which bound to the surface of autologous AML cells. The cell populations examined were chosen on the basis that they proliferated in short-term culture, did not bind anti-Ig reagents directly, and that more than 80% of the cells did not carry detectable Fc receptors. With 8/9 patients studied, no specific antibodies of the IgG or IgM class could be detected in serum samples taken during remission. IgG and IgM antibodies from the remission sera of one patient were found be bind to autologous leukaemic cells, but this was found to be due to the presence of rheumatoid factor (RF) and removal of the RF activity abolished this binding. This study has, like others, failed to detect autologous antibodies, in remission sera, that are directed against membrane components of AML cells.

Antibodies, Neoplasm↗
PubMed1980

Mechanism by which antibodies to non-AgB antigens mediate rejection of rat leukaemia cells.

The August and Hooded rat strains are compatible at the major histocompatibility locus (both are AgB5 or Rtlc). Antisera against the minor histocompatibility antigens of Hooded rats were raised by immunizing August rats with grafts of tumours or normal tissue. Such antisera, if transferred to normal unimmunized August rats, cause them to reject i.v. administered Hooded rat leukemia (HRL) cells within a few hours, and X-irradiated August rats, for whom a graft of HRL is lethal, can survive indefinitely if pretreated with the antiserum. The distribution of 125I-labelled HRL cells in the tissues of August rats was followed at times after their injection, and it was found that, in the presence of antiserum, i.v. administered leukaemic cells are rapidly destroyed in the liver and spleen. The active component of the antiserum is IgG antibody, and its action is independent of the lytic elements of complement. Antibody-mediated splenic and hepatic clearance of the leukaemia cells is unaffected by total-body X-irradiation but reduced by treating the rats with colloidal carbon. The data are consistent with the hypothesis that the rejection of HRL across the histocompatibility barrier studied is, in the presence of antibody, effected by immunophagocytosis.

Acute Disease↗