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Biomedical subjects

G Crooks

Publications and source records attributed to G Crooks.

8 recordsLinked to original sources
PubMed2000

Gene therapy for adenosine deaminase deficiency.

The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (d) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.

Adenosine Deaminase↗
PubMed1998

T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates.

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.

Adenosine Deaminase↗
PubMed1998

Hematopoietic stem cell transplantation for primary lymphoid immunodeficiencies.

Hematopoietic stem cell (HSC) transplantation is curative therapy for many primary immunodeficiencies. All forms of severe combined immune deficiency (SCID) can be cured, but the extent of the immunologic correction is dependent on the pathophysiology of the primary defect. Defects involving lymphocyte differentiation are more easily corrected than defects in lymphocyte function because a selective advantage exists for the progeny of the normal donor HSC when the primary defect affects lymphocyte differentiation. T-cell-depleted (TCD), haploidentical-HSC transplantation can cure many forms of SCID, but not other primary immunodeficiencies like the Wiskott-Aldrich syndrome (WAS). Unrelated bone marrow and umbilical cord blood are alternative sources of HSC for patients who do not have histocompatible donors.

Hematopoietic Stem Cell Transplantation↗
PubMed1978

Drug prescribing patterns in the elderly: a cross-sectional study of in-patients.

A cross-sectional one-day survey of drug prescribing and use in elderly in-patients was carried out in Dundee hospitals. Altogether 873 patients were studied and analyses of prescribing patterns were carried out by patient categories--medical, surgical, geriatric, psychiatric and mentally subnormal--and by major drug groups. While the average number of drugs prescribed per patient on the study day was 3.3, which was not excessive, other results highlighted some possible problems of therapy, viz. the wide range of drugs used within drug groups, the common use of psychotropic drugs, dose regimes which although used in a geriatric population differed little from general adult dosages, and which sometimes involved many administrations per day. Examples were described relating to the use of nitrazepam, phenothiazines and tricyclic antidepressants.

Aged↗