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Biomedical subjects

C D Reid

Publications and source records attributed to C D Reid.

At least 37 records · Page 2Linked to original sources
PubMed1993

In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease.

Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.

Amino Acid Sequence↗
PubMed1993

In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor.

XM323 represents a novel class of potent inhibitors of human immunodeficiency virus (HIV) protease. In vitro studies have shown that inhibition of this enzyme translates into potent inhibition of replication of HIV type 1 (HIV-1) and HIV-2. The inhibition of virus replication was assessed with three assays designed to measure the production of infectious virus, viral RNA, or p24 antigen. The production of mature infectious virions was measured with a yield reduction assay. By this assay, several strains and isolates of HIV-1 and HIV-2 were shown to be susceptible to XM323 in two lymphoid cell lines (MT-2 and H9) and in normal peripheral blood mononuclear cells, with a concentration required for 90% inhibition (IC90) of 0.12 +/- 0.04 microM (mean +/- standard deviation). The production of HIV-1(RF) RNA was measured with an RNA hybridization-capture assay. With this assay, XM323 was shown to be a potent inhibitor of HIV-1(RF) replication, with an IC90 of 0.063 +/- 0.032 microM. A third measure of virus replication, the production of p24 viral antigen, an essential protein component of the virion, was determined with the AIDS Clinical Trial Group-Department of Defense peripheral blood mononuclear cell consensus assay. This assay was used for expanded testing of XM323 against 28 clinical isolates and laboratory strains of HIV-1. XM323 was shown to be equally effective against zidovudine-susceptible and zidovudine-resistant isolates of HIV-1, with an overall IC90 of 0.16 +/- 0.06 microM.

Antiviral Agents↗
PubMed1993

[Usefulness of serology in the diagnosis of Candida tropicalis septicemia].

In this study, we have evaluated the usefulness of eight serologic tests in the diagnosis of a Candida tropicalis septicaemia in a patient with acute myeloid leukaemia. Among the tests used, detection of mannose and candida antigen in serum allowed a high degree of suspicion of infection, earlier than the isolation of this species on mycological cultures from blood or oesophagic samples. Detection of anti-C. albicans antibodies was useless but low titres of anti-C. tropicalis antibodies were observed. In spite of early diagnosis and antifungal treatment, the complication of the disseminated candidiasis with a Pseudomonas aeruginosa septicaemia, concluded with the patient's exitus.

Aged↗
PubMed1992

Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.

Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the structural attributes of Langerhans cells are observed in human bone marrow cultures in semi-solid media and are assumed to be the progeny of an early progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated growth of these cells has been studied using a chemically defined serum-free system to culture both unfractionated and highly enriched bone marrow progenitor cell populations. Although unfractionated cell growth was optimal in serum replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM) suboptimal proliferation of CFU-DL was observed in serum even in the absence of PHA-LCM. No colonies were observed under serum-free conditions when granulocyte-macrophage CSF (GM-CSF), IL-3, granulocyte CSF (G-CSF), and macrophage CSF (M-CSF) were present at levels optimal for granulocyte colony-forming unit (CFU-G) and macrophage colony-forming unit (CFU-M) growth. Addition of IL-1 alpha to these cytokines stimulated a small number of CFU-DL. However, in the presence of GM-CSF and IL-3, TNF-alpha or TNF-beta (5 U/ml) were both highly effective in promoting growth up to 82% of optimal and CFU-G growth was also enhanced at these concentrations. TNF was only active during the first 3 days of culture and higher concentrations of TNF-alpha but not TNF-beta were inhibitory for both CFU-DL and CFU-G. CD34+ cell-enriched populations were also enriched for both myeloid progenitors (CFU-G + CFU-M) and CFU-DL to 36- and 48-fold, respectively, and single cell cultures of CD34+ cells yielded single colonies containing both CD1a+ dendritic cells and CD1a- macrophages. Thus dendritic/Langerhans progenitors in the bone marrow expresses CD34, have a capacity for both macrophage and dendritic cell differentiation, and depend on hemopoietic growth factors and TNF for their further development in vitro.

Antigens, CD↗
PubMed1991

Plastic surgery audit codes: are the results reproducible?

The effective coding of data to produce a medical audit relies on agreement between the coders. This study was designed to assess whether coders can agree on codes for diagnosis and operations in a plastic surgery unit. Information from 50 patients was presented to a panel of six coders who were required to code the data using the International Classification of Diseases (ICD-9) and the Office of Population Census Studies (OPCS-4) systems. The results show that agreement between all the panellists occurred in only 32 out of 50 patients for one diagnostic code and 30 out of 50 for one operation code. When a patient had more than one diagnosis or operation, agreement was very much worse. Expert coders produced better results than the medical coders. The results are discussed with reference to other coding systems.

Abstracting and Indexing↗
PubMed1990

Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood.

Colonies of cells with distinctive dendritic appearance were observed in methylcellulose cultures of human bone marrow and peripheral blood mononuclear cells (PBMC). Such cells appeared alone in colonies of less than 50 cells, together with macrophages in mixed colonies and also within clusters of T lymphocytes at high culture cell numbers. The morphologic resemblance to lymphoid dendritic cells was confirmed by electron microscopy and the cells were distinguished from macrophages by immunoenzymatic and immunogold labeling with monoclonal antibodies (MoAbs). Like macrophages they were HLA-DR+ and CD4+. However, they lacked nonspecific esterase and the macrophage cytoplasmic marker Y1/82A. Most strikingly, cells were strongly HLA-DQ+ and expressed CD1a (T6), which is characteristic of skin Langerhans cells. Their functional similarity to lymphoid dendritic cells was demonstrated by their ability to stimulate allogeneic mixed leukocyte reactions. Dendritic cell colony numbers were estimated in both bone marrow and peripheral blood of controls and in leukemia and lymphoma patients before and after chemotherapy. Colony numbers were low in control blood and in patients before treatment (less than 1.0 to 3.7/10(5) cells). However, during hematopoietic recovery the mean value increased to 37.5/10(5) cells and this increase correlated closely with the observed increase in circulating colony forming unit-granulocyte macrophage (CFU-GM) in individual patients. Autoradiographic studies demonstrated mitotic activity within CD1a+ colonies and a linear relationship between cultured cells and both pure and mixed colonies was consistent with their derivation from a single precursor. These data indicate that a novel hematopoietic progenitor of dendritic/Langerhans cells (DL-CFU) may now be identified in a clonal assay system and suggest a probable common progenitor for these cells and macrophages.

Antibodies, Monoclonal↗
PubMed1990

A simple penile dressing following hypospadias surgery.

A single layer of surgical gauze applied with adhesive provides a simple and inexpensive dressing for use following hypospadias repair. It splints the penis to the abdomen, supports the wound and secures the catheter while permitting observation and wound care.

Bandages↗
PubMed1989

The recovery of circulating progenitor cells after chemotherapy in AML and ALL and its relation to the rate of bone marrow regeneration after aplasia.

Peripheral blood levels of BFU-e, CFU-GM and CFU-mix were studied serially in nine patients with acute leukaemia in remission during the period of recovery that followed induction or consolidation chemotherapy. Following 23 courses of treatment in the nine patients, the values for all three classes of progenitor were found to be higher in ALL than in AML (mean peak CFU-GM levels 5.8 x 10(3)/ml and 0.8 x 10(3)/ml respectively) and the highest levels were observed in patients recovering the most rapidly from bone marrow aplasia. Peak levels of these progenitors correlated best with the rate and extent of platelet recovery and all patients achieving blood levels of greater than 1.0 x 10(3) CFU-GM/ml had recovered greater than 100 x 10(9)/l platelets by 20 d and had peak platelet counts of greater than 400 x 10(9)/l within 40 d following chemotherapy. The peak values for circulating progenitors fell markedly after repeated courses of treatment in three of the five AML patients studied and this is likely to limit useful harvesting of such cells during later consolidation courses in this disease.

Adolescent↗
PubMed1989

Ranitidine fails to suppress the growth in vitro of haemopoietic progenitors from human peripheral blood or bone marrow.

Ranitidine was added in various concentrations (25-1600 ng/ml) to clonal assays of haemopoietic progenitors of normal human peripheral blood or bone marrow. Although a significant reduction in colonies forming from granulocyte-macrophage progenitors (CFU-GM) was demonstrated at the lowest drug concentration, no significant growth suppression was seen at higher concentrations. There was no evidence for growth inhibition of either erythroid progenitors (BFU-E) or pluripotent progenitors (CFU-mix) at any of the drug concentrations studied. A direct toxic effect of ranitidine on normal haemopoietic progenitors thus appears an unlikely cause of cytopenias observed during treatment.

Bone Marrow Cells↗
PubMed1989

Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics.

Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU-e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T1/2 range of 2.3 to 7.3 h. T1/2 after the first dose of r-HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment.

Adult↗
PubMed1988

The "tadpole flap"--its role in closure of palatal fistulae.

"Tadpole flaps" have been used in a series of 13 cleft palate patients in attempts to close anterior palatal fistulae over a 5-year period. The technique was successful in eight patients whose fistulae remained closed. The failures are discussed in detail.

Adolescent↗