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Biomedical subjects

G Robbins

Publications and source records attributed to G Robbins.

15 recordsLinked to original sources
PubMed1992

A study of autologous blood collected after joint replacement surgery.

Blood from the surgical drains of 11 patients undergoing joint replacement was collected in the Solcotrans Orthopaedic autologous transfusion device and analysed for microparticulate matter before and after micro-aggregate filtration and for its effect on the coagulation of paired venous blood samples. An average of 165 ml (range 0-260 ml) was collected into the Solcotrans during the first hour. Using a Coulter Counter Zm particle counter, particulate matter of diameter 10-20 microns was found in only 2 of 10 collections at an average concentration of 33 x 10(3)/l. All units contained acoagulable blood [kaolin partial thromboplastin time (KPTT) greater than 600 s] but when mixed with paired post-operative venous samples exhibited the ability to shorten the KPTT by an average of 4.3 s inspite of the marked dilutional effect of mixing. Retransfusion of blood collected in the Solcotrans Orthopaedic device appears to be a suitable method to supplement or substitute pre-deposit and reduce exposure to homologous blood. Given the low incidence and concentration of microparticles detected, retransfusion of shed blood by this method is unlikely to cause significant pulmonary vascular occlusion resulting directly from deposition of microparticles.

Adult↗
PubMed1991

Diagnostic assessment of macrophage phenotypes in cardiac transplant biopsies.

Forty-one endomyocardial biopsies of the right interventricular septum have been investigated in 24 immunosuppressed patients after orthotopic heart transplantation. Monoclonal antibodies 27E10, 25F9, and RM3/1, which react with different macrophage phenotypes, and antisera MRP-8 and MRP-14, specific for proteins expressed on endothelial and monocyte cell surfaces in inflammation as well as markers for CD4+ and CD8+ T-lymphocytes, were employed in an indirect immunoperoxidase staining technique. This methodology permits more physiological recognition of the inflammatory process within the myocardium. It was possible to verify and to distinguish acute early, late and down-regulatory stages of inflammation in 33 biopsies (80%). No evidence of inflammation was found in seven biopsies (17%). Conventional histopathology with haematoxylin-eosin and Masson's trichrome was performed simultaneously, and demonstrated inflammation to be present in 23 of 41 biopsies (56%). An important findings is that CD4+ and CD8+ lymphocytes were absent in 15 of 41 specimens (37%) although there was inflammation proven by the presence of different macrophage phenotypes. The results indicate the necessity of long-term serial investigations of the physiological role of specific inflammatory macrophage phenotypes during the rejection process. It is concluded that the phenotyping of macrophage and endothelial cell differentiation antigens offers a sensitive approach to assess diagnosis of myocardial inflammation as a consequence of ongoing rejection in cardiac allografts.

Antibodies, Monoclonal↗
PubMed1990

Phospholipase A2 activation and autoinduction of tumor necrosis factor gene expression by tumor necrosis factor.

Tumor necrosis factor (TNF) acts via a cell surface receptor to induce a variety of cellular events including cytolysis, differentiation, and mitogenesis. The mechanisms underlying the cell specific actions of TNF are not known. In the present study, postreceptor events associated with the autoinduction of TNF expression were examined in HL-60 cells. There was no detectable alteration in phospholipase C activity as measured by inositol phosphate generation or release of choline metabolites following TNF stimulation. However, TNF increased the release of arachidonic acid metabolites from HL-60 cells. This increase in arachidonic acid metabolism was associated with a 40% increase in phospholipase A2 activity. Furthermore, the release of arachidonic acid metabolites was blocked by inhibitors of phospholipase A2. Taken together, these findings indicated that TNF stimulates phospholipase A2 and arachidonic acid metabolism in HL-60 cells. The results also demonstrate that TNF expression is induced 15-30 min after stimulation with TNF and that this effect is associated with an increase in the rate of TNF transcription. This autoinduction of TNF mRNA was blocked by inhibitors of phospholipase A2. While the cyclooxygenase inhibitor indomethacin had no detectable effect, ketoconazole and nordihydroguaiaretic acid, inhibitors of lipoxygenase, also blocked the induction of TNF expression by TNF. These findings suggest that phospholipase A2 and lipoxygenase activity are required for the transcriptional activation of TNF gene expression associated with TNF stimulation of HL-60 cells.

Acetophenones↗
PubMed1988

Prolonged high dose ARA-C infusions in acute leukemia.

High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.

Adult↗
PubMed1987

Detection of 1-beta-D-arabinofuranosylcytosine incorporation into DNA in vivo.

The incorporation of (1-beta-d-arabinofuranosylcytosine (ara-C) into the DNA of leukemic cells is highly correlated with cytotoxicity in vitro. However, the measurement of ara-C incorporation into leukemic cell DNA in vivo during ara-C therapy has been limited by the lack of a suitably sensitive method. A quantitative assay procedure has therefore been developed to determine incorporation of unlabeled ara-C into DNA. This method involves DNA isolation from patient myeloblasts, enzymatic digestion of the DNA, high pressure liquid chromatography separation of the nucleosides, and determination of ara-C in the eluate fractions by radioimmunoassay. Using this approach, incorporation of unlabeled ara-C into DNA of HL-60 cells is log linear over concentrations of 1 to 100 microM ara-C. Furthermore, the extent of ara-C incorporation into DNA as determined by this method correlates significantly with measurements of [3H]ara-C (DNA) formation under similar conditions. This approach has also been applied to clinical samples. Myeloblasts from 6 patients receiving high-dose continuous-infusion ara-C therapy incorporated 0.00-0.36 pmol ara-C/microgram DNA during 24 h of therapy. These findings thus suggest that this method can be used to monitor the in vivo incorporation of ara-C into leukemic cell DNA.

Adult↗
PubMed1986

Effects of cis-diamminedichloroplatinum on DNA incorporation and cytotoxicity of 1-beta-D-arabinofuranosylcytosine.

1-beta-D-Arabinofuranosylcytosine (ara-C) incorporates into replicating cellular DNA and the extent of this incorporation correlates with loss of clonogenic survival. More recent findings have demonstrated that incorporation of ara-C into DNA undergoing repair of damage induced by u.v. light also results in cell lethality. On the basis of previous studies demonstrating a marked synergism between cis-diamminedichloroplatinum (CDDP) and ara-C in LoVo colon carcinoma cells, the present work has examined the interaction of these agents at a biochemical and cellular level in the MCF-7 human breast carcinoma line. The extent of ara-C incorporation into MCF-7 DNA correlated significantly with loss of clonogenic survival in a dose-dependent manner. The effects of CDDP on the formation of MCF-7 (ara-C)DNA were monitored using both cesium sulfate and cesium chloride density centrifugation. The results demonstrate that CDDP had little, if any, detectable effect on incorporation of ara-C into DNA. Furthermore, combinations of CDDP and low concentrations of ara-C (10(-7) and 10(-6) M) decreased MCF-7 clonogenic survival in an additive but not synergistic manner. Modest synergy was detectable with CDDP and higher ara-C concentrations (10(-5) and 10(-4) M). The interaction between CDDP and ara-C was apparently dependent on concentration, duration of exposure and cell type. There was no dramatic synergy between CDDP and ara-C in MCF-7 cells. These findings may be relevant to the design and interpretation of CDDP/ara-C clinical trials.

Breast Neoplasms↗
PubMed1986

Incorporation of 9-beta-D-arabinofuranosyl-2-fluoroadenine into HL-60 cellular RNA and DNA.

The incorporation of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) into HL-60 cellular nucleic acids was monitored by cesium sulfate gradient centrifugation. The results demonstrated that F-ara-A incorporated into both RNA and DNA. These findings are in contrast to those previously obtained with 1-beta-D-arabinofuranosylcytosine (ara-C) and 9-beta-arabinofuranosyladenine (ara-A) which demonstrated incorporation of these nucleosides only in DNA. F-ara-A inhibited HL-60 proliferation, and the incorporation of F-ara-A into both DNA and RNA correlated with loss of clonogenic survival. Furthermore, cytostatic concentrations of F-ara-A resulted in the appearance of a more mature phenotype, a finding consistent with the effects of other inhibitors of DNA synthesis. The incorporation of F-ara-A into RNA and DNA should provide new insights regarding the mechanism of action of this agent.

Carboxylesterase↗
PubMed1985

Sequential studies on the role of mitoxantrone in the treatment of acute leukemia.

Mitoxantrone (Novantrone; 1, 4-dihydroxy-5, 8-bis [[2-[(2-hydroxyethyl) amino]ethyl]amino-] 9, 10 anthracenedione dihydrochloride (NSC 301739] is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias, ADJ-Pc6 plasmacytoma and a variety of solid tumours. In a phase I/II collaborative study fourteen consecutive patients with relapsed or primarily refractory acute leukaemia received a single infusion of mitoxantrone (20-32 mg/m2) at fourteen-day intervals. Antileukaemic activity was seen but there were no complete remissions and toxicity was minimal. Mitoxantrone was subsequently given in a five-day schedule at a dose of 10mg/m2 daily to twenty-one patients with relapsed or refractory acute leukaemia or chronic myeloid leukaemia in blast crisis (CML-BC). Four of five patients in first relapse of acute non-lymphoblastic leukaemia (ANLL) achieved a complete remission (CR). The overall response rate (CR + partial remission (PR] was 48%. In an ongoing phase III study the same (5-day) mitoxantrone treatment has been given in conjunction with a 7-day continuous infusion of cytosine arabinoside (Ara-C) in a kinetically designed schedule based upon the preclinical studies of the Mount Sinai group.

Acute Disease↗
PubMed1985

Continuous infusion of high-dose 1-beta-D-arabinofuranosylcytosine: a phase I and pharmacological study.

High doses of 1-beta-D-arabinofuranosylcytosine, administered as a continuous i.v. infusion, were evaluated in a Phase I trial in 14 patients with advanced solid tumors. 1-beta-D-Arabinofuranosylcytosine was given at 250 mg/sq m/h for infusions of 12 to 36 h. The mean steady state 1-beta-D-arabinofuranosylcytosine plasma level was 19.6 microM with a range of 9 to 59 microM. The principal toxicity was myelosuppression. An infusion of 18 h was well tolerated by most patients. A Phase II dose of 250 mg/sq m/h for 24 h can be used if platelet support is available. This dose schedule may be useful in the treatment of hematological disorders or in clinical combinations with DNA-damaging agents in the treatment of solid tumors.

Adult↗
PubMed1978

A computer program for parenteral nutrition solution preparation.

The preparation of single-bottle parenteral nutrition solutions for neonates has long posed a problem for pharmacists. Frequent formulation changes and the need for rapid supply of solutions after prescription has led to a variety of preparation techniques being developed. An interactive computer program is described which enables a nonspecialist pharmacist staff to safely and quickly produce the formula, label and fully document it from a prescription for parenteral nutrition. Ordered quantities are expressed in amounts required per kilogram per 24 hours, and are input to a computer using a "prompt" system. Features of the program include automatic compensations for all non-amino acid ingredients of a variety of commercial amino acid solutions; specified or unspecified chloride anion input; and logic checks which are tied to physiologie "danger" levels, signaling to the operator when "greater than a critical level" has been requested by the prescriber, as well as the conventional check of the logic. The program has allowed infinite variability to prescribing of all ingredients of parenteral nutrition, extremely rapid and accurate production of formulate and allows the computer storage of data about nutritional input to patients. The program is extremely simple in operation, and gives significant cuts in lag time between prescription and the commencement of the new formula.

Carbohydrates↗
PubMed1976

Correlation between estrogen receptor protein and carcinoembryonic antigen in normal and carcinomatous human breast tissue.

We determined estrogen receptor protein and carcinoembryonic antigen in cytosols prepared from 189 human breast carcinoma tissues, 85 benign or normal breast biopsies, and 101 tissue specimens metastatic from breast carcinoma. Carcinoembryonic antigen was observed in 70% of the primary carcinomatous tissues, 15% of the benign or normal specimens, and 51% of the metastases. Ninety-six of the 189 primary carcinomatous specimens with increased concentrations of carcinoembryonic antigen were also positive for estrogen receptor protein, whereas 67 of the 72 benign or normal biopsies with low concentrations of carcinoembryonic antigen were also negative for estrogen receptor protein. All five fenign specimens with positive estrogen receptor protein and normal carcinoembryonic antigen concentrations were from fibroadenomas. The concordance between estrogen receptor protein and carcinoembryonic antigen in the primary carcinomatous tissue was 66%, in metastatic carcinoma 51%, and in benign and normal tissue 85%.

Breast↗