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Biomedical subjects

G C Yee

Publications and source records attributed to G C Yee.

At least 37 records · Page 2Linked to original sources
PubMed1989

Minimal risk of chronic renal dysfunction in marrow transplant recipients treated with cyclosporine for 6 months.

To determine whether 6 months of cyclosporine therapy is associated with chronic renal dysfunction, we evaluated serum creatinine concentrations 1 year post-transplant in 82 marrow transplant recipients randomized to receive either cyclosporine (n = 40) or methotrexate (n = 42) as graft-versus-host disease (GVHD) prophylaxis. Nine patients in the methotrexate group were later given cyclosporine as treatment for acute or chronic GVHD (methotrexate----cyclosporine). Cyclosporine prophylaxis was started on the day before marrow infusion, given at full doses until day 50, then gradually tapered and discontinued by day 180. Methotrexate prophylaxis was started on day 1 and given intermittently until day 102. Patients in the cyclosporine and methotrexate----cyclosporine groups had significantly higher mean serum creatinine values during the first 100 days post-transplant than methotrexate-treated patients, but by 1 year mean serum creatinine values were not significantly different between the three groups. Serum creatinine values at 1 year were also not significantly different from baseline values in each of the groups. None of the patients who had their cyclosporine discontinued by day 180 developed chronic renal dysfunction, defined as a doubling of the baseline serum creatinine at 1 year. We conclude that chronic renal dysfunction occurs rarely in marrow transplant recipients treated with 6 months of cyclosporine and when it does occur, it appears to have minimal clinical significance.

Bone Marrow Transplantation↗
PubMed1989

Colony-stimulating factors and tomorrow's pharmacy: why we must be ready.

The characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Colony-Stimulating Factors↗
PubMed1988

Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation.

To determine the relation between the serum cyclosporine concentration and the risk of acute graft-versus-host disease (GVHD), we studied 179 recipients of bone marrow grafts from HLA-identical sibling donors who received prophylaxis with cyclosporine, either by itself or combined with methotrexate. Cyclosporine was given either orally or intravenously at full doses from the day before transplantation until day 50; it was then tapered off and discontinued on day 180. Trough concentrations of serum cyclosporine were measured by radioimmunoassay. The relation between patients' characteristics and the risk of acute GVHD was analyzed with a relative-risk regression model. In 66 patients (37 percent), grades II to IV of acute GVHD developed 7 to 66 days (median, 13) after transplantation. The trough cyclosporine concentration for a given week was significantly associated with the risk that acute GVHD would develop during the following week. The relative risks were 0.7 (i.e., there was a 30 percent reduction in risk) for every increase of 100 ng per milliliter in cyclosporine concentration and 1.0, 0.60, and 0.20 for concentrations of less than 100, 100 to 199, and 200 or more ng per milliliter, respectively (P less than 0.01). A patient's age, prophylaxis regimen, and year of transplantation also influenced the risk of acute GVHD significantly. These data indicate that low cyclosporine concentrations can be a cause of treatment failure and that concentrations should be monitored in recipients of marrow transplants.

Acute Disease↗
PubMed1988

High-performance liquid chromatographic column-switching method for two cyclosporine metabolites in blood.

Cyclosporine (CSA) is biotransformed to many metabolites which may contribute to its immunosuppressive and nephrotoxic activity. We report a rapid and sensitive, automated column-switching high-performance liquid chromatographic (HPLC) method for measuring CSA-M17 in whole blood; the method also separates CSA-M1. CSA metabolite standards were isolated by a preparative-scale HPLC method. Samples were prepared by protein precipitation with acetonitrile followed by dilution with water. CSA-M17 was initially separated on a C8 column; final separation was on a C18 column. The inter-day relative standard deviation at 50 ng/ml was 8% (n = 3). Limit of detection was 20 ng/ml.

Biotransformation↗
PubMed1988

Blood cyclosporine pharmacokinetics in patients undergoing marrow transplantation. Influence of age, obesity, and hematocrit.

Blood cyclosporine pharmacokinetics were studied in 85 patients aged 1-52 (median: 22) years undergoing allogeneic bone marrow transplantation for the treatment of hematologic disease. Pharmacokinetic studies were carried out during the first two weeks posttransplant after an intravenous dose of 2.1-4.4 mg/kg. Whole-blood cyclosporine concentrations were measured by high-performance liquid chromatography. Multiple stepwise regression analysis indicated that age (P less than 0.001) and hematocrit (P less than 0.05) correlated with cyclosporine clearance (CL) while steady-state volume of distribution (Vss) did not correlate with any of the factors studied. Cyclosporine CL significantly differed among nonobese patients in different age groups; patients less than or equal to 10 years old had a higher mean CL (13.1 ml/min/kg) than patients 11-20, 21-30, 31-40, or greater than 40 years old (mean CL: 8.5-10.3 ml/min/kg) (P less than 0.05). No significant differences in cyclosporine CL and Vss were observed between obese (greater than 125% ideal body weight) patients and age-matched nonobese patients. Hematocrit values (range: 24-39) were inversely correlated with cyclosporine CL, which suggests that red blood cells function as important ligands in cyclosporine binding. These results show that blood cyclosporine CL is higher in marrow transplant recipients than in solid organ transplant recipients and that these differences may be related to lower hematocrits in marrow transplant recipients compared with solid organ transplant recipients. When compared with previously published serum cyclosporine CL data, our findings suggest that age-related changes in CL are primarily related to changes in plasma protein binding and that obesity does not significantly alter cyclosporine CL and Vss.

Adult↗
PubMed1987

Bone marrow transplantation.

Since the 1970s major progress in bone marrow transplantation has resulted in long-term survival and even cure for many patients with serious hematologic disease. Many patients undergoing the procedure, however, experience serious complications, including graft rejection, graft-versus-host disease, and infection. Preventing or treating these complications with drugs or other forms of immunotherapy is effective in many, but not all, patients.

Bone Marrow Transplantation↗
PubMed1987

Monitoring of cyclosporine therapy with in vitro biological assays.

We examined the correlation between cyclosporine (CsA) levels and in vitro assays of immune function and hematopoiesis. Mixed lymphocyte reaction (MLR), mitogen responses, suppressor cell (SC), cell-mediated lympholysis (CML), and erythroid colony (EC) assays were studied in dogs, and in vitro megakaryocytopoiesis was studied in mice. Serum CsA concentrations were measured by radioimmunoassay. After oral or intramuscular CsA dosing, lymphocyte proliferation, as measured by MLR, inversely correlated with in vivo serum CsA concentration. MLR responses decreased rapidly, and nearly complete inhibition coincided with peak CsA levels. While CsA concentration-related suppression of lymphocyte stimulation was also observed in mitogen-stimulated cultures, results were less predictable and similar to results with in vitro CsA addition, and higher serum CsA levels were required to achieve comparable suppression. In vivo serum or in vitro CsA levels greater than 300 ng/ml completely inhibited the development of cytotoxic effector cells but had no measureable effect on the expression of suppressor cells in the same cultures. Furthermore, CsA serum also caused concentration-related inhibition of EC growth. The addition of human embryonic kidney-conditioned medium, however, abrogated CsA-related inhibition of EC growth, which suggested that CsA indirectly inhibited EC growth, presumably by interfering with CsA-sensitive accessory cells. This was supported by studies in an in vitro model of murine megakaryocytopoiesis. In normal conditioned medium, megakaryocyte colonies were unaffected by the presence of CsA. However, when cells were cultured in conditioned medium prepared in the presence of CsA, profound inhibition of megakaryocyte growth was observed. These studies show that biologic assays can be used reliably to measure concentration-related changes in immunosuppressive activity of CsA. Further clinical studies are needed to evaluate the usefulness of pharmacodynamic monitoring of CsA therapy.

Animals↗
PubMed1987

Monitoring cyclosporin concentrations in marrow transplant recipients: comparison of two assay methods.

Renal dysfunction is the major dose-limiting toxicity associated with cyclosporin therapy. We have previously shown in patients undergoing allogeneic bone marrow transplantation that serum cyclosporin concentrations, as measured by radioimmunoassay (RIA), correlate significantly with the development of renal dysfunction. However, since the RIA measures both parent drug and metabolites, the relative role of each in the development of nephrotoxicity could not be determined. Therefore, we re-measured cyclosporin concentrations in the same serum samples by high-performance liquid chromatography (h.p.l.c.). Serum cyclosporin concentrations of less than 50, 50-100 and greater than 100 ng/ml, as measured by h.p.l.c., were considered equivalent to cyclosporin concentrations of less than 150, 150-250 and greater than 250 ng/ml, as measured by RIA. Contrary to results by RIA, cyclosporin concentrations measured by h.p.l.c. did not significantly correlate with renal dysfunction, which suggests that measurement of serum cyclosporin concentrations by h.p.l.c. provides no clinical advantage to RIA for monitoring cyclosporin concentrations to prevent renal dysfunction.

Adolescent↗