Search PubMed⌕ Search

Biomedical subjects

J C Yau

Publications and source records attributed to J C Yau.

At least 37 records · Page 2Linked to original sources
PubMed1991

Therapeutic drug monitoring of cyclosporine-lipoprotein levels.

Cyclosporine therapy is complicated by nephrotoxicity that is not predicted by drug levels. In this study serial trough blood samples were obtained from 11 allogeneic marrow transplant recipients after initiation of intravenous cyclosporine 2 mg/kg every 12 hours for a period extending 4 weeks after transplantation. Renal dysfunction, assessed by an increase in serum creatinine levels to twice baseline values or when greater than 175 mumol/L, was found in four patients. No associations between renal dysfunction and cyclosporine levels in whole blood, total plasma, or lipoprotein fractions were found. The ratios of maximum and mean high-density low-density lipoprotein cyclosporine concentrations were greatest in patients with renal dysfunction (p less than 0.001). The data suggest therapeutic drug monitoring of cyclosporine in various biologic fluids does not predict onset of drug-associated renal dysfunction. However, the relative role of high-density to low-density lipoprotein transport of cyclosporine may provide an index of renal functional changes associated with the agent.

Adolescent↗
PubMed1990

Longitudinal study of cyclosporine and lipids in patients undergoing bone marrow transplantation.

The metabolic effects of intravenous cyclosporine on lipids and lipoproteins were studied in 29 allogeneic bone marrow recipients compared with 13 autologous bone marrow patients not requiring cyclosporine therapy. Patients were monitored continuously from 5 days prior to 27 days following transplantation; cyclosporine treatment was initiated 4 days before transplantation. Fasting lipid and lipoprotein levels were measured in serial blood samples throughout the study period. Nutritional supplementation, conditioning regimens and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline between the patient groups. Cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels remained unchanged in autologous patients. As compared with baseline values, plasma total cholesterol increased by an average of 26 percent in allogeneic transplantation patients receiving cyclosporine. Similarly, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol was fourfold greater in those patients treated with cyclosporine compared to the autologous group. We conclude that cyclosporine appears to elevate cholesterol levels. Neither acute graft vs host disease nor changes in hepatic function could explain the differences in plasma cholesterol levels between groups.

Adult↗
PubMed1990

Single-dose cyclosporine pharmacokinetics in various biological fluids of patients receiving allogeneic marrow transplantation.

The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population.

Adult↗
PubMed1990

Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support.

We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.

Adult↗
PubMed1990

High dose cyclophosphamide, BCNU and VP-16 with autologous blood stem cell support for refractory multiple myeloma.

Eleven patients with advanced multiple myeloma refractory to standard doses of alkylating agents and salvage therapy with vincristine, adriamycin and dexamethasone (VAD) were treated with high dose cyclophosphamide, BCNU and VP-16 (CBV) with autologous blood stem cell support. Seven patients had marked marrow plasmacytosis (greater than 30%) and four had extensive pelvic bone disease precluding autologous marrow harvest. Four patients responded with a median remission duration of 7 months. Recovery of granulocytes and platelets occurred promptly in 10 evaluable patients with complete hematologic recovery. Autologous blood stem cells can provide safe and effective support for high dose CBV treatment of myeloma patients with extensive marrow plasmacytosis. The short remissions call for better cytoreductive regimens with consideration for earlier use when the myeloma may be more responsive to therapy.

Blood Transfusion, Autologous↗
PubMed1990

Increased sensitivity in a radioimmunoassay for measuring cyclosporine in lipoprotein fractions.

We describe a modification of the commercially available cyclosporine (CAS) 3H-RIA kit, allowing detection of drug in lipoprotein fractions obtained by ultracentrifugation. Sodium bromide solutions containing the lipoprotein fractions were dried and reconstituted with drug-free plasma. Methanolic extractions were centrifuged, and 250 microL of the supernate was dried and reconstituted with 50 microL of methanol. Buffer, radioactive tracer, and monoclonal antibody were then added and incubated for 2 h at 4 degrees C. Samples were subjected to charcoal de-activation and then centrifuged, and the radioactivity in the supernate was counted. The limit of detection of CSA was 2.5 micrograms/L; analytical recovery was between 97.5% and 101.3%. Within- and between-day CVs were less than 9%. We conclude that the present method may be beneficial for therapeutic drug monitoring of CSA in lipoprotein fractions.

Analysis of Variance↗
PubMed1990

Purging of T-lymphocytes with magnetic affinity colloid.

There is a well-documented correlation between the number of T-lymphocytes in the bone marrow graft and subsequent development of acute graft-versus-host disease after allogeneic bone marrow transplantation. The incidence of acute graft-versus-host disease may be decreased with elimination of mature T-lymphocytes from the bone marrow graft. We have developed an immunomagnetic separation procedure using an avidin-based magnetic affinity cobalt colloid. Bone marrow cells were incubated with a combination of CD2, CD3, CD4, and CD8 monoclonal antibodies. The cells were washed and then incubated with the biotinylated, affinity-purified IgG fraction of goat anti-mouse immunoglobulins followed by an avidin-based magnetic affinity colloid. The cells were then run through a high-magnetic gradient separation column utilizing an external samarium cobalt magnet. The number of residual T-lymphocytes was assessed by limiting dilution analysis of clonogenic T-lymphocytes. This procedure produces an approximately 1.7-log reduction of antibody-reactive cells with 45% recovery of hematopoietic progenitors (granulocyte-macrophage colony-forming cells, GM-CFC). This causes a reduction of T-lymphocytes in the bone marrow graft to approximately 5 x 10(5) cells/kg body weight.

Antibodies, Monoclonal↗
PubMed1990

Methylprednisolone, cyclosporine and methotrexate for prophylaxis of acute graft-versus-host disease.

Twenty-four patients were given the combination of methylprednisolone 100 mg i.v. on day 0, cyclosporine 2 mg/kg i.v. every 12 h starting on day -3 and methotrexate 5 mg/m2 on days 1, 3, and 6, then 10 mg/m2 on days 11 and 18 after allogeneic bone marrow transplantation for hematological malignancies for the prophylaxis of acute graft-versus-host disease. (GVHD). Methylprednisolone was given prior to the marrow infusion for its lympholytic effect. The methotrexate dose on days 1, 3, and 6 was half of that given in other studies to decrease the early toxicities. The outcome of this group is compared with patients transplanted before 1988 and given methotrexate alone, methotrexate with prednisone, or cyclosporine alone. There is no difference in relapse and survival between the groups at this time. The rate of engraftment and incidence of mucositis with the combination is not significantly different from the cyclosporine group. No patient developed greater than grade II acute GVHD with the combination. The probability of grade II or higher acute GVHD with the combination (14%) is significantly less than methotrexate, with or without prednisone or cyclosporine alone.

Adolescent↗
PubMed1989

Steroid-responsive chronic hepatic graft-versus-host disease without extrahepatic graft-versus-host disease.

A 29-yr-old woman developed severe, progressive cholestasis 5 months after allogeneic bone marrow transplantation. Extrahepatic graft-versus-host disease (GVHD) was absent. Skin biopsy was equivocal 2 months after transplant, rash was absent during the period of cholestasis, and cholangiographic abnormalities were absent. Liver biopsy 7.5 months posttransplant revealed chronic hepatic GVHD. Cholestasis dramatically resolved with high dose corticosteroid therapy. Chronic hepatic GVHD occurs in the absence of overt extraintestinal GVHD and respond promptly to therapy. This underscores the importance of aggressive diagnostic evaluation of posttransplant cholestasis.

Adult↗
PubMed1988

Chemotherapy following surgery for stages IE and IIE non-Hodgkin's lymphoma of the gastrointestinal tract.

Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). The primary site included stomach (16 patients), small bowel (seven), large bowel (two), and mesenteric nodes (one). Following surgery, nine patients had macroscopic and four patients had microscopic residual disease, and 13 were felt to have had complete surgical resection. Thirteen patients were stage I and 13 were stage II. Sixteen patients were treated with COPP (cyclophosphamide, vincristine, procarbazine, prednisone), nine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and one with CVP (cyclophosphamide, vincristine, prednisone). At a median follow-up of 50 months (8+ to 178+ months) ten of 12 stage I patients and nine of 14 stage II patients remain alive. Of the nine patients with macroscopic residual disease, four died of disease 6.5 to 11.0 months after diagnosis, and five are alive 8+ to 178+ months from diagnosis. Fourteen of the remaining 17 patients who had complete surgical resection are alive without disease. Death in the other three patients was due to multiple abdominal abscesses at 12 months, adenocarcinoma of the colon at 57 months, and dementia and progressive neurologic dysfunction at 65 months. No patient who had complete resection has relapsed or developed systemic disease after chemotherapy. These results suggest that complete surgical resection is an important prognostic factor and that chemotherapy without irradiation in completely resected localized GI-NHL can prevent local and systemic relapse resulting in long-term disease-free survival.

Adult↗
PubMed1987

Cyclophosphamide, doxorubicin, and vincristine in etoposide- and cisplatin-resistant small cell lung cancer.

For two chemotherapy regimens to be truly non-cross-resistant, each should be active as first-line therapy and also as second-line therapy. The effectiveness of both cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide and cisplatin (VPP) in previously untreated patients with small cell lung cancer has been well-documented. Also, VPP has caused tumor regression in up to 50% of patients when used as second-line therapy after CAV. The effectiveness of CAV after progression or relapse after VPP has not been documented. We identified 29 patients who received CAV after their tumors failed to respond or relapsed after VPP or etoposide and carboplatin (VPC). There were 21 male and eight female patients (median age, 57 years; range, 30-79). Thirteen patients were treated following failure to respond to VPP or VPC and 16 at the time of relapse. Eight patients had limited disease and 21 had extensive disease. Metastatic sites included liver (11 patients), bone (ten), lymph nodes (seven), bone marrow (three), brain (four), and contralateral lung (one). There were three complete responses (durations of 16, 22, and 26 weeks) and five partial responses (duration, 8+ to 36 weeks). Three patients had stable disease and 18 patients had disease progression while receiving treatment. The median survival of the entire group was 15 weeks. Responding patients had a median survival of 34 weeks (range, 8+ to 72+) and stable and nonresponding patients had a survival of only 9 weeks (range, 2-38). A granulocyte count nadir less than 500 X 10(9)/L was seen after 7.9% of evaluable treatment cycles and a platelet count nadir less than 50,000 X 10(9)/L occurred after only 5.3% of cycles. Five patients required transfusion for anemia, and two patients required dose reduction of vincristine for peripheral neuropathy. This study demonstrates that CAV has limited activity following failure to respond to VPP.

Adult↗
PubMed1986

Regeneration of T lymphocytes from human bone marrow cells after depletion with methylprednisolone.

This study evaluates the propagation of T lymphocytes in bone marrow cells after in vitro methylprednisolone treatment. Previous studies from this laboratory showed that immunocompetent T lymphocytes could be eliminated from the bone marrow cells by incubation with 15 mg/ml (0.04 M) of methylprednisolone for 1 hr. The effectiveness of the chemoseparation was assessed by E-rosette forming cell assay, mitogen-induced lymphoblastogenic responses, and lymphocyte surface markers. In this study, bone marrow cells treated with different concentrations of methylprednisolone were cultured in the presence of PHA and Interleukin-2. The mitogen-induced lymphoblastogenesis was restored in the 15 mg/ml MP-treated bone marrow cells by the 8th day of culture in the presence of Interleukin-2. The cells in the culture were analyzed by E-rosette forming cell assay. It was shown that the predominant cells in the cultures were E-rosette forming cells. This study demonstrates that immunocompetent T lymphocytes can be regenerated in the presence of mitogen and Interleukin-2 from bone marrow cells treated with 15 mg/ml of methylprednisolone.

Bone Marrow↗
PubMed1985

A comparative randomized trial of vinca alkaloids in patients with metastatic breast carcinoma.

The therapeutic efficacy of vincristine, vinblastine, and vindesine were evaluated in a prospective randomized trial in patients with metastatic breast carcinoma. All patients were refractory to doxorubicin-containing chemotherapy. Vincristine was administered at 0.4 mg/m2/1/day by continuous infusion (CI), vinblastine at 1.7 mg/M2/1/day by CI, and vindesine at 1.2 mg/M2/1/day by CI or intermittent bolus (IB) over 5 days. The courses were administered at 2-week intervals for vincristine and 3-week intervals for vinblastine and vindesine. Ninety-nine patients were evaluable for response. The 15 patients treated with vincristine had no objective response. Of 23 patients treated with vinblastine, there were 2 complete responses (9%) and 5 partial responses (22%). Of 31 patients treated with CI vindesine, there were 6 partial responses (19%). Of 30 patients treated with IB vindesine, there were 5 partial responses (17%). The median duration of disease control was 13 weeks (range, 8-140+) for vinblastine, 18 weeks (range, 8-34) for CI vindesine, and 20 weeks (range, 12-47) for IB vindesine. These data illustrate that vinblastine (CI) and vindesine (CI or IB) have significant antitumor activity in patients with refractory metastatic breast carcinoma and that vincristine has not antitumor activity in similar patients.

Adult↗
PubMed1985

Immune recovery following allogeneic bone marrow transplantation.

A total of 144 evaluations of cell surface markers and cellular immune functions were carried out in 57 patients undergoing allogeneic bone marrow transplantation for acute leukemia in remission and relapse and for aplastic anemia. The periods tested were pretransplant, and 1-3, 4-6, 7-12 and more than 12 months posttransplant. The determination consisted of lymphocyte counts; lymphocyte surface marking using OKT3, OKT4, and OKT8 antibodies; and determination of adherent cells, lysozymes and antibody dependent cellular cytotoxicity (ADCC) against chicken red blood cells, human red blood cells, and CEM cells. Natural killer cells were determined against K562 target cells. Lymphoblastic responses were tested after stimulation with pokeweed mitogen (PWM), concanavalin-A (Con-A), and phytohemagglutinin (PHA). We found that the progression in the leukemic state (first remission, second remission, and relapse), prior to transplantation was paralleled by a decrease in T4 lymphocytes (976/microliter +/- 462; 411/microliter +/- 222; 372/microliter +/- 419; P = .04). There was a lack of helper cells and an inverted T4:T8 ratio beyond one year posttransplant independent of graft-versus-host disease status. Lymphocyte functions persisted to be depressed for more than one year. We found a direct correlation of T4 helper cells and an inverse correlation of T8 suppressor cells with lymphoblastic responses to mitogens. It is hoped that the longitudinal evaluations of immune functions after allogeneic bone marrow transplantation, and the characterization of the immune defects seen may lead to better immunorestorative treatments.

Adolescent↗
PubMedDate not supplied

Hydroxyurea did not enhance the clinical response to vinblastine in patients with anthracycline-resistant metastatic breast cancer.

BACKGROUND: Vinblastine is commonly used in metastatic breast cancer after anthracycline failure. The response rate to vinblastine is approximately 20%, with short duration of response. In vitro studies have shown that the addition of hydroxyurea resulted in increased accumulation of vinblastine in tumor cells and in loss of double minutes. We evaluated the combination of vinblastine and hydroxyurea in patients with anthracycline-resistant metastatic breast cancer. PATIENTS AND METHODS: Fourteen assessable patients with metastatic breast cancer were entered in the study. All patients had progressed on anthracyclines or progressed within 8 months of stopping anthracyclines. Patients received hydroxyurea (500 mg orally) every Monday, Wednesday and Friday starting one week before the first course of chemotherapy and continuing throughout treatment until disease progression. Vinblastine (6 mg/m2) was given intravenously every 21 days, RESULTS: The median number of courses for vinblastine was 3.5 (range, 1-6). Three patients had partial responses in soft tissue metastases (21%). Four patients had stable disease. Four patients had > grade 2 neutropenia, and 1 patient had grade 4 thrombocytopenia. There were 2 cases of grade 3 constipation, 2 of grade 3 nausea, and 1 each of grade 2 neuropathy and myalgia. There was no treatment-related mortality. CONCLUSIONS: Low-dose hydroxyurea in combination with vinblastine has a 21% response rate in metastatic breast cancer after anthracycline failure. Toxicity was mild and generally reversible. At the adopted dose schedule of hydroxyurea, the antitumor activity of vinblastine in anthracycline-resistant metastatic breast cancer did not appear to be enhanced.

Adult↗