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Biomedical subjects

D Tuck

Publications and source records attributed to D Tuck.

18 recordsLinked to original sources
PubMed1998

Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma.

PURPOSE: To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS: Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. RESULTS: Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. CONCLUSION: Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A system for automated procedure documentation.

Quantitative information regarding competency in performing procedures is invaluable in attesting to a house officer's abilities when assessments need to be made. Thus, the means by which procedures, proficiency, and experience can be recorded and organized in an automated fashion need not be any further away than the nearest micro-computer. The procedure documenting system (PDS) automates the documenting of procedures and quantitative information pertaining to these procedures, and shortens the time demanded of the house officer to document procedures from a mean of 5.5 to 1.9 min. This paper is a description of the work done to automate the recording of procedures performed by housestaff at a teaching hospital and the acceptance by housestaff. This computer program takes the specific information and places it into a specialized database so that house officers can have detailed documentation attesting to their proficiency in various procedures. In addition, the program director can access the database to document the quantity of procedures to which an individual house officer has attained competence.

Automation↗
PubMed1994

Pancytopenia in allogeneic marrow transplant recipients: role of cytomegalovirus.

We describe the clinical course of three cytomegalovirus-antibody-positive allogeneic marrow graft recipients who developed progressive pancytopenia during the third month post-transplant. Bone marrow biopsy cores were hypocellular without evidence of disease recurrence. Haemopoietic progenitor assays demonstrated a decrease of all assayable progenitors. Cytomegalovirus was identified from the blood and urine of all three patients. However, none of the patients developed other manifestations of cytomegalovirus infection such as pneumonitis, hepatitis and enteritis. The therapeutic use of ganciclovir and intravenous immunoglobulins resulted in prompt resolution of both viraemia and viruria in all three patients, and of pancytopenia in two patients.

Adult↗
PubMed1993

Expression of membrane-bound burst-promoting activity is mediated by allogeneic effector cells.

To investigate whether "self" and "non-self" recognition processes are involved in murine erythropoiesis, the expression of membrane-bound burst-promoting activity (mBPA) was determined for B lymphocytes purified from spleens of CF-1, C57 BL/6J, B6021-7115, and CAF-1J mice using syngeneic and allogeneic bone marrow cultures. Addition of B lymphocyte conditioned medium (LCM), shed membrane-derived vesicles, or intact plasma membranes prepared from syngeneic murine cells stimulated erythroid burst-forming unit (BFU-E) proliferation by two- to three-fold above control levels. BFU-E proliferation was increased by six- to eight-fold, however, when LCM, shed membrane vesicles, or plasma membranes purified from allogenic B lymphocytes were used as sources of growth-stimulatory activity. Bioactivity was immunoprecipitated from detergent extracts of membranes purified from both allogeneic and syngeneic lymphocytes with a monoclonal antibody that specifically recognizes mBPA, suggesting that the factors expressed by these cells share antigenic determinants. The results indicate that allogeneic effector cells are a more potent source of mBPA-like molecules than are syngeneic cells, suggesting that immune mechanisms may be involved in inducing erythroid growth factor expression at the B cell surface.

Animals↗
PubMed1988

Immunologic enhancement of B16 melanoma growth.

In certain experimental tumor models, tumor growth is less pronounced in immune deficient animals. Characteristically, tumors such as the murine B16 melanoma and Lewis lung carcinoma (3LL) are weakly antigenic. We proposed that with such tumors that are weakly antigenic, growth is enhanced by T-cell factors. Young mice were inoculated with irradiated B16 cells in complete Freunds adjuvant (CFA) on three occasions, each separated by 2 weeks. Specific antibody (IgG) to B16 membrane antigens was detected by an enzyme-linked immunosorbent assay (ELISA) after the first injection, and it continued to rise for 6 weeks. B16 growth was compared in 20 mice that had received irradiated B16 in CFA or CFA alone by the same schedule previously. Despite the previous sensitization, the rates of tumor appearance and growth were similar. In an additional experiment involving 23 mice that had received B16 immunization, the period of time in which a palpable tumor developed after the injection of viable B16 cells did not correlate with anti-B16 antibody level. It appeared that detectable antibody to B16 antigens was of little consequence. To explain why B16 primary growth and metastases were reduced in immune deficient hosts, we proposed that lymphocytes might enhance tumor growth. To demonstrate this, splenic lymphocytes from tumor-bearing (B16 or 3LL) or control mice were injected with B16 cells into young, immune competent hosts. Tumors (B16) developed earlier and growth was more rapid in mice that received spleen cells from tumor-bearing (B16) mice. Subsequent cell depletion experiments to determine the mediator of tumor enhancement implicated a T-cell fraction that was neither of T-helper nor T-suppressor cell type phenotypically. Immune deficiency states that are associated with dysfunction of those cells that account for tumor enhancement might explain the reduced tumor aggressiveness that is observed frequently in these conditions.

Animals↗
PubMed1971

Relationship between plasma level and therapeutic effect of nortriptyline.

The relationship between plasma concentration of nortriptyline and therapeutic effect after two weeks' treatment with the drug was investigated in 29 psychiatric inpatients. Endogenous depression was diagnosed in all patients. Amelioration of depressive symptoms was estimated as reduction in score on a rating scale, based on a psychiatric interview. Amelioration was not correlated to the patient's sex or age. There was a curved relationship between plasma level of nortriptyline and therapeutic effect. Amelioration was most pronounced in the intermediate plasma level range (50-139 ng nortriptyline/ml plasma) and was slight both at lower and at higher plasma levels. This type of relationship may be due to the dual action of tricyclic antidepressants which has been found in animal experiments. On larger dosages a phenothiazine-like blockade of the monoaminergic receptor is added to the blockade of monoamine reuptake thought to be related to the antidepressant action of the drugs.THIS STUDY THUS SUGGESTS TWO POSSIBLE REASONS FOR A THERAPEUTIC FAILURE WITH NORTRIPTYLINE: a too low or a too high plasma level. The large individual variation in the pharmacokinetics of the tricyclic antidepressants makes prediction of plasma level from dosage in a given individual virtually impossible without knowledge of rate of elimination and apparent volume of distribution. Hence monitoring plasma levels may be a way to increase the efficacy of treatment with these drugs.

Adult↗
PubMed1970

Correlation of subjective side effects with plasma concentrations of nortriptyline.

Plasma levels of tricyclic antidepressant drugs vary considerably between individuals receiving the same amount of drug. The bearing of this variation on the occurrence of subjective side effects was investigated in 40 psychiatric inpatients with depressive disorders. Plasma levels were determined before and during four weeks of treatment with nortriptyline 50 mg. three times a day and patients were rated for subjective side effects, the assessors being unaware of the plasma levels of the drug.Plasma levels varied widely between individual patients, but in any given patient the plasma level tended to be constant over a period of time. The side effects of nortriptyline diminished significantly with time and were in most cases absent during the fourth week of treatment. There was a significant positive correlation between plasma level of nortriptyline and subjective side effects.The steady-state plasma level of a drug which is metabolized is usually a more important determinant for its effect than dosage, since it reflects the amount of drug available for biological action. Very high plasma levels of nortriptyline should presumably be avoided, since there is no evidence that they are needed for therapeutic effect and they are potentially harmful.

Adult↗
PubMedDate not supplied

Factors affecting recovery after peripheral blood stem cell transplantation.

To determine the factors that might be involved in successful engraftment following administration of autologous peripheral blood stem cells (PBSC) obtained by leukapheresis to replace bone marrow after ablation therapy for malignant disease, four patients were examined in detail. One who had had pelvic radiation as well as chemotherapy had a prolonged, gradual but complete recovery. One who received granulocyte-macrophage-colony stimulating factor (GM-CSF) following PBSC infusion showed a rapid recovery phase, but developed high fever (culture negative) associated with arrested hematopoiesis and died with central nervous system (CNS) symptoms after 120 days. Two other patients recovered without major incident. Concentration of PBSC was analyzed by: (1) approximation by counting mononuclear cells (MNC); (2) CD34 cells by flow cytometric analysis; and (3) colony forming units-granulocyte macrophage (CFU-GM) by colony formation in microtiter plates. The time to BM recovery (retics > 1.0 percent, neutrophils > 500 per cumm, platelets > 50,000 per cumm) was determined by following daily counts. Engraftment appeared to depend upon an adequate minimum dose of PBSC, but ultimate recovery of the patient seemed to be determined by ancillary factors, especially CNS infection. These patients illustrate that while rapidity of bone marrow (BM) recovery may be related to PBSC dose, other factors, particularly infection, influence patient outcome.

Adult↗