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T Garrett

Publications and source records attributed to T Garrett.

13 recordsLinked to original sources
PubMed2001

Reduction of paclitaxel-induced peripheral neuropathy with glutamine.

PURPOSE: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose paclitaxel. EXPERIMENTAL DESIGN: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m(2) given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. RESULTS: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P < 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. CONCLUSIONS: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.

Activities of Daily Living↗
PubMed1998

Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy. PATIENTS AND METHODS: Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy. RESULTS: High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered. CONCLUSION: These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.

Adult↗
PubMed1998

Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.

A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity.

Adult↗
PubMed1990

Attitudes to the training of general medical practitioners in Nigeria.

Nigeria has pioneered a vocational training programme for general medical practitioners. The first major evaluation and review of the curriculum took place in July 1988 when over 50 trainees, supervisors and faculty board members attended a conference at Ibadan University. The opportunity was taken to assess by questionnaire the views of the participants on a range of issues related to health care in Nigeria and of the training and supervision of general medical practitioners. Sixty-six per cent of potential respondents provided completed questionnaires. A large proportion of respondents felt the need for some revisions in the curriculum and for a greater emphasis on small group training. The results indicated scepticism about the role of high technology medicine and private medical practice in meeting the health needs of Nigerians. There were some differences between the trainees and their supervisors and faculty board members in the responses obtained. The programme in Nigeria and the attitudes of those taking part demonstrate a vigorous and visionary approach to health care. It is hoped that this experience will be a useful and important example of what can be achieved in a country with potential for development.

Attitude of Health Personnel↗
PubMed1987

Comparison of outcome of low-risk labour in an isolated general practice maternity unit and a specialist maternity hospital.

The outcome of labour of 185 low-risk pregnancies at an isolated general practitioner maternity unit was compared with that for 185 comparable low-risk pregnancies at a specialist maternity hospital. No difference was found in mode of delivery or in the proportion of women requiring no analgesia, although significantly more women in the general practice group received analgesia beyond nitrous oxide. There was a significantly higher level of intervention in labour in the maternity hospital group in the form of fetal monitoring and augmentation of labour. The duration of first stage of labour was longer and meconium staining less frequent in the general practice group. Fourteen (7.6%) of the general practice group were transferred in labour to the specialist unit.The results suggest that where considerations for selection of low-risk pregnancy permit, the general practice maternity unit can provide a distinctive style of intrapartum care with minimum intervention.

Delivery Rooms↗
PubMed1987

Outcome of women booked into an isolated general practice maternity unit over eight years.

The outcome of pregnancy of 1303 women admitted for delivery (including those transferred after admission) at an isolated general practitioner maternity unit over the period 1978-85 was studied. The outcome following change of booking before admission was also assessed for the years 1982-85. The crude perinatal mortality rate was 1.5 per 1000 for all admissions between 1978 and 1985. Of the women admitted in 1978-85 7.4% were transferred after admission while for those booked at the unit in 1982-85 11.3% had their place of booking changed. A higher proportion of nulliparous women than multiparous women were transferred or had their place of booking changed. The main reasons for transfer after admission were delay in the first stage of labour (21.9%), spontaneous rupture of membranes not in labour (16.7%) and hypertension (15.6%), and for change of booking postmaturity (26.9%) and hypertension (16.4%).Sufficient information concerning risk of transfer and change of booking may now be available from studies of isolated general practice maternity units for pregnant women at low risk to make an informed choice of place for delivery.

Delivery Rooms↗
PubMed1980

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts.

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null-type ALL). Leukemic blasts of 4 children formed E-rosettes. These E-rosette-forming blasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2--76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9--42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T-cell ALL. Complement receptors were detected on 9--70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T-cell ALL and in children with null-type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T-cell leukemias with regard to prognosis and the response to therapy.

Adult↗
PubMed1980

Studies in acute leukemia. II. Chemotaxis of leukemic blasts from patients with acute nonlymphoid leukemia: its relationship with IgG Fc receptors and role of surface-bound immunoglobulin.

Leukemic blasts from patients with acute myeloblastic and acute monocytic leukemia were studied for their chemotaxis towards casein- or endotoxin-activated serum as well as for the presence of Fc receptors and surface immunoglobulins. Leukemic blasts from patients with acute myeloblastic leukemia lacked both Fc receptors and surface immunoglobulin and did not migrate towards chemoattractants. Leukemic blasts from patients with acute monocytic leukemia, however, demonstrated heterogeneity with regard to Fc receptors, surface immunoglobulins and chemotaxis, and could be divided into three groups: in group I, leukemic blasts which lacked both Fc receptors and surface immunoglobulin moved poorly; in group II, large proportions of leukemic blasts and Fc receptors but lacked surface immunoglobulins. These blasts migrated well towards the chemoattractants, and in group III, leukemic blasts which had both Fc receptors and surface immunoglobulins lacked chemotactic property. A correlation between the presence or absence of Fc receptors and chemotaxis was observed. In group III, lack of blast cell migration appears to be due to passive binding of IgG via the Fc receptors.

Acute Disease↗
PubMed1979

Studies in acute leukemia. I. Antibody-dependent and spontaneous cellular cytotoxicity by leukemic blasts from patients with acute nonlymphoid leukemia.

Leukemic blasts from patients with acute nonlymphoid leukemia were examined for the presence of Ig, receptors for IgGFc, and for their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against chicken red blood cells (RBC) coated with IgG and spontaneous cell-mediated cytotoxicity (SCMC) against cells of K562 cell line. Leukemic blasts from acute myeloblastic leukemia (AML) patients lacked both Fc receptors and Ig on their surface, had no SCMC activity and majority, but not all of them, lacked ADCC activity. Leukemic blasts from patients with acute monocytic leukemia (AMOL) had Fc receptors, and 50% had IgG on their surface. IgG was cytophilic and appeared not to be directed against cell-surface antigens. This antibody did not interfere with the ADCC activity of leukemic cells. Leukemic blasts from majority of patients with AMOL mediated ADCC, but had no SCMC activity. An association between ADCC and presence of Fc receptor was observed.

Adult↗
PubMed1976

Reported consequences of decriminalization of consensual adult homosexuality in seven American states.

This article reports results of a survey of police officials, prosecuting attorneys, and members of homosexual groups in the seven states that had decriminalized private homosexual behavior between consenting adults. Despite the dire predictions of many, the responses indicate that, among other things, decriminalization has had no effect on the involvement of homosexuals with minors, the use of force by homosexuals, or the amount of private homosexual behavior. Additionally, decriminalization reportedly eased somewhat the problems of the homosexual community and allowed the police to devote more time to the investigation of what generally are regarded as more serious criminal offenses.

Adult↗