PubMed Health⌕ Search

Biomedical subjects

F M Stewart

Publications and source records attributed to F M Stewart.

At least 19 recordsLinked to original sources
PubMed1997

Late regression of the dilated site after coronary angioplasty: a 5-year quantitative angiographic study.

BACKGROUND: Limited data are available on the changes that occur at the dilated site late after coronary angioplasty. The aim of this study was to evaluate with quantitative angiography the natural history of changes that occur in the dilated segment between "early" (approximately 6 months) and "late" (approximately 5 years) follow-up after angioplasty. METHODS AND RESULTS: Of 127 consecutive patients (174 lesions) with successful angioplasty, 125 underwent early angiography. Three patients subsequently died, and 24 underwent revascularization surgery or repeated angioplasty, giving a study-eligible population of 98 patients. Quantitative angiographic analysis was performed before and immediately after angioplasty and at early and late follow-up in the study population of 84 patients (115 lesions), which was 86% of study-eligible patients. Mean lesion diameter stenosis decreased from 36.3+/-14.2% at early to 29.6+/-13.5% at late follow-up (P<.0001). No lesion developed late restenosis by the 50% diameter loss criterion. Late regression was related to stenosis severity at early angiography (r=-.58, P<.001). Subgroups at early angiography of 40% to 49% stenosis and > or = 50% stenosis showed significant regression at late angiography. CONCLUSIONS: Lesion regression at the dilated site is common late after angioplasty. The more severe a stenosis is at early angiography, the more likely the chance that there will be late regression. A strategy of watchful waiting may be appropriate for patients with restenotic lesions of borderline severity.

Adult↗
PubMed1997

Cytokine-facilitated transduction leads to low-level engraftment in nonablated hosts.

Using a murine bone marrow transplantation model, we evaluated the long-term engraftment of retrovirally transduced bone marrow cells in nonmyeloablated hosts. Male bone marrow was stimulated in a cocktail of interleukin-3 (IL-3), IL-6, IL-11, and stem cell factor (SCF) for 48 hours, then cocultured on the retroviral producer line MDR18.1 for an additional 24 hours. Functional transduction of hematopoietic progenitors was detected in vitro by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of multiple drug resistance 1 (MDR1) mRNA from high proliferative potential-colony forming cell (HPP-CFC) colonies. After retroviral transduction, male bone marrow cells were injected into nonablated female mice. Transplant recipients received three TAXOL (Bristol-Myers, Princeton, NJ) injections (10 mg/kg) over a 14-month period. Transplant recipient tissues were analyzed by Southern blot and fluorescence in situ hybridization for Y-chromosome-specific sequences and showed donor cell engraftment of approximately 9%. However, polymerase chain reaction amplification of DNAs from bone marrow, spleen, and peripheral blood showed no evidence of the transduced MDR1 gene. RT-PCR analysis of total bone marrow RNA showed that transcripts from the MDR1 gene were present in a fraction of the engrafted donor cells. These data show functional transfer of the MDR1 gene into nonmyeloablated murine hosts. However, the high rates of in vitro transduction into HPP-CFC, coupled with the low in vivo engraftment rate of donor cells containing the MDR1 gene, suggest that the majority of stem cells that incorporated the retroviral construct did not stably engraft in the host. Based on additional studies that indicate that ex vivo culture of bone marrow induces an engraftment defect concomitantly with progression of cells through S phase, we propose that the cell cycle transit required for proviral integration reduces or impairs the ability of transduced cells to stably engraft.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

The population genetics of antibiotic resistance.

Mathematical models are used to ascertain the relationship between the incidence of antibiotic treatment and the frequency of resistant bacteria in the commensal flora of human hosts, as well as the rates at which these frequencies would decline following a cessation of antibiotic use. Recent studies of the population biology of plasmid-encoded and chromosomal antibiotic resistance are reviewed for estimates of the parameters of these models and to evaluate other factors contributing to the fate of antibiotic-resistant bacteria in human hosts. The implications of these theoretical and empirical results to the future of antibacterial chemotherapy are discussed.

Anti-Bacterial Agents↗
PubMed1997

Adoptive immunotherapy.

Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive immunotherapy has been used for relapses after allogeneic bone marrow transplantation, and it has been particularly effective for chronic myeloid leukemia. Adoptive immunotherapy also has been used for Epstein-Barr virus-related lymphomas developing after allogeneic marrow transplantations. Cellular therapy, including the infusion of tumor-reactive immune cells, has been used to mediate response of established solid tumors. This has been used for therapeutic benefit for renal cell carcinoma, melanoma, lung cancer, and breast cancer. Current research is focusing on reducing the toxicity of these approaches as well as further defining the appropriate target tissue.

Animals↗
PubMed1997

Clinical impact of chemotherapy dose escalation in patients with hematologic malignancies and solid tumors.

PURPOSE: To review published controlled clinical trials examining the benefit of escalated chemotherapy in patients with hematologic and solid malignancies. METHODS: Studies were obtained by searching Medline and CancerLit and by review of bibliographies of published trials. We reviewed studies that examined dose-intense (DI) chemotherapy alone, in combination with hematopoietic colony-stimulating factors (CSFs), or high-dose therapy (HDT) with autologous bone marrow support (ABMT). RESULTS: DI therapy without CSF or ABMT has not been shown to improve overall outcome in any tumor except consolidative therapy of acute myelogenous leukemia (AML). In solid tumors, many published studies suggest that less than standard-intensity chemotherapy is suboptimal, but few studies that examined higher compared with standard-dose therapy have shown a significant difference in outcome. No studies have convincingly demonstrated improved overall survival (OS) with DI therapy with CSF support. The use of HDT with ABMT has been shown to improve survival in multiple myeloma (MM), as well as relapsed intermediate- and high-grade non-Hodgkin's lymphoma (NHL). High-dose chemotherapy with ABMT is promising in patients with metastatic breast cancer (MBC), but it should not yet be considered a standard approach for these patients. CONCLUSION: DI chemotherapy is an acceptable and standard therapeutic maneuver for patients with AML in first remission, MM, and relapsed aggressive NHL. In solid tumors, the use of DI chemotherapy either alone or with cytokine support has not been shown to improve outcome and should not be considered standard therapy. Current randomized trials should provide definitive answers about the role of DI therapy in solid tumors.

Antineoplastic Agents↗
PubMed1997

Stem cell transplantation in the normal nonmyeloablated host: relationship between cell dose, schedule, and engraftment.

In previous studies we have shown high rates of stable engraftment when 40 million male BALB/c cells were infused intravenously daily for 5 days (a total of 200 million cells) to normal nonmyeloablated female hosts. The present studies evaluate engraftment of male BALB/c bone marrow cells in female host marrow, spleen, and thymus 20-25 weeks after transplantation using varying cell dosages within a 5-day schedule. Engraftment in recipient mice was assessed by detection of male specific sequence in recipient DNA from each organ. When 40 million cells were given per daily injection for 1, 2, 3, 4, or 5 days, engraftment percentages in host marrow were 11 +/- 0.83, 20 +/- 2.0, 23 +/- 2.5, 32 +/- 6.3, and 39% +/- 5.7 (+/- standard error of mean), respectively, yielding engraftment percentages per million cells infused of 0.28, 0.25, 0.19, 0.20, and 0.20%, respectively. When levels of 2.5, 5, 10, 20, or 40 million cells were injected 5 times over a 5-day schedule into normal BALB/c female hosts, progressively increasing levels of engraftment from 3 +/- 0.6 to 39% +/- 5.7 were seen in host marrow. Highest levels of engraftment per million cells injected were obtained on days 1 and 2 of a 5-day schedule and with a level of 10 million cells given daily over 5 days. Engraftment profiles varied with spleen and thymus and percent engraftment was generally lower than for marrow. The present work indicates that regardless of cell level infused or number of infusions, rates of engraftment observed in marrow approached or exceeded the highest rates of engraftment estimated by theoretical calculations based on replacing host cells ("replacement model") or adding to host cells ("incremental model"). Engraftment in spleen and thymus was lower, but also at times approached or exceeded theoretical maxima. These data show extraordinary levels of engraftment in normal hosts, suggesting that rates in this competitive model are superior to those seen in irradiated hosts; alternatively, there may be selective repression of host stem cell proliferation and differentiation.

Animals↗
PubMed1997

Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells.

Granulocyte colony-stimulating factor (G-CSF) has been used to improve granulocyte count in chronic neutropenia and myelodysplasia, to minimize the incidence and duration of neutropenia during conventional chemotherapy, and to mobilize peripheral blood stem cells prior to leukapheresis for use in autologous and allogeneic marrow transplantation. The most common toxicity is bone pain, and other reactions such as inflammation at the site of injection have also occurred. In patients with chronic neutropenia, splenomegaly has been described with long-term use, and extramedullary hematopoiesis has also been reported. However, thus far, no life-threatening sequelae of these effects are found in the literature. We now describe a case of spontaneous splenic rupture four days following a six-day course of G-CSF therapy in an allogeneic donor of peripheral blood stem cells.

Acute Disease↗
PubMed1996

Sex differences in case fatality before and after admission to hospital after acute cardiac events: analysis of community based coronary heart disease register.

OBJECTIVE: To determine whether the reported higher case fatality in hospital after an acute cardiac event in women can be explained by sex differences in mortality before admission and in baseline risk factors. DESIGN: Analyses of data from a community based coronary heart disease register. SETTING: Auckland region, New Zealand. SUBJECTS: 5106 patients aged 25-64 years with an acute cardiac event leading to coronary death or definite myocardial infarction within 28 days of onset, occurring between 1986 and 1992. MAIN OUTCOME MEASURES: Case fatality before admission, 28 day case fatality for patients in hospital, and total case fatality after an acute cardiac event. RESULTS: Despite a more unfavourable risk profile women tended to have lower case fatality before admission than men (crude odds ratio 0.88; 95% confidence interval 0.77 to 1.02). Adjustment for age, living arrangements, smoking, medical history, and treatment increased the effect of sex (0.72; 0.60 to 0.86). After admission to hospital, women had a higher case fatality than men (1.76; 1.43 to 2.17), but after adjustment for confounders this was reduced to 1.18 (0.89 to 1.58). Total case fatality 28 days after an acute cardiac event showed no significant difference between men and women (0.85; 0.70 to 1.02) CONCLUSIONS: The higher case fatality after an acute cardiac event in women admitted to hospital is largely explained by differences in living status, history, and medical treatment and is balanced by a lower case fatality before admission.

Adult↗
PubMed1996

Relationships between heavy metal and metallothionein concentrations in lesser black-backed gulls, Larus fuscus, and Cory's shearwater, Calonectris diomedea.

Metallothionein, cadmium, zinc, copper, and mercury concentrations were measured in adult lesser black-backed gulls, Larus fuscus; and metallothionein, cadmium, zinc, and copper concentrations were measured in fledgling Cory's shearwaters, Calonectris diomedea. In gulls, metallothionein was positively correlated with cadmium (kidney r = 0.83, liver r = 0.46), zinc (kidney r = 0.46, liver r = 0.37), and copper (kidney r = 0.28, liver r = 0.34). Mercury levels in lesser black-backed gulls showed no correlations with metallothionein or with any other metal. In shearwaters metallothionein was positively correlated with cadmium in the kidney (r = 0.41) but not in liver, zinc in kidney (r = 0.43) and liver (r = 0.52), and copper in kidney (r = 0.55) but not in liver. Cadmium levels were the most important factor determining tissue metallothionein concentrations in adult lesser black-backed gulls demonstrating the role of metallothionein in heavy metal detoxification. In fledgling Cory's shearwaters, the most important factor in determining metallothionein concentrations in kidney was copper concentrations, and in liver, zinc concentrations. During the latter phases of chick growth high levels of zinc are required for feather development, and at this time the binding of cadmium may be masked by the presence of a large amount of zinc- and copper-bound metallothionein. These results illustrate disparate roles of metallothionein, the levels of which will be in a state of flux both seasonally and annually.

Animals↗
PubMed1996

The intrinsic rate of increase of HIV/AIDS: epidemiological and evolutionary implications.

A method derived from demographic theory is presented for modeling the epidemiology of an infectious disease. For long-term infections, this method better accounts for host variation in survival and transmission rates than classical compartment models. Examples of the applications of this method focus on a single long-term infectious disease, HIV/AIDS. The method is employed to examine (1) how changes in transmission rates during different stages of infection affect the rate of spread of HIV/AIDS both in wholly susceptible populations and in populations where the number of potential hosts is limited, (2) the way the relative frequencies of the different stages of infection vary over time, (3) how the rate at which the epidemic is growing (or diminishing) affects the fraction of HIV-infected individuals who manifest the symptoms of AIDS, (4) the effect of treatment on the rate of spread of HIV, and (5) the potential effects of natural selection on the virulence of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The nature and prevalence of memory disorder late after stroke.

This study aimed to investigate the incidence and nature of memory impairment late after stroke. Out of 193 patients between 12 to 36 months post-cerebrovascular accident contacted in a postal survey, 113 replied that they had experienced memory impairment following the stroke. Seventy of these patients were assessed on an adapted version of the Rivermead Behavioural Memory Test, Warrington's Recognition Memory Test for words and faces, and an every day memory questionnaire. The Token Test and the Benton Facial Recognition Test were also administered as measures of language and visuoperceptual processing. Thirty-five of the patients were impaired on one or more of the memory measures. Of these, 16 showed no evidence of dysphasia or visuoperceptual impairment. The 16 cases of selective memory impairment typically had mild to moderate deficits, and only three were impaired across all three tests. The results suggest that memory impairment following stroke does not necessarily involve general memory impairment. The evidence for material-specific memory deficits was much weaker.

Adult↗
PubMed1996

Adaptation to cognitive deficit? An exploration of apparent dissociations between everyday memory and test performance late after stroke.

It is widely believed that spontaneous improvements in functioning late after brain damage are due to processes of adaptation to permanent cognitive deficits. Reports of everyday memory and the pattern of performance on memory tests were investigated in 70 patients more than a year after a stroke. Contrary to the adaptation hypothesis, performance on simulations of everyday tasks (Rivermead Behavioural Memory Test) correlated strongly with performance on a test where there was little scope for compensatory strategies (forced-choice recognition memory for words). In 12 cases, initial assessment with the EMQ20 questionnaire suggested few cognitive failures in everyday life despite poor test performance. However, where further investigation was possible, it seemed that unreliability of measures or subtle everyday effects of non-verbal memory impairment could explain the apparent discrepancies. In addition, patients who did poorly on tests were not reported to make frequent use of memory aids. Adaptation to deficit does not therefore appear to be a major influence on everyday memory performance late after stroke, but it may have subtle effects or may be important in other areas of functioning. Implications for clinical memory assessment are discussed.

Activities of Daily Living↗
PubMed1996

Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients.

Human lymphoematopoietic stem cells engraft in irradiated immunodeficient mice that are homozygous for the severe combined immunodeficiency (scid) mutation. Engraftment levels in C.B-17-scid/scid mice, however, have been low and transient, decreasing the utility of this model for investigation of the development potential and function of human stem cells. In the present study, we have used NOD/LtSz-scid/scid mice as recipients and human cord blood as a source of donor stem cells. Our results demonstrate that NOD/LtSz-scid/scid mice support approximately fivefold higher levels of human stem cell marrow engraftment than do C.B-17-scid/scid mice. Human CD34+ cells are present in the marrow of recipient mice, and the engrafted cells readily peripheralize to the circulation of the host. Terminal differentiation of the stem and progenitor cells into mature progeny is limited. Using a multiple-day injection protocol developed in mice, which allows engraftment of stem cells between congenic mice in the absence of irradiation preconditioning, we observed high levels of human cell engraftment in unirradiated NOD/LtSz-scid/scid recipients after three or five consecutive-day injections. These results demonstrate that NOD/LtSz-scid/scid mice support high levels of human stem cell engraftment and that xenogeneic lymphohematopoietic stem cells can engraft in unirradiated hosts without the need for ablative reconditioning. This model will be useful for the in vivo investigation of human stem cells and for the preclinical analysis of human stem cells for transplantation.

Animals↗
PubMed1995

Cytokines in stem cell transplantation.

The use of cytokines in stem cell transplantation is still in the early stages of development. Efficacy has not been established consistently at the present time. When cytokines are employed in the treatment setting, they should be employed in a study setting evaluating whether there has been real patient benefit-palliation without compromise of therapeutic outcome or, preferably, a survival advantage. Cost effectiveness has not been established and, in any case it should not be a consideration until therapeutic efficacy has been established. The determination of various biologic parameters on cells such as cytokine receptors may permit more precise use of HGFs. In some cases there probably are subsets of patients who are benefited, while there are subsets who are harmed. The challenge of the future is to define these subsets.

Bone Marrow Transplantation↗
PubMed1995

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation.

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.

Antigens, CD↗
PubMed1995

Disconnected.

Explore the source record for details and available documents.

Clinical Trials as Topic↗