Search PubMed⌕ Search

Biomedical subjects

D A Stewart

Publications and source records attributed to D A Stewart.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antiangiogenic gene therapy for cancer via systemic administration of adenoviral vectors expressing secretable endostatin.

A growing number of antiangiogenesis strategies have been investigated for the treatment of cancer and other angiogenesis-dependent diseases. One of the most promising strategies is to systemically administer one or more antiangiogenic proteins frequently enough to achieve a sufficient long-term steady state level of the protein(s) to achieve the maximum beneficial effect. However, the utility of this strategy is limited because of many technical difficulties, including obtaining both the quantity and quality of the protein(s) necessary for optimal therapeutic benefit. To overcome these difficulties, we hypothesized that a single administration of a replication-defective adenoviral vector expressing a secretable antiangiogenic protein could achieve an optimal long-term systemic concentration. We constructed a recombinant adenoviral vector, Av3mEndo, which encodes a secretable form of murine endostatin. We demonstrated secretion of endostatin from several cell lines transduced with Av3mEndo. Partially purified endostatin secreted from Av3mEndo-transduced mammalian cells was shown to potently inhibit endothelial cell migration in vitro. A single intravenous administration of Av3mEndo in mice was shown to result in (1) prolonged and elevated levels of circulating endostatin, (2) partial inhibition of VEGF-induced angiogenesis in a VEGF implant angiogenesis model, and (3) prolonged survival and in 25% of mice the complete prevention of tumor growth in a prophylactic human colon/liver metastasis xenograft murine model. These results support our contention that adenoviral vector-mediated expression of an antiangiogenic protein(s) represents an attractive therapeutic approach to cancer and other angiogenesis-dependent diseases.

Adenoviridae↗
PubMed2000

The CD34+90+ cell dose does not predict early engraftment of autologous blood stem cells as well as the total CD34+ cell dose.

CD90 or Thy-1 is an antigen co-expressed with CD34+ on putative immature hematopoietic stem cells. Peak mobilization of CD34+90+ cells into the blood occurs a few days earlier than peak mobilization of total CD34+ cells. Because it is not known which cell type best correlates with engraftment, the optimal timing of apheresis remains unclear. The purpose of the study was to determine if the CD34+90+ cell dose predicts engraftment of autologous blood stem cells independent of the total CD34+ cell dose/kg, the dose of other CD34+ cell subsets (CD34+33-, CD34+38-, CD34+41+), or various clinical factors. Data were analyzed on 125 consecutive patients ranging in age from 19 to 66 years (median 46) who underwent autologous blood stem cell transplantation (ABSCT) for breast cancer (54), lymphoma (59), or other malignancies (12). By univariate analysis, neutrophil (> or = 0.5 x 10(9)/l) and platelet (> or = 20 x 10(9)/l or > or = 100 x 10(9)/l) engraftment correlated better with the total CD34+ cell dose than with the CD34+90+ cell subset. Using Cox proportional hazards models, factors independently associated with both neutrophil engraftment (> or = 0.5 x 10(9)/l) and platelet engraftment (> or = 20 x 10(9)/l and > or = 100 x 10(9)/l) were higher total CD34+ dose/kg and high-dose regimen (melphalan-containing slower than other regimens). In conclusion, the total CD34+ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34+ subset, including CD34+90+ cells. Apheresis should continue to be timed according to peak CD34+ levels.

Adult↗
PubMed2000

A comparison of inpatient and outpatient ASCT.

Outpatient high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to be feasible in terms of physical morbidity and mortality outcomes, but few data exist on the psychosocial impact of delivering such aggressive therapy in this manner. The purpose of this observational study was to compare effects of inpatient (n = 20) and outpatient (n = 21) modes of care on physical status, psychological well-being, quality of life, personal finances and caregiver burden. Most patients were treated according to their preference for inpatient or outpatient care. Those choosing outpatient care were screened for eligibility according to established criteria for ambulatory management. Measures were taken at baseline, then at days 4-6, 12-16 and 30 post ASCT. Results showed that overall, the psychological, physical, social and financial outcomes of the outpatient ASCT group were comparable, to or better than inpatients. Factors that seem to be important for successful outpatient management are previous experience with cancer treatment, a satisfying quality of life, physical well-being, patient's preference for a particular mode of care and physical proximity to the treatment centre. The study results suggest that outpatient ASCT is an efficient, effective and acceptable form of care for motivated patients and caregivers who have the physical and psychological capability and desire to receive cancer treatment in this manner.

Adult↗
PubMed2000

Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior to high-dose melphalan and autologous stem cell transplantation.

We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) HD. DICEP re-induction and blood stem cell mobilization was used for 21 patients. Factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, B symptoms at relapse, bulk, post-ASCT radiotherapy, and DICEP re-induction therapy. Cox proportional hazards models were constructed for both event and death. DICEP and HDM were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. For all 46 patients, the projected 5 year EFS was 52% (95% CI = 38-72%) and OAS was 57% (95% CI = 40-82). Factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). Factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), > or =3 prior chemotherapy regimens (RR = 4.72, P = 0.019), and not using DICEP (RR = 7.49, P = 0.015). This study demonstrates that DICEP re-induction prior to HDM/ASCT is feasible. The preliminary data are sufficiently encouraging to warrant a multicenter phase II or a phase III trial evaluating DICEP followed by HDM/ASCT as salvage therapy for HD.

Adolescent↗
PubMed2000

Predictive factors for long-term engraftment of autologous blood stem cells.

Data from 170 consecutive patients aged 19-66 years (median age 46 years) who underwent unmanipulated autologous blood stem cell transplant (ASCT) were analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+, CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+) count on first apheresis day, or various clinical factors were associated with low blood counts 6 months post ASCT. Thirty-four patients were excluded from analysis either because of death (n = 17) or re-induction chemotherapy prior to 6 months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the remaining 136 patients, 46% had low WBC ( < 4 x 10(9)/l), 41% low platelets (<150 x 10(9)/l), and 34% low hemoglobin ( < 120 g/l) at a median of 6 months following ASCT. By Spearman's rank correlation, both the total CD34+ cell dose/kg and the PBCD34+ count correlated with 6 month blood counts better than any subset of CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both factors retained their significance in multivariate analysis, controlling for clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month blood counts following ASCT.

Adult↗
PubMed2000

Early gastric post-transplantation lymphoproliferative disorder and H pylori detection after kidney transplantation: a case report and review of the literature.

The incidence of post-transplantation lymphoproliferative disorder (PTLD) in the adult renal transplant population ranges from 0.7% to 4%. The majority of cases involve a single site and arise, on average, seven months after transplantation. Histopathology usually reveals B-cell proliferative disease and has been standardized into its own classification. Treatment modalities consist of decreased immunosuppression, eradication of Epstein-Barr virus, surgical resection, systemic chemotherapy and monoclonal antibody therapy; however, mortality remains high, typically with a short survival time. In patients who have undergone renal transplantation, approximately 10% of those with PTLDs present with gastrointestinal symptomatology and disease. Reported sites include the stomach, and small and large bowel. Very few cases of Helicobacter pylori or mucosal-associated lymphoid tissue have been described in association with PTLD. In the era of cyclosporine immunosuppression, the incidence of PTLD affecting the gastrointestinal tract may be increasing in comparison with the incidence seen with the use of older immunosuppression regimens. A case of antral PTLD and H pylori infection occurring three months after renal transplantation is presented, and the natural history and management of gastric PTLD are reviewed.

Helicobacter Infections↗
PubMed2000

Attitudes regarding vaccinations of STDs and other diseases.

The purpose of this study was to examine, among 2 groups of individuals with different risk profiles, the similarity of their attitudes towards vaccines for sexually transmitted diseases (STDs) and non-STDs. Subjects were recruited from an undergraduate psychology class at an urban university (n=518) or were participants in genital herpes vaccine trials (n=87). The participants were asked to complete a questionnaire regarding their attitudes about vaccines for selected diseases. The results of this study revealed that, in general, both groups supported vaccination for most diseases. There were differences, however, between groups regarding 3 diseases: measles, genital warts, and chlamydia. The vaccine trial participants were more likely to accept vaccines for measles and the college students were more likely to accept vaccines for chlamydia and genital warts. The results of this study suggest that negative attitudes regarding vaccination to control STDs may not be a significant barrier to use.

Adolescent↗
PubMed2000

Documenting English syntactic development in face-to-face signed communication.

The authors explored the face-to-face English competence of five students who were participating in a larger study of teachers' use of English-based signing. Using case studies, the authors report on the students' development of English-based signing at the beginning and end of their involvement in this 4-year study. Grammatical forms similar in English and American Sign Language (ASL) were initially more readily produced when tested for in English, and showed consistently higher attainment levels across all the students, than grammatical forms that are different in English and ASL. The authors found emerging English forms that could be documented (a) between prompted and imitated utterances and (b) within blocks of test items examining the same grammatical constructions. The authors conclude that teachers' concerted efforts to use English-based signing as a language of instruction enhance deaf students' English acquisition. Such signing helps build a bridge between native sign language and the development of English skills necessary for literacy.

Child↗
PubMed2000

Cochlear implants for younger children: a preliminary description of the parental decision process and outcomes.

The authors conducted a preliminary telephone interview study of a random sample of 35 parents whose children had received cochlear implants through a large-scale implant program. Parents were asked about their child's preimplant and postimplant communications skills, how they learned about implants, and how they arrived at the decision to have their child receive an implant. Results of the interviews suggest, a least for this program, that two types of decision sequences are followed. One type of parent has initial and primary contact through a medical practitioner, uses that source of information exclusively, and is motivated by a desire for a "normal" communication situation. The second type of parent learns about implants from another parent, family member, or teacher. This individual will seek other sources of information and is most often motivated by the child's lack of communication skill. Generally, from parents' perspective, language and speech rather than improved social skills or social contact are the primary benefits of the implant.

Child, Preschool↗
PubMed1999

Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens.

The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.

Adolescent↗
PubMed1999

Factors predicting engraftment of autologous blood stem cells: CD34+ subsets inferior to the total CD34+ cell dose.

Data were analyzed on 178 consecutive patients (median age 43 years) who underwent autologous blood stem cell transplantation (ABSCT) at a single institution to determine if CD34+ subsets (CD34+38-, CD34+33-, CD34+33+, CD34+41+) or various clinical factors affect hematopoietic engraftment independent of the total CD34+ cell dose/kg. Using Cox proportional hazards models, the factors independently associated with rapid neutrophil engraftment were higher CD34+ dose/kg, use of G-CSF post-ABSCT, and conditioning regimen (single-agent melphalan +/- TBI slower). Factors independently associated with rapid platelet engraftment were higher CD34+ cell dose/kg, higher ratio of CD34+33-/total CD34+ cells infused, conditioning regimen (mitoxantrone, vinblastine, cyclophosphamide faster), and no CD34+ cell selection of the autograft. The CD34+ cell selection process seemed to deplete CD34+41+ cells to a greater extent than total CD34+ cells which may explain our observation that it resulted in slower platelet engraftment. In conclusion, the total CD34+ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34+ subset. Platelet engraftment, however, was also influenced by the ratio of CD34+33-/total CD34+ cells for unmanipulated autografts, and possibly by the CD34+41+ dose for autografts manipulated by CD34+ selection. The use of CD34+ subsets requires further investigation in predicting engraftment of autografts which undergo ex vivo manipulation.

Adult↗
PubMed1999

Physical education for deaf students.

An ideal physical education program would be one that focuses on aspects leading to lifelong participation in and enjoyment of physical activity accompanied by appropriate fitness levels. Often, physical education classes are the only physical activity that many children receive throughout the day, and without them, an even greater number of children, including those who are deaf, would be prone to aspects associated with sedentary lifestyles. Schools need to involve their students in daily physical education classes. The emphasis of such a program should be placed on promoting physical fitness and developing skills that lead to a lifelong enjoyment of physical activity and healthy lifestyles. This paper reviews the literature on the state of physical fitness among deaf students and describes an exemplary physical education program that was implemented at a school for deaf children.

Adolescent↗
PubMed1999

An overview of nasal CPAP therapy in the management of obstructive sleep apnea.

Obstructive sleep apnea is readily reversible with nasally administered continuous positive airway pressure, although its effectiveness can be limited by poor patient compliance with therapy. With recent developments in technology, the ability to both diagnose and manage this disorder is dramatically improving. Assessment and therapeutic intervention can now be carried out not only in attended settings, such as sophisticated sleep laboratories, but in semiattended and unattended situations, including the home. What impact these advances will have on improving patient tolerance to therapy and reducing long-term clinical consequences of obstructive sleep apnea remains to be seen. However, there is no doubt that sleep-trained professionals now have many more tools at their disposal to diagnose and treat this disorder.

Humans↗
PubMed1998

Compliance of clinical stage I nonseminomatous germ cell tumor patients with surveillance.

PURPOSE: We evaluate compliance and its effect on the outcome of patients with clinical stage I nonseminomatous germ cell tumor who underwent post-orchiectomy surveillance at the Tom Baker Cancer Centre. MATERIALS AND METHODS: From 1980 to 1994, 76 evaluable patients underwent surveillance at the Tom Baker Cancer Centre. The surveillance protocol consisted of clinical evaluation, chest x-ray and serum tumor marker measurements monthly in year 1, every 2 months in year 2, every 6 months in years 3 to 5 and yearly in years 6 to 10. Abdomen and pelvic computerized tomography (CT) were scheduled every 2 months in year 1 and every 4 months in year 2. Noncompliance was defined as missing 2 or more consecutive clinic visits, tumor marker measurements or chest x-rays or 1 or more CT scans. RESULTS: Compliance with clinical evaluations was 61.5% in year 1 and 35.5% in year 2, whereas compliance with CT was only 25% and 11.8% in years 1 and 2, respectively. By univariate analysis diagnosis before 1990 predicted noncompliance, while age, marital status and distance from the center did not. Recurrent disease was detected in 28 patients (37%) at a median of 5.5 months after orchiectomy (range 1 to 49.5). Among the 47 compliant patients 23 had relapse and none died. Among the 29 noncompliant patients 5 had relapse and 2 died with central nervous system disease. CONCLUSIONS: Overall compliance with this surveillance program was poor but this study was too small to demonstrate whether poor compliance adversely affects overall survival.

Adolescent↗
PubMed1998

Benefit of aggressive multimodality therapy with autologous stem cell support for intra-abdominal desmoplastic small round cell tumor.

A case is described of a 19-year-old man with poor prognosis intra-abdominal desmoplastic small round cell tumor, who achieved a durable complete remission after aggressive multimodality treatment. He was diagnosed with a large peri-rectal mass and bulky metastases to the peritoneum, omentum and liver. He achieved a partial response to six courses of chemotherapy with VAC (vincristine, adriamycin, actinomycin, cyclophosphamide) and VIP (VP-16, ifosfamide, cisplatin). This was followed by resection of the omentum and cryotherapy to six of the liver lesions. He then achieved a complete response following high-dose busulfan 16 mg/kg and melphalan 140 mg/m2 with autologous stem cell support. Finally, pelvic radiotherapy was given to consolidate the remission. Twenty-six months following his diagnosis, and 19 months after the transplant, he remains well with no clinical or radiologic evidence of recurrent disease. This case report suggests a role for autologous stem cell transplantation as part of multimodality therapy for this unusual and aggressive malignancy.

Abdominal Neoplasms↗
PubMed1997

Primary prevention of eating disorders: might it do more harm than good?

OBJECTIVE: The aim of this pilot study was to evaluate a new school-based eating disorder prevention program designed to reduce dietary restraint. METHOD: Forty-six school-girls, aged 13-14 years, took part. The intervention consisted of eight weekly sessions of 45 min duration. A battery of self-report questionnaires was administered before and after the intervention and 6 months later. RESULTS: Unlike previous prevention studies, there was not only an increase in knowledge at postintervention but there was also a decrease in target behavior and attitudes. However, these effects were short-lived since they had disappeared 6 months later: indeed, at 6-month follow-up there was an increase in dietary restraint compared with baseline. DISCUSSION: These findings suggest that the intervention had been counterproductive since it led to an increase in dietary restraint. They imply that school-based prevention programs may do more harm than good.

Adolescent↗
PubMed1997

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: cost, safety, and long-term efficacy.

BACKGROUND: Few data are available on the cost, safety, and long-term efficacy of single-agent high-dose melphalan (HDM) followed by autologous bone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvage therapy of Hodgkin's disease (HD). PATIENTS AND METHODS: From February 1981 to September 1996, 23 patients with relapsed (n = 15) or refractory (n = 8) HD received salvage therapy with HDM 140-200 mg/m2 followed by non-cryopreserved ABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996, from initial consultation until transfer back to referring physician, was determined and compared to the estimate costs of two multi-agent regimens commonly used for HD. RESULTS: HDM was well tolerated with no early transplant-related mortality. The five-year overall and progression-free survival rates were 52% and 50%, respectively. The average total cost in Canadian funds of HDM/ABSCT in 1996 was $34,400/patient. This cost was estimated to be $4,700-6,800 cheaper per patient than the multi-agent high-dose regimens. CONCLUSION: These data suggest that HDM is safe, feasible, active, and reasonably inexpensive salvage therapy for patients with relapsed/refractory HD.

Adolescent↗