Search PubMed⌕ Search

Biomedical subjects

R M Wong

Publications and source records attributed to R M Wong.

35 records · Page 2Linked to original sources
PubMed1997

Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies.

PURPOSE: To determine the effect of age on the outcome of autologous bone marrow transplantation (ABMT) and/or peripheral-blood progenitor-cell (PBPC) transplantation. PATIENTS AND METHODS: A retrospective analysis was performed on 500 consecutive patients who ranged in age from 1 to 65 years (median, 40) with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), multiple myeloma (MM), or acute nonlymphoblastic leukemia (AML) who underwent autologous hematopoietic-cell transplant procedures at Stanford University Medical Center. RESULTS: The actuarial 5-year event-free survival (EFS) rate was 44%, the relapse rate 47%, and the regimen-related mortality (RRM) rate 8.6%. Disease status at time of transplantation, categorized as either minimal or advanced disease, was the strongest predictive factor for EFS (relative risk (RR) for advanced-disease group, 1.8; P < .0003) and relapse rate (RR for advanced-disease group, 1.9; P < .0004). Patients with minimal or advanced disease had an EFS rate of 48% and 30% and relapse rates of 43% and 72%, respectively. The EFS rate of patients less than 50 years verus > or = 50 years of age was 46% versus 34% (P = .03). Cox regression analysis showed that age was predictive for EFS (RR for patients 50 to 65 years, 1.4; P = .03). The actuarial RRM rate for these age groups was 7.4% versus 12.7% (P = .07), respectively. Multivariate analysis demonstrated that age (odds ratio [OR] for patients 50 to 65 years, 1.9; P < .05) and period of transplantation (OR for most recent years [1991 to 1995], 0.6; P = .06) were the most predictive factors for RRM. CONCLUSION: Although age greater than 50 years is associated with an inferior outcome following autologous hematopoietic-cell transplantation, it does not appear to be warranted to limit this potentially curative procedure based solely on age. The upper age limit of high-dose therapy with autologous progenitor-cell and/ or bone marrow support remains to be defined.

Adolescent↗
PubMed1997

Minimum inhibitory concentration of various single agents and the effect of their combinations against Helicobacter pylori, as estimated by a fast and simple in vitro assay method.

OBJECTIVES: Fast and simple in vitro methods of accurately assaying anti-Helicobacter pylori (H. pylori) activity are needed to facilitate the selection of optimal drugs for the eradication of H. pylori. With that purpose in mind, we developed a broth microdilution technique that uses a 96-well flat-bottom microplate. METHODS: Clinical isolates of H. pylori were placed in 25-cm2 tissue culture flasks and were grown in an atmosphere of 5% CO2 in air at 37 degrees C and 100% humidity. Then they were inoculated in 96-well flat-bottom microplates. After 24 h, the bacterial growth was assessed by automatic measurement at A450 with a microplate reader. Minimum inhibitory concentrations (MICs) of 11 drugs against H. pylori and the effect of two-drug combinations were respectively evaluated by the broth microdilution technique and by calculating the fractional inhibitory concentration index according to the checkerboard titration method. RESULTS: The MICs of all drugs tested with this system roughly agreed with those of previous reports in which the agar dilution method was used. The MIC of lansoprazole, a proton pump inhibitor, was low (0.88 microg/ml) and surpassed that of metronidazole (3.15 microg/ml). The effect of the combination of macrolide antibiotics with tetracycline was favorable. The proton pump inhibitor demonstrated a strong additive effect with macrolide antibiotics and fostered the activity of ecabet sodium (mucosal protective agent). CONCLUSION: This system could estimate the MIC of individual drugs quickly and simply, and could accurately measure the efficacy of two-drug combinations in vitro.

Anti-Bacterial Agents↗
PubMed1996

High dose etoposide-based myeloablative therapy followed by autologous blood progenitor cell rescue in the treatment of multiple myeloma.

BACKGROUND: A number of studies have demonstrated that high dose chemotherapy, with or without radiotherapy, with autologous marrow and/or peripheral blood progenitor cell support can result in improved overall and complete response rates in patients with multiple myeloma, and a minority of patients become long term survivors. Based on their favorable experience with high dose etoposide-based regimens in patients with Hodgkin's disease and non-Hodgkin's lymphoma, the authors explored the use of these regimens prior to autologous progenitor cell rescue in patients with multiple myeloma. METHODS: Thirty-four patients (median age, 49 years; range, 38-65) with multiple myeloma who were responsive to standard chemotherapy were enrolled in this study. Blood progenitor cells were collected after treatment with cyclophosphamide at a dose of 4 g/m2 followed by granulocyte-colony stimulating factor (G-CSF) at a dose of approximately 10 micrograms/kg/day subcutaneously, and the collection continued daily until the target number of mononuclear cells had been obtained. The preparative regimen consisted of fractionated total body irradiation (FTBI) of 1200 centigray in 10 fractions on Day -8 to Day -5, etoposide 60 mg/kg intravenously (i.v.) on Day -4, and cyclophosphamide 100 mg/kg i.v. on Day -2. Day 0 was the day of progenitor cell infusion. Patients who were older than 50 years or had received prior radiation therapy that precluded FTBI received carmustine 15 mg/kg i.v. or lomustine 15 mg/kg orally on Day -6 rather than FTBI. G-CSF (5 micrograms/kg/day) was begun the day after progenitor cell infusion and continued until engraftment. RESULTS: Recovery of granulocytes to 500/microL occurred at a median of 9 days (range, 7-13), and platelet recovery to 20,000/microL occurred without transfusion at 9 days (range, 6-88) after progenitor cell infusion. Thirty-two patients were evaluable for response. Eleven patients (34%) achieved a complete remission, 17 (53%) achieved a partial remission, and 4 (13%) had stable disease following high dose therapy and progenitor cell rescue. The actuarial event free survival at 4 years for the entire group was 26%, and overall survival was 36%. The median time to progression of disease was 13 months (range, 2-42). Two patients died of regimen-related toxicity, one of venoocclusive disease of the liver and the other of multiorgan failure. In a multivariate analysis, only the extent of prior therapy was a significant prognostic factor for event free survival, and no significant factors were identified for overall survival. CONCLUSIONS: High dose etoposide-based myeloablative regimens followed by autologous blood progenitor cell rescue are relatively well tolerated and effective for the treatment of multiple myeloma, and a minority of patients become long term disease free survivors.

Adult↗
PubMed1996

Influence of preparatory regimen and source of hematopoietic cells on outcome of autotransplantation for non-Hodgkin's lymphoma.

The use of high-dose chemotherapy with or without total-body irradiation (TBI) followed by autologous hematopoietic cell transplantation is associated with improved survival for relapsed or refractory non-Hodgkin's lymphoma (NHL). Previous reports comparing preparatory regimens with or without TBI followed by autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell transplantation (PBPCT) for these patients did not demonstrate any survival difference between the different modalities. No randomized studies comparing survival for patients with NHL transplanted with radiochemotherapy vs. chemotherapy alone have been reported. We treated 221 patients with high-risk, relapsed or refractory NHL with either chemotherapy alone or radiochemotherapy followed by ABMT or PBPCT. The patients were assigned preparatory regimens in a non-randomized manner and this analysis was performed to evaluate differences in outcome with the two preparatory regimens. Actuarial five-year event-free survival (EFS) was similar in patients receiving fractionated total-body irradiation (FTBI) plus etoposide (VP-16) and cyclophosphamide (Cy) compared with chemotherapy alone consisting of carmustine (BCNU) plus identical doses of VP-16 and Cy (52% vs. 46%, p = 0.08). Overall survival (OS) favored radiochemotherapy (61%) compared with chemotherapy alone (53%, p = 0.02). The relapse rate was the same in both groups (41%), whereas the transplantation-related mortality (TRM) was similar in patients receiving chemotherapy alone and those receiving radiochemotherapy (13% vs. 7% respectively, p = 0.30). Proportional hazards analysis of significant variables including preparatory regimen found only the number of prior relapses to be predictive of EFS. Fewer number of prior relapses, radiochemotherapy and PBPCT were significant predictors of favorable OS. In additional analyses, the improved OS of the radiochemotherapy regimen was confirmed only for patients receiving ABMT but was not a significant predictor of outcome in patients transplanted with PBPCT. From these retrospective data we conclude: 1) PBPCT resulted in survival superior to that of ABMT; 2) the risk of relapse is similar with either preparatory regimen; 3) patients with fewer prior relapses enjoyed superior overall and event-free survival as well as fewer relapses; and 4) there were no significant differences in the two preparatory regimens when combined with PBPCT in relapsed or refractory NHL.

Adolescent↗
PubMed1996

Paradoxical effect of thalidomide prophylaxis on chronic graft-vs.-host disease.

Thalidomide has been reported to be an effective agent for the treatment of chronic graft-vs.-host disease (GVHD). To determine its efficacy as a prophylactic agent for the prevention of chronic GVHD, a prospective randomized double-blind study was performed. A total of 59 patients were randomized to receive either placebo or thalidomide (200 mg orally twice a day) beginning 80 days after allogeneic bone marrow transplantation (BMT). Fifty-four evaluable patients were analyzed, 26 received placebo, and 28 received thalidomide. The characteristics of patients were well-balanced between the two groups. Following the first interim analysis conducted by the Data Safety Monitoring Board using an intent-to-treat approach, a statistically significant difference in the incidence of chronic GVHD was found. Patients receiving thalidomide developed chronic GVHD more often than patients receiving placebo (p = 0.06). Moreover, an apparent overall survival advantage was noted for patients receiving placebo compared to those receiving thalidomide (p = 0.006). Adjustment for possible confounding factors did not eliminate these negative effects of thalidomide. These results demonstrate that while thalidomide is an effective agent for the therapy of chronic GVHD, its use at the doses administered for the prophylaxis of chronic GVHD resulted in a paradoxical outcome with a higher incidence of chronic GVHD and a lower overall survival. We conclude that the early use of thalidomide results in a shift in the balance between GVHD and induction of tolerance. These data demonstrate again the importance of phase III double-blind controlled randomized studies.

Adolescent↗
PubMed1995

A new preparatory regimen for autologous bone marrow transplantation for patients with lymphoma.

BACKGROUND: This trial studied the feasibility and efficacy of a new preparatory regimen for autologous bone marrow transplantation for patients with advanced lymphoid malignancies. METHODS: Twenty-one patients with Hodgkin's disease (n = 12) and non-Hodgkin's lymphoma (n = 9) were treated in this study. Lomustine was substituted for carmustine) in a dose-escalation study with an initial dose of 6 mg/kg and increasing by 3 mg/kg in groups of four patients. The preparatory regimen consisted of lomustine (6-15 mg/kg) orally on Day -6, etoposide (60 mg/kg) intravenously (i.v.) on Day -4, and cyclophosphamide (100 mg/kg) i.v. on Day -2. Peripheral blood progenitor cells and/or bone marrow were infused on Day 0. RESULTS: Lomustine was well tolerated in all patients with no significant toxicity specific to this drug. Engraftment was prompt: the time to achieving greater than or equal to 500 granulocytes/microliters was 12 days (range, 9-16 days) and the time to achieving greater than or equal to 25,000 platelets/microliters without transfusion support was 16 days (range, 9-22 days). Five patients experienced interstitial pneumonitis, three of whom had active or recent interstitial pneumonitis before bone marrow transplantation, and one who just completed mantle irradiation. Three patients died from this preparatory regimen, one of progressive interstitial pneumonitis, one of Legionella pneumonia, and one of multiorgan failure. Three patients with non-Hodgkin's lymphoma relapsed. Fourteen patients are currently alive and disease free to date. The actuarial are currently alive and disease free to date. The actuarial disease free survival was 57%, with a median follow-up of 23 months (range, 1-48 months). CONCLUSION: The preparatory regimen consisting of lomustine/etoposide/cyclophosphamide is active in treating patients with lymphomas. Further trials with high doses of lomustine are warranted.

Adolescent↗
PubMed1994

High-resolution restriction map for a 240-kilobase region spanning 91 to 96 minutes on the Salmonella typhimurium LT2 chromosome.

A hierarchical approach allows the completion of contiguous sets of overlapping clones for small regions of a genome, one at a time rather than tackling the whole genome at once. On the basis of the BlnI restriction map for Salmonella typhimurium LT2, we dissected the chromosome into 21 different fragments by using a Tn5 transposon carrying a BlnI site. Dissected chromosomal fragments were purified by pulsed-field gel electrophoresis and used as probes for sorting a lambda DASHII genomic library of 2,304 primary clones. A total of 129 clones identified as spanning the region from 91 min to 98 min were partly ordered on the basis of the intensity of hybridization with mitomycin-induced Mud-P22 phage DNAs from insertions with pac sites in opposite orientations at 93 min used as probes. Decreased signal intensity with the Mud-P22 probes corresponded to the increased distance of the clone from the site of Mud-P22 insertion and allowed the clones to be placed in two groups from 91 min to 93 min and from 93 min to 98 min and into four intensity categories within the two groups. A member of each category was used to generate a riboprobe from the T3 promoter flanking the insert. This probe identified overlapping clones among the 129 clones. This subchromosomal library was then screened again with riboprobes from nonoverlapping clones. After four cycles of this strategy, a minimal contiguous sequence of 19 partly overlapping clones was selected for restriction mapping. A detailed map of 378 sites for eight restriction enzymes is presented for a region of about 240 kb. Working clockwise, the following genes were placed on this physical map on the basis of their restriction maps: malFEK, lamB, malM, lexA, qor, dnaB, alr, uvrA, proP, pmrB, pmrA, melA, melB, phoN, amiB, mutL, and miaA.

Bacteriophage lambda↗
PubMed1993

Busulfan/etoposide--initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia.

Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4-HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4-HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of > or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count > or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit > or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

Adult↗
PubMed1992

Dynamic assessment of quality of life after autologous bone marrow transplantation.

To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.

Adult↗
PubMed1976

A controlled trial of intravenous salbutamol and aminophylline in acute asthma.

In a randomized double-blind trial an intravenous injection of salbutamol (100mug) was compared with an intravenous injection of aminophylline (250mg) in 23 patients with acute exacerbations of asthma. Salbutamol (11 cases) and aminophylline (12) produced a mean proportionate increase in FEV of 26% and 23% respectively. Blood gas pressures showed a trend to improvement with a mean rise in oxygen tension of 2mm Hg(0-2kPa) in the aminophylline group and of 6mm Hg (0-8kPa) in the salbutamol group. Electrocardiogram patterns also showed overall improvement, and mean decreases in pulse rate of 8 beats per minute and 2 beats per minute were noted in the aminophylline and salbutamol groups respectively. Differences in results did not reach conventional levels of significance and no serious side effects were noted. It was concluded that in the doses and routes of administration compared, salbutamol was as effective as aminophylline.

Acute Disease↗
PubMedDate not supplied

Effect of oral glutamine supplementation during bone marrow transplantation.

BACKGROUND: Because all patients receiving bone marrow transplant (BMT) and peripheral blood progenitor cell transplant (PBPCT) experience gastrointestinal (GI) toxicity from the preparative regimen of chemotherapy, with or without radiation, oral glutamine was administered during the preparatory regimen and after transplant to maintain GI structure and function. METHODS: To evaluate effects of oral glutamine on nutritional status and overall outcome, a prospective, randomized, double-blinded study was performed on 58 autologous and allogeneic BMT patients. Patients received 30 g of oral glutamine or placebo daily. RESULTS: The trends of decreased median length of stay and the median number of days of total parenteral nutrition (TPN) were seen in the group supplemented with the >0.285-g/kg (the recommended dosage) dose of glutamine; however, there was no statistically significant difference in the nutritional status and overall patient outcome as assessed by days receiving TPN, number of days required until oral intake resumed, length of hospitalization, number of days and highest grade of mucositis, and quantity and number of days of diarrhea. CONCLUSIONS: This study does not support the hypothesis that oral glutamine may offer benefit. Further investigation is required regarding clinical tools for determining effectiveness, administration for tolerance and compliance, dosage, and potential of oral glutamine usage.

Administration, Oral↗
PubMedDate not supplied

[Genetic influence on energy requirements. I. Development of an experimental model].

In attempting to explore the mechanisms of interaction of genetic and environmental factors that affect the quantitative requirements of energy by man, the convenience of an animal model was considered and searched for. The idea was to start with male and female Wistar rats and through inbreeding segregate the highly effective users of energy from the poor users. The efficiency of dietary energy utilization was measured by the index of conversion (IC) defined as the dietary intake necessary to increase 1 g of body weight in a 32-day period, from day 21st to day 52nd of extrauterine life. The median value of the IC for all animals included in each experiment was the cut-off point to classify each individual as a good or a poor energy user. The first generation had three males and five females with a median IC = 2.90 and a range from 2.54 to 3.25. The proportion of males below the median was 3/3 while the proportion of females was 2/5. The difference in proportions was striking and led immediately to the consideration of a sex-link hypothesis, and to test it the, IC of 91 Wistar rats randomly selected at birth was obtained. The median value of the series was 2.99 with a range from 2.24 to 3.95. The proportion of male rats with values below the median was 33/38 while the corresponding proportion for females rats was 13/53. In other words, while nine of every ten male animals were good users of energy, only two out of ten females fell into this category.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Neurological manifestations in Japanese Ama divers.

Repetitive breath-hold (BH) diving can lead to accumulation of nitrogen (N2) in blood and tissues, which may give rise to decompression illness (DCI). An unusual condition is "Taravana", the diving syndrome reported by Cross in the 1960s. That report generated wide discussion as to whether BH diving can cause DCI. Paulev was the first person to suggest the link between DCI and BH diving. He, a submarine medical officer developed symptoms of DCI after a series of BH dives, having proceeded the dives by spending time in a hyperbaric chamber at 20 meters for 8 minutes. Recently four professional Japanese BH divers (Ama) with histories of diving accidents were reported. Magnetic resonance imaging of these divers detected cerebral infarcts localized in the watershed areas of the brain. A survey conducted on their island revealed that many Ama divers had experienced stroke-like events. A clinical feature of DCI in BH diving is that the damage is limited to the brain. Although the mechanisms of brain damage in BH diving are unclear, N2 bubbles passing through the lungs or the heart so as to become arterialized are most likely to be the etiological factor.

Adult↗