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D Louie

Publications and source records attributed to D Louie.

At least 19 recordsLinked to original sources
PubMed2004

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

BACKGROUND: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. PATIENTS AND METHODS: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible. RESULTS: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age. CONCLUSIONS: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.

Adolescent↗
PubMed2001

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model.

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Adolescent↗
PubMed1999

Single-event analysis of the packaging of bacteriophage T7 DNA concatemers in vitro.

Bacteriophage T7 packages its double-stranded DNA genome in a preformed protein capsid (procapsid). The DNA substrate for packaging is a head-to-tail multimer (concatemer) of the mature 40-kilobase pair genome. Mature genomes are cleaved from the concatemer during packaging. In the present study, fluorescence microscopy is used to observe T7 concatemeric DNA packaging at the level of a single (microscopic) event. Metabolism-dependent cleavage to form several fragments is observed when T7 concatemers are incubated in an extract of T7-infected Escherichia coli (in vitro). The following observations indicate that the fragment-producing metabolic event is DNA packaging: 1) most fragments have the hydrodynamic radius (R(H)) of bacteriophage particles (+/-3%) when R(H) is determined by analysis of Brownian motion; 2) the fragments also have the fluorescence intensity (I) of bacteriophage particles (+/-6%); 3) as a fragment forms, a progressive decrease occurs in both R(H) and I. The decrease in I follows a pattern expected for intracapsid steric restriction of 4',6-diamidino-2-phenylindole (DAPI) binding to packaged DNA. The observed in vitro packaging of a concatemer's genomes always occurs in a synchronized cluster. Therefore, the following hypothesis is proposed: the observed packaging of concatemer-associated T7 genomes is cooperative.

Bacteriophage T7↗
PubMed1999

Mitochondrial DNA variation in bull trout (Salvelinus confluentus) from northwestern North America: implications for zoogeography and conservation.

Bull trout, Salvelinus confluentus (Salmonidae), are distributed in northwestern North America from Nevada to Yukon Territory, largely in interior drainages. The species is of conservation concern owing to declines in abundance, particularly in southern portions of its range. To investigate phylogenetic structure within bull trout that might form the basis for the delineation of major conservation units, we conducted a mitochondrial DNA (mtDNA) survey in bull trout from throughout its range. Restriction fragment length polymorphism (RFLP) analysis of four segments of the mtDNA genome with 11 restriction enzymes resolved 21 composite haplotypes that differed by an average of 0.5% in sequence. One group of haplotypes predominated in 'coastal' areas (west of the coastal mountain ranges) while another predominated in 'interior' regions (east of the coastal mountains). The two putative lineages differed by 0.8% in sequence and were also resolved by sequencing a portion of the ND1 gene in a representative of each RFLP haplotype. Significant variation existed within individual sample sites (12% of total variation) and among sites within major geographical regions (33%), but most variation (55%) was associated with differences between coastal and interior regions. We concluded that: (i) bull trout are subdivided into coastal and interior lineages; (ii) this subdivision reflects recent historical isolation in two refugia south of the Cordilleran ice sheet during the Pleistocene: the Chehalis and Columbia refugia; and (iii) most of the molecular variation resides at the interpopulation and inter-region levels. Conservation efforts, therefore, should focus on maintaining as many populations as possible across as many geographical regions as possible within both coastal and interior lineages.

Animals↗
PubMed1999

Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma.

PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granulocyte colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34(+) cells collected after treatment with ICE and G-CSF were evaluated. RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P =.003). The median number of CD34(+) cells/kg collected was 8.4 x 10(6). The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects. CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.

Adolescent↗
PubMed1997

Familial Hodgkin's and non-Hodgkin's lymphoma: different patterns in first-degree relatives.

In order to evaluate the importance of genetic susceptibility in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) we retrospectively analysed 31 families with lymphoma in first-degree relatives containing a total of 65 affected persons. We observed 20 HD/HD, 8 NHL/HD and 8 NHL/NHL pairs with median ages of diagnosis of 27, 36 and 48 years, respectively (p < 0.001). In HD/HD sib pairs were predominant in contrast to parent/child pairs in NHL/NHL (p = 0.04). There was a higher frequency of diseases with impaired immune function in NHL/NHL than in other pairs (p = 0.01). Comparison of ages and times of incidence of the pairs as well as sex-concordance rates are consistent with an age-specific genetic susceptibility to HD, but suggest a time-specific exposure in some NHL-prone families with or without compromised immune function.

Adolescent↗
PubMed1996

Processing of pro-opiomelanocortin in GH3 cells: inhibition by prohormone convertase 2 (PC2) antisense mRNA.

The processing of pro-opiomelanocortin (POMC) was examined in GH3 cells, a rat sommatomammotrope cell line, by transiently-transfecting the cells with mouse POMC cDNA. The peptide products were extracted, chromatographed on HPLC and identified by specific radioimmunoassay. POMC was processed to generate ACTH-related peptides, beta-endorphin and Lys-gamma 3- MSH, with complete disappearance of the POMC precursor. The ACTH-related molecules were identified as ACTH1-14, ACTH1-15, ACTH1-17, as well as ACTH1-39. GH3 cells which were not transfected with POMC cDNA did not contain endogenous POMC-related peptides. RT-PCR demonstrated that GH3 cells contain prohormone convertase 2 (PC2) mRNA but no PC1 mRNA. To determine if PC2 was the enzyme responsible for POMC processing in this cell line, GH3 cells were stably-transfected with PC2 antisense cDNA. A cell line was obtained which showed an absence of PC2 protein compared to control untransfected GH3 cells, indicating successful hybridization of PC2 antisense mRNA to the endogenous PC2 mRNA. When this cell line was then transiently-transfected with POMC cDNA, POMC was not processed. The results from these experiments suggest that PC2 alone can correctly process POMC to biologically active smaller peptides in vivo. Additionally, the GH3 cell line with and without incorporation of PC2 antisense cDNA can be used as a model system to study the role of PC2 in the post-translational processing of other prohormones and proproteins in vivo.

Animals↗
PubMed1995

A randomized trial of self-help materials, personalized feedback, and telephone counseling with nonvolunteer smokers.

The incremental effects of (a) a self-help booklet alone, (b) self-help booklet with computer-generated personalized feedback, and (c) self-help booklet, personalized feedback, and outreach telephone counseling were evaluated in a population-based, nonvolunteer sample of smokers. Smokers (N = 1,137) were identified through a telephone survey of a random sample of 5,903 enrollees in a health maintenance organization and randomized to a no-treatment control group or 1 of the 3 intervention conditions. Smoking status was ascertained 3, 12, and 21 months postrandomization. Cotinine validation of self-reported cessation was obtained at the 12-month follow-up. Overall, the telephone counseling significantly increased smoking cessation at the 3-month follow-up, but not at 12 or 21 months. Among smokers who were precontemplative at baseline, telephone counseling significantly increased prevalent abstinence at 3 and 12 months and continuous abstinence at 21 months (defined as self-reported abstinence at 3, 12, and 21 months).

Adult↗
PubMed1995

A desktop, low-cost video fluorometer for quantitation of macromolecules after gel electrophoresis.

After gel electrophoresis, quantification of in-gel fluorescence is sometimes used to assay the macromolecules fractionated. Both procedures and equipment that have the following improvements are presented here for direct video fluorometry of gels used for electrophoresis: comparatively low cost, high ease of use and low consumption of space. This equipment has a linear response to the amount of ethidium-stained DNA that forms a band in an agarose gel.

DNA, Viral↗
PubMed1995

Nasopharyngeal carcinoma. A study examining Asian patients treated in the United States.

From 1972 to 1991, 126 Asian patients with nasopharyngeal carcinoma underwent definitive radiation therapy for locoregional disease: 86 men, 40 women. Median age was 50. All patients received external-beam irradiation with cobalt 60 or 4-18 MV x-rays. Local recurrence, regional recurrence, and distant metastases were 22%, 11%, and 23%, respectively. Local recurrence progressively increased with increasing T stage, but doses in those who recurred did not differ from the group as a whole. Regional recurrence was not associated with T or N stage or dose. Patients with N2 disease had the highest distant metastatic rate. The 5- and 10-year overall survival rates were 54% and 38%, respectively. Of age, gender, and histology, only age less than 50 was found to be favorably prognostic. No severe long-term complications were observed, and acute reactions were acceptable. Our survival results are comparable with results found both in Asia and North America. Nonetheless, altered fractionation techniques and/or other radiation modalities should be further explored to improve locoregional control.

Adult↗
PubMed1994

Quantification of the effect of excluded volume on double-stranded DNA.

By steric exclusion of volume, neutral polymers both condense and increase the effective concentration of DNA random coils. Neutral polymers also stimulate the in vitro packaging of DNA in the capsids of some double-stranded DNA bacteriophages. In the present study, the physical effects of neutral polymers on DNA random coils have been quantified by assaying the DNA products at equilibrium of the following two reactions of the 12 nucleotide single-stranded complementary (cohesive) ends of mature bacteriophage lambda DNA: bimolecular joining of half-molecules of mature lambda DNA, and cyclization of intact lambda DNA; cyclization is used as a probe for unimolecular DNA condensation. The smaller neutral molecules, including polyethylene glycol of molecular mass 200 Da (PEG200), shift both reactions towards dissociation; this shift is partially correlated with reduced water activity. The larger PEGs (molecular mass of 1540 or more) shift both reactions towards association. Water activity-corrected equilibrium constants for the larger PEGs are found to increase as a function of PEG concentration. Below 2% to 3% (w/v) PEG, these equilibrium constants are independent of PEG molecular mass; at higher PEG concentrations, these equilibrium constants increase as the molecular mass of the PEG increases. The following conclusions are drawn. (1) Volume exclusion among PEG molecules is the primary cause of the PEG molecular mass-dependence of excluded volume. (2) At the lower PEG concentrations, the PEG radius obtained by quantification of excluded volume is usually equal to the hydrodynamic PEG radius. (3) At any given PEG concentration, the PEG-DNA excluded volume is approximately the same for bimolecular DNA joining as it is for unimolecular DNA cyclization. (4) Polymer-induced stimulation of in vitro bacteriophage DNA packaging is derived primarily from alteration of water activity, not alteration of excluded volume.

Bacteriophage T7↗
PubMed1994

Medical conditions and motor vehicle collision injuries in older adults.

OBJECTIVE: To determine whether medical conditions that can impair sensory, cognitive, or motor function increase the risk of injury due to motor vehicle collision in older drivers. DESIGN: Case-control study. SETTING: Group Health Cooperative of Puget Sound, a large prepaid health plan. PARTICIPANTS: Group Health members age 65 or older who were licensed drivers in 5 counties. Cases were injured while driving during 1987 or 1988. Controls were matched to cases on age, gender, and county of residence but experienced no such injury during the study years. MEASUREMENTS: The outcome was injury requiring medical care due to a police-investigated motor vehicle collision. Risk factors evaluated included selected medical conditions active within the previous 3 years, as determined from the medical record. MAIN RESULTS: Injury risk was 2.6-fold higher in older diabetic drivers (95% CI: 1.4-4.7), especially those treated with insulin (odds ratio [OR] = 5.8, 95% CI: 1.2-28.7) or oral hypoglycemic agents (OR = 3.1, 95% CI: 0.9-11.0), those with diabetes for over 5 years (OR = 3.9, 95% CI: 1.7-8.7), and those with both diabetes and coronary heart disease (OR = 8.0, 95% CI: 1.7-37.7). Increases were also found for older drivers with coronary artery disease (OR = 1.4), depression (OR = 1.7), alcohol abuse (OR = 2.1), or falls (OR = 1.4), but these associations could easily have arisen by chance. CONCLUSIONS: Counseling about driving risks may be warranted for certain elderly diabetic drivers. Further research is needed to determine whether transient hypoglycemia or long-term complications explain these effects.

Accidents, Traffic↗
PubMed1994

Implementation and acceptance of outreach telephone counseling for smoking cessation with nonvolunteer smokers.

Brief supportive telephone counseling is a promising adjunct to self-help smoking cessation programs. This article reports rates of participation, predictors of participation, and content of telephone counseling calls with nonvolunteer smokers who were identified through health surveys administered to a random sample of enrollees in a health maintenance organization. Eighty-six percent of smokers accepted at least one of three counselor calls; 66% accepted all three calls. Baseline characteristics associated with acceptance of calls included being female and greater average length of time to the first cigarette of the day. Acceptance did not differ significantly by stage of cessation. First calls with smokers who accepted all three calls were longer and were more likely to be with smokers who were willing to take a specific next action step. Overall, 12% of the sample reported having quit smoking by the third counseling call, with the highest quit rate (23%) among smokers who, at baseline, were planning to quit in the next month. Implications for large-scale interventions with smokers in health care and other organizations are discussed.

Adult↗
PubMed1993

6q deletions define distinct clinico-pathologic subsets of non-Hodgkin's lymphoma.

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate-grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.

Biopsy↗
PubMed1993

Pulsed field agarose gel electrophoresis in the study of morphogenesis: packaging of double-stranded DNA in the capsids of bacteriophages.

To understand how comparatively simple macromolecular components become biological systems, studies are made of the morphogenesis of bacteriophages. Pulsed field agarose gel electrophoresis (PFGE) has contributed to these studies by: (i) improving the length resolution of both mature, linear, double-stranded bacteriophage DNAs and the concatemers formed both in vivo and in vitro by the end-to-end joining of these mature bacteriophage DNAs, (ii) improving the resolution of circular conformers of bacteriophage DNAs, (iii) improving the resolution of linear single-stranded bacteriophage DNAs, (iv) providing a comparatively simple technique for analyzing protein-DNA complexes, and (v) providing a solid-phase quantitative assay for all forms of bacteriophage DNA; solid-phase assays are both less complex and more efficient than liquid-phase assays such as rate zonal centrifugation. Conversely, studies of bacteriophages have contributed to PFGE the DNA standards used for determining the length of nonbacteriophage DNAs. Among the solid-phase assays based on PFGE is an assay for excluded volume effects.

Bacteriophages↗
PubMed1993

Fluorescence staining of nuclear deoxyribonucleic acid allows for accurate assessment of the hamster egg penetration assay.

To improve the assessment of sperm penetration during the hamster penetration assay, we compared the Hoechst 33342 and 33258 DNA-specific fluorescent stains with the standard acetolacmoid stain. The fluorescence stains produced distinct staining of the DNA within the egg cytoplasm and nucleus, and this allowed for accurate and fast assessment of sperm penetration.

Animals↗
PubMed1993

Zona opening with 308 nm XeCl excimer laser improves fertilization by spermatozoa from long-term vasectomized mice.

Spermatozoa from long-term vasectomized mice have greatly reduced fertilizing ability in vivo and in vitro, which makes this a useful animal model for male factor infertility. The purpose of this study was to evaluate the 308 nm XeCl excimer laser for opening the zona pellucida to enhance the fertilization rate with spermatozoa from vasectomized males. Inseminating zona-intact (control) oocytes with 5 x 10(6) spermatozoa/ml resulted in only 6% fertilization and 33.3% development to the blastocyst stage; zona-opened oocytes showed significant improvement with 31.5% fertilization, 90% cleavage to the 2-cell stage, and 72.2% blastocyst formation. Out of the 130 oocytes in the experimental group, zona ablation was performed successfully on 127 and only three were damaged. These results suggest that laser micromanipulation for assisted fertilization potentially offers a simplified and precise method for mechanical zona cutting.

Animals↗