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At least 541 records · Page 30Linked to original sources
PubMed1999

Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered.

PURPOSE: To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either > or = three cycles of high-dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. RESULTS: A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or > or = three cycles (n = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P =.03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received > or = three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. Furthermore, overall survival was also significantly compromised (P =.04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received > or = three cycles of high-dose cytarabine. CONCLUSION: These data demonstrate that failure-free survival and overall survival of patients with t(8;21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.

Adolescent↗
PubMed2001

Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial.

PURPOSE: Although high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse. PATIENTS AND METHODS: A randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs. RESULTS: After CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs (median, 3.1), with 54% of CD34-enriched products having no detectable tumor. Median time to count recovery, number of transfusions, transplantation-related mortality, and days in hospital were equivalent between the two transplantation arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and 34 patients (35%) in the unselected arm had died (P =.784). Median overall survival in the selected arm was reached at 50 months and is not reached at this time in the unselected arm (P =.78). Median disease-free survival was 100 versus 104 weeks (P =.82), with 67% of patients in the selected arm and 66% of patients in the unselected arm relapsing. CONCLUSION: This phase III trial demonstrates that although CD34 selection significantly reduces myeloma cell contamination in PBPC collections, no improvement in disease-free or overall survival was achieved.

Adult↗
PubMed2003

Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin's lymphoma.

PURPOSE: This study was undertaken to test the hypothesis that serum selenium concentration at presentation correlates with dose delivery, first treatment response, and overall survival in patients with aggressive B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: The patients presented between July 1986 and March 1999 and received anthracycline-based chemotherapy, radiotherapy, or both. The total selenium content was retrospectively analyzed in 100 sera, frozen at presentation, using inductively coupled plasma mass spectrometry. RESULTS: The serum selenium concentration ranged from 0.33 to 1.51 micromol/L (mean, 0.92 micromol/L; United Kingdom adult reference range, 1.07 to 1.88 micromol/L). Serum selenium concentration correlated closely with performance status but with no other clinical variable. Multivariate analysis revealed that increased dose delivery, summarized by an area under the curve, correlated positively with younger age (P <.001), advanced stage (P =.001), and higher serum selenium concentration (P =.032). Selenium level also correlated positively with response (odds ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.90; P =.011) and achievement of long-term remission after first treatment (log-rank test, 4.38; P =.036). On multivariate analysis, selenium concentration was positively predictive of overall survival (hazard ratio [HR], 0.76 for 0.2 micromol/L increase; 95% CI, 0.60 to 0.95; P =.018), whereas age indicated negative borderline significance (HR, 1.09; 95% CI, 0.99 to 1.18; P =.066). CONCLUSION: Serum selenium concentration at presentation is a prognostic factor, predicting positively for dose delivery, treatment response, and long-term survival in aggressive non-Hodgkin's lymphoma. Unlike most existing prognostic factors in aggressive non-Hodgkin's lymphoma, selenium supplementation may offer a novel therapeutic strategy in this frequently curable malignancy.

Adult↗
PubMed2003

Correlation of early metastatic response by 123I-metaiodobenzylguanidine scintigraphy with overall response and event-free survival in stage IV neuroblastoma.

PURPOSE: Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. PATIENTS AND METHODS: Seventy-five children older than 1 year and with stage IV neuroblastoma had 123I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance > 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. RESULTS: The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was < or = 0.5, or, if after four cycles, the relative score was < or = 0.24. Patients with a relative score of < or = 0.5 after two cycles or a score of < or = 0.24 after four cycles had an improved EFS rate (P =.053 and.045, respectively). CONCLUSION: Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.

3-Iodobenzylguanidine↗
PubMed2006

Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma.

PURPOSE: To evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types. PATIENTS AND METHODS: Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up. RESULTS: After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio [HR], 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001). CONCLUSION: Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.

Adipokines↗
PubMed2006

Dietary fat, fiber, vegetable, and micronutrients are associated with overall survival in postmenopausal women diagnosed with breast cancer.

Relatively few studies have assessed the relationship between dietary intakes and survival after breast cancer diagnosis. We investigated the influence of diet, including dietary fat (percentage energy), fiber, vegetable, and fruit intakes, and micronutrients (folate, carotenoids, and vitamin C) on overall survival in women diagnosed with breast cancer. Subjects were postmenopausal women diagnosed with breast cancer (N = 516) between 1994 and 1995 with a mean survival time of 80 mo (SD: 18). Subjects completed a food frequency questionnaire for the year prior to diagnosis. Cox proportional hazards models were used to measure the relationship between dietary intakes and death due to any cause after breast cancer diagnosis. In the multivariate analysis, we found that the hazard ratio [HR and 95% confidence interval (CI)] of dying in the highest tertile compared to the lowest tertile of total fat, fiber, vegetable, and fruit was 3.12 (95% CI = 1.79-5.44), 0.48 (95% CI = 0.27-0.86), 0.57 (95% CI = 0.35-0.94), and 0.63 (95% CI = 0.38-1.05), respectively (P <or= 0.05 for trend, except for fruit intake). Other nutrients including folate, vitamin C, and carotenoid intakes were also significantly associated with reduced mortality (P <or= 0.05 for trend). These results suggest that in postmenopausal women diagnosed with breast cancer, reduced dietary fat and increased fiber, vegetable, fruit, and other nutrient intakes associated with a plant-based, high-fiber diet improves overall survival after breast cancer diagnosis.

Body Mass Index↗
PubMed2006

Glucose activates a protein phosphatase-1-mediated signaling pathway to enhance overall translation in pancreatic beta-cells.

Both the rate of overall translation and the specific acceleration of proinsulin synthesis are known to be glucose-regulated processes in the beta-cell. In this study, we propose that glucose-induced stimulation of overall translation in beta-cells depends on a protein phosphatase-1-mediated decrease in serine-51 phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), a pivotal translation initiation factor. The decrease was rapid and detectable within 15 min and proportional to the range of glucose concentrations that also stimulate translation. Lowered net eIF2alpha phosphorylation was not associated with a detectable decrease in activity of any eIF2alpha kinase. Moreover, okadaic acid blocked glucose-induced eIF2alpha dephosphorylation, suggesting that the net effect was mediated by a protein phosphatase. Experiments with salubrinal on intact cells and nuclear inhibitor of protein phosphatase-1 (PP1) on cell extracts suggested that this phosphatase was PP1. The net effect contained, however, a component of glucose-induced folding load in the endoplasmic reticulum because coincubation with cycloheximide further amplified the effect of glucose on eIF2alpha dephosphorylation. Thus, the steady-state level of eIF2alpha phosphorylation in beta-cells is the result of a balance between folding-load-induced phosphorylation and PP1-dependent dephosphorylation. Because defects in the pancreatic endoplasmic reticulum kinase-eIF2alpha signaling system lead to beta-cell failure and diabetes, deregulation of the PP1 system could likewise lead to cellular dysfunction and disease.

Animals↗
PubMed1981

Overall management of ruptured aneurysm: comparison of early and late operation.

The overall management results with 61 consecutive patients admitted within 3 days of subarachnoid hemorrhage from a ruptured intracranial aneurysm were analyzed. During the course of this study, the preferred method of management shifted from late surgery (planned at least 7 days after the last hemorrhage) to early surgery (within 4 days of the last hemorrhage). Ten moribund patients were excluded from analysis, leaving 24 in the late group and 27 in the early group. Both groups had comparable patient demographic characteristics and neurological conditions, and their care was supervised by one neurosurgeon (N.F.K.). A microsurgical intracranial operation was performed on all patients who survived long enough to have surgery. The intraoperative conditions and complications were similar for the two groups. The average length of follow-up was 11 months in the late and 9 months in the early group. The overall management results for the late group showed a 42% favorable outcome, a 17% unfavorable outcome, and a 42% mortality. The early group had an 81% favorable outcome, a 7% unfavorable outcome, and an 11% mortality. Patients in both good and poor conditions fared better in the early group. Seven late group patients rebled, compared to none in the early group. The number of medical complications, the length of hospitalization, and the occurrence of symptomatic vasospasm were all greater in the late group. Vasospasm in the early group occurred only postoperatively and, with the aneurysms secured, was treated more aggressively and successfully with hypertensive/hypervolemic therapy than the predominantly operative vasospasm in the late group.

Adult↗
PubMed1996

The reduction of tumour control with increasing overall time: mathematical considerations.

The rate of loss of tumour control (dP/dt) with extension of treatment time is analysed to assess the relative contributions of radiobiological parameters (radiosensitivity, clonogen doubling time, clonogen numbers and fractionation schedule) on such loss. Linear quadratic modelling and Poisson statistics are used to study individual tumour responses. A heterogeneous tumour population is constructed by the use of random sampling techniques to allow for variations in intrinsic radiosensitivity and clonogen doubling times. Average tumour control probability is calculated for this population for two different fractionation schedules (60 Gy in 30 fractions and 50 Gy in 15 fractions), each given over 15-60 days. The magnitude of dP/dt will depend upon the tumour cure probability (P): the loss of control will be most significant for tumours which have a cure of 37% when the Poisson survival model is used. The analysis suggests that compensation for short unscheduled treatment gaps (e.g. by increasing the total dose or rescheduling with use of weekend treatment sessions) may only be required for difficult tumours (i.e. radioresistant and/or with short clonogen doubling times). Where pre-treatment clonogen numbers are relatively low as in small volume tumours or after surgical debulking, the model predicts that correction for short treatment gaps is probably not required if the average effective clonogen doubling times are longer than 5 days. Different dose-time-fractionation schedules, even though producing similar overall cure rates in clinical practice, may actually be achieving cures in different subpopulations within a population of tumours, since the value of dP/dt in each individual tumour will depend upon the set of radiobiological parameters given above. For a hypothetical randomly selected heterogeneous tumour population the predicted rates of loss of tumour control produced by an extension in treatment time are 0.9 and 1.1% per day, respectively, for the above fractionation schedules. These values are close to those reported in the clinical literature for the first 2 weeks of treatment prolongation (1-2% per day for squamous cell carcinomas). The Poisson method, when combined with random sampling techniques, consequently provides realistic data. Modelling of this clinical problem provides an insight into how tumour sub-populations, each characterized by its own set of radiobiological parameters, can influence the overall rate of loss of tumour control in a heterogeneous population. Random sampling techniques should be considered as necessary precursors for the assessment of the choices of dose-fractionation in future clinical trials particularly when more precise data regarding the radiobiological parameters and their statistical variations become available.

Humans↗
PubMed2000

Native and acid-denatured L-lactate dehydrogenase are different in the lysosomal proteinases involving in their overall degradation.

When native and (LDH) acid-denatured lactate dehydrogenase were incubated with total lysosomal enzymes in vitro, amino acids from their degradation were produced at various acidic pH. The pH profile in the overall degradation of native LDH was markedly different from that of acid-denatured LDH. Disappearance of the 35-kDa subunit of native LDH was markedly suppressed by a low level of cystatin alpha as well as by a general cysteine proteinase inhibitor, N-(L3-trans-carboxyoxirane-2-carbonyl)-L-leucine-3-methylbutylamid e (E-64-c). On the other hand, the degradation of acid-denatured LDH was only slightly suppressed by these inhibitors. It was concluded that at least a part of the proteinases involved in the overall degradation of native LDH is different from the proteinases involved in the degradation of acid-denatured form and a role of a cystatin alpha-sensitive cysteine proteinase is critical in the lysosomal degradation of native LDH, but not in that of acid-denatured form.

Cysteine Endopeptidases↗
PubMed2002

Correlation of vascular endothelial growth factor expression to overall survival in feline invasive mammary carcinomas.

Samples from feline invasive mammary carcinomas (FMCs) were used to determine the prognostic significance of the immunohistochemical expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD). Forty-eight queens bearing FMCs were included in a 2-year follow-up study. Mammary tumors were classified according to the World Health Organization system and graded on the basis of histologic criteria. Tumor sections were immunostained using anti-VEGF and anti-von Willebrand factor (vWf) antibodies. VEGF expression was quantified on the basis of the percentage of positive cells. MVD of vWf-positive microvessels was determined by both mean microvessel counts and highest microvessel counts. Normal mammary gland tissues showed an inconspicuous VEGF staining. In FMCs the proportion of VEGF-positive cells was significantly higher in papillary and solid carcinomas than in tubular and papillary cystic tumors. An increased number of cells expressing VEGF was also observed in poorly differentiated FMCS. Sixteen (33.3%) of the queens bearing invasive carcinomas were still alive at the end of the 2-year follow-up period, and 32 (66.7%) had died. The VEGF expression was significantly correlated with the clinical outcome, but no correlation was observed with the invasion of lymphatic vessels. A correlation between the higher percentage of VEGF-positive cells and the unfavorable prognosis was demonstrated by the estimation of curves for overall survival (P = 0.03). Univariate analysis showed that MVD did not correlate with the overall survival. The results of our study demonstrated that VEGF expression, although not associated with increased angiogenesis, is a prognostic indicator in feline mammary tumors. In contrast, there is no support for a role of neovascularization as an indicator of survivability.

Animals↗
PubMed2004

Overall coherence and coherent-mode expansion of spectrally partially coherent plane-wave pulses.

The modal theory for spectrally partially coherent nonstationary plane waves is introduced. The theory is first developed in the space-frequency domain and then extended to the space-time domain. Propagation properties of the coherent modes are analyzed. The concept of the overall degree of coherence is extended to the domain of nonstationary fields, and it is shown that the overall degree of coherence of partially coherent plane-wave pulses is the same in the space-frequency and space-time domains. The theory is applied to the recently introduced concept of spectrally Gaussian Schell-model plane-wave pulses.

Journal Article↗
PubMed2005

Implications of therapy choice on overall survival in metastatic renal cell carcinoma: a single institution experience.

PURPOSE: To compare the effect of high-dose interleukin-2 (HD IL-2) vs other cytokine therapies on 1-, 2, and 5-yr overall survival in patients with metastatic renal cell cancer (RCC). PATIENTS AND METHODS: We conducted a retrospective chart review of patients with untreated metastatic RCC treated by a single investigator. The different treatment groups included HD IL-2, low-dose IL-2 alone or in combination, interferon alpha alone and other therapies. The primary end point was survival from time of treatment. RESULTS: A total of 85 patients were studies with a median follow up of 13 mo (0.6-112.9). Median age at treatment was 59 yr with predominantly male patients and histology of clear cell type. Thirty-four percent received HD IL-2 and treatment was initiated less than 6 mo from the time of diagnosis in 66%. For all patients, median survival was 16 mo with a 5-yr survival of 12%. Two factors were good predictors of overall survival: Karnofsky performance status (KPS) of 100 (p < 0.0001) and soft tissue metastasis (p = 0.01). When comparing HD IL-2 to all other groups, median survival was 18 vs 14 mo and 1-yr survival was 74% vs 51%, respectively. CONCLUSION: HD IL-2 is associated with clinically meaningful improvement in median and 1-yr survival.

Carcinoma, Renal Cell↗
PubMed1987

The maximization of overall reinforcement rate on concurrent chains.

We model behavioral allocation on concurrent chains in which the initial links are independent variable-interval schedules. We also quantify the relationship between behavior during the initial links and the probability of entering a terminal link. The behavior that maximizes overall reinforcement rate is then considered and compared with published experimental data. Although all the trends in the data are predicted by rate maximization, there are considerable deviations from the predictions of rate maximization when reward magnitudes are unequal. We argue from our results that optimal allocation on concurrent chains, and prey choice as used in the theory of optimal diets, are distinct concepts. We show that the maximization of overall rate can lead to apparent violations of stochastic transitivity.

Journal Article↗
PubMed2000

Influence of research center on overall survival outcomes at each phase of treatment.

BACKGROUND: Clinical studies of dental implants tend to fall into two broad categories. Efficacy studies apply strict exclusion criteria under carefully controlled conditions to produce a narrow range of results. Effectiveness studies more closely model real-world treatment environments, with a more diverse patient sample and broader range of provider skills. In this multi-center study of more than 2,900 dental implants, study centers were grouped by implant survival scores in an attempt to draw attention to the influence of confounding variables associated with the treatment environment. METHODS: Thirty-two study centers were ranked by implant survival scores at uncovering and assigned to three performance groups. Centers whose overall scores were within approximately one standard deviation of the mean were placed in the middle (70%) performance group (MPG). The remaining centers were placed in either the top (15%) performance group (TPG) or the lower (15%) performance group (LPG). Overall survival and survival by phase of treatment were recorded for each of six implant designs in each of the three performance groups. RESULTS: From implant placement to 36 months, the TPG achieved survival rates from 100% (for 3 designs) to 95.5% (for one design), with an average of 97% for all designs. Increased variations in survival (97.2% to 73%) occurred in the MPG, with larger variations (96.4% to 48%) in the LPG. The HA-coated cylinder recorded consistently high survival scores (over 95%) in all performance groups and all phases of treatment. Failures for other designs in the MPG and LPG were concentrated in the healing period (placement to uncovering), except for the commercially pure titanium screw, which had the most failures between uncovering and prosthesis loading. CONCLUSIONS: Implant design and treatment environment both play an important role in implant survival. Two design characteristics appear to enhance survival: 1) a surgical protocol involving minimal instrumentation at placement, and 2) hydroxyapatite (HA) coating. The HA-coated press-fit cylinder design was the least affected by the center's performance.

Adult↗
PubMed2004

Body mass index, physical activity, and the risk of decline in overall health and physical functioning in late middle age.

OBJECTIVES: We examined the relation between body mass index, exercise, overall health, and physical functioning. METHODS: We studied 7867 adults aged 51 to 61 years in 1992 to 1996. Adjusted relative risks for health decline and new physical difficulties were determined with logistic regression. RESULTS: Overweight and obesity were independently associated with health decline (adjusted relative risk [ARR] = 1.29 and 1.36) and development of a new physical difficulty (ARR = 1.27 and 1.45). Regular exercise significantly reduced the risk of health decline and development of a new physical difficulty, even among obese individuals. CONCLUSIONS: Maintaining ideal body weight is important in preventing decline in overall health and physical functioning. However, regular exercise can reduce the risk of health decline even among individuals who cannot achieve ideal weight.

Attitude to Health↗
PubMed1983

An assessment of overall "gain" of the O2-feedback control system with and without external dead space breathing.

Overall gain of the O2-ventilation feedback control system (GO2) was determined in 9 male and one female healthy subjects. GO2 progressively increased with decreasing end-tidal PO2 (PETO2). This value did not exceed the overall gain of the CO2-ventilation feedback system (GCO2) even at a PETO2 level of 40 mmHg, suggesting that hypoxic stimulation did not become predominant in the present experimental condition. With addition of 250 ml of external dead space, PETO2 decrement (delta PETO2 X actual) was experimentally observed. The delta PETO2 X actual thus obtained was found to be in good agreement with the PETO2 decrement deduced from GO2 (delta PETO2 X expected). This result was similar to that found in the PETCO2 change previously seen in normoxia.

Adult↗
PubMed1985

An assessment of overall open-loop "gain" of CO2-ventilation feedback control system in hypoxia.

Overall open-loop gain of the CO2-ventilation feedback control system in hypoxia (GHCO2) was determined on 8 male and one female healthy subjects. They breathed in a closed circuit, and were subjected to the progressive hypoxia test. This procedure was first conducted without dead space (DS), then with 250, 500, and finally 750 ml DS, consecutively. GHCO2 was calculated by dividing the slope of the CO2 response curve (S) by that of the metabolic hyperbola (SL). GHCO2 was considerably larger than the overall open-loop gain of the O2-ventilation feedback control system (GO2) previously obtained. This was ascribed to the facts that S was larger than the slope of the hypoxia response curve, and that the absolute value of SL in GHCO2 was smaller than that in GO2.

Adult↗