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Biomedical subjects

R Livingston

Publications and source records attributed to R Livingston.

At least 19 recordsLinked to original sources
PubMed2006

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience.

BACKGROUND: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

Anemia↗
PubMed2004

Cell transplantation for treatment of acute myocardial infarction: unique capacity for repair by skeletal muscle satellite cells.

An adult heart injured by an ischemic episode has a limited capacity to regenerate. We administered three types of adult guinea pig cells [cardiomyocytes (CMs), cardiac fibroblasts (CFs), and skeletal myoblasts (Mbs)] to compare their suitability for repair of acute myocardial infarction. We used confocal fluorescent microscopy and a variety of specific immunomarkers and echocardiography to provide anatomic evidence for the viability of such cells and their possible functional beneficial effects. All cells were transfected with adenovirus-containing beta-galactosidase gene so that migration from the injection sites could be traced. Both freshly isolated CMs as well as CFs were found concentrated in the infarcted zone; these cells survived for at least 2 wk posttransplantation. Transplanted CMs were regularly striated and grew long projections that could form gap junctions with native CMs, which was evidenced by connexin43 labeling. In addition, CM transplantation resulted in increased angiogenesis in the infarcted areas. In contrast, transplanted CFs did not appear to make any gap junctional contacts with native CMs nor did they enhance local angiogenesis. Mbs cultured for 7 days and transfected Mbs were identified 7 days posttransplantation in the infarcted area. During that time and thereafter, Mbs proliferated and differentiated into myotubes that formed new, regularly striated myofibers that occupied most (50-70%) of the infarcted area by 2-3 wk. These newly formed myofibers maintained their Mb skeletal muscle origin as evidenced by their capacity to express myogenin and fast skeletal myosin. This skeletal phenotype appeared to downregulate with time, and Mbs partially transdifferentiated into a cardiac phenotype as indicated by labeling for cardiac-specific troponin T and cardiac myosin heavy chain. By the third week posttransplantation, new myofibers formed apparent contacts with the native CMs via putative gap junctions that expressed connexin43. Myocardial performance of animals that were successfully transplanted with Mbs was improved.

Age Factors↗
PubMed2002

Single-nucleotide polymorphisms and haplotype analysis in beta-defensin genes in different ethnic populations.

Beta-defensins are cationic antimicrobial peptides expressed by epithelial cells and exhibit antibacterial, antifungal, and antiviral properties. The defensins are part of the innate host defense network and may have a significant protective role in the oral cavity and other mucosa. Defects or alteration in expression of the beta-defensins may be associated with susceptibility to infection and mucosal disorders. We examined the occurrence of single-nucleotide polymorphisms (SNPs) in the human beta-defensin genes DEFB1 and DEFB2 encoding human beta-defensin-1 and -2 (hBD-1, hBD-2), respectively, in five ethnic populations and defined haplotypes in these populations. Fifteen SNPs were identified in both DEFB1 and DEFB2. Coding region SNPs were found in very low frequency in both genes. One nonsynonymous DEFB1 SNP, G1654A (Val --> Ile), and one nonsynonymous DEFB2 SNP, T2312A (Leu --> His), were identified. Seven sites in each gene exhibited statistically significant differences in frequency between ethnic groups, with the greatest variation in the promoter and in the 5'-untranslated region of DEFB1. DEFB1 displayed 10 common haplotypes, including one cosmopolitan haplotype. Eight common haplotypes were found in DEFB2, including one cosmopolitan haplotype shared among all five ethnic groups. Our results show that genotypic variability among ethnic groups will need to be addressed when performing associative genetic studies of innate defense mechanisms and susceptibility to disease.

Haplotypes↗
PubMed2001

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial.

BACKGROUND: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. METHODS: From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS: Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS: The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease.

Adult↗
PubMed2001

Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).

OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years. Recently, combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma. This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4 N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later. All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis. RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34 women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4 tumors. Induction therapy was completed as planned in 102 (92%) patients. There were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4 toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%) died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease. The 2-year survival was 55% for all eligible patients and 70% for patients who had a complete resection. To date, survival is not significantly influenced by patient sex, T status, or pathologic response. CONCLUSIONS: (1) This combined modality treatment is feasible in a multi-institutional setting; (2) the pathologic complete response rates were high; and (3) resectability and overall survival were improved compared with historical experience, especially for T4 tumors, which usually have a grim prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Increased false negative sentinel node biopsy rates after preoperative chemotherapy for invasive breast carcinoma.

BACKGROUND: Sentinel lymph node dissection (SLND) has been a promising new technique in breast carcinoma staging, but could be unreliable in certain patient subsets. The current study assessed whether age, preoperative chemotherapy, tumor size, and/or previous excisional biopsy influenced the identification of sentinel nodes (SLNs) or the reliability of a node-negative SLND in predicting a node negative axilla. METHODS: Eighty-two patients who had clinically negative axillae underwent SLND followed by Level I/II axillary lymph node dissection (ALND). SLNDs were performed using both technetium-99m (Tc-99m) labeled colloid and isosulfan blue dye. SLNs were analyzed by hematoxlyin and eosin and immunocytochemical techniques. RESULTS: SLNs were successfully identified in 80% of patients. Mapping success was decreased among postmenopausal women but was not influenced by preoperative chemotherapy, large tumor size, or previous excisional biopsy. Of the 31 successfully mapped, node positive patients, 5 had false negative (FN) SLNDs (overall FN rate = 16%). Of the 9 successfully mapped patients who had received preoperative chemotherapy and had positive axillary nodes, 3 had FN SLND (FN rate = 33%). The presence of clinically positive lymph nodes before chemotherapy did not predict which patients would have a subsequent FN SLND. T3 tumor size, but not previous excision, was associated significantly with increased FN rate, although the FN rate for previous excision was 11%. No FN SLND occurred with T1/T2 tumors that were not excised previously and had not received preoperative chemotherapy. CONCLUSIONS: Preoperative chemotherapy was associated with an unacceptably high FN rate for SLND. While larger tumor size also was associated with FN SLND, this effect might have been due to preoperative chemotherapy use in these patients. Small sample size precluded determining whether excisional biopsy before mapping increased FN SLND rates independently.

Adult↗
PubMed2000

Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine+rapamycin regimen.

BACKGROUND: Clinically, cyclosporine (CSA, Neoral) is titrated to concentrations, and not to pharmacological effect. METHODS: Intracellular interleukin- (IL) 2 was measured in phorbol myristic acid-ionomycin-stimulated peripheral lymphocytes by flow cytometry, after isolation from 14 renal transplant recipients receiving CSA+prednisone, and double-blind rapamycin (rapamycin:placebo=4:1). RESULTS: The proportion (%) of CD4+IL-2+ lymphocytes corresponding to CSA levels (mean+/-SD ng/ml) measured preoperatively (TO=O), and on postoperative day 8, before (356+/-63), and 2 hr after the morning dose (Cmax=1567+/-669), decreased from 39+/-16 to 15+/-8 and 3+/-1.6, respectively. Reciprocally, unresponsive lymphocytes (%CD4+IL-2-) increased with increasing CSA levels and predicted an EC50 of 249 ng/ml (CSA concentration at which CD4+IL-2- cells increased by 50% over baseline) in an Emax pharmacodynamic model. CONCLUSIONS: Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.

CD4-Positive T-Lymphocytes↗
PubMed2000

Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.

STUDY OBJECTIVES: The purpose of this phase III clinical trial was to test whether chemotherapy followed by radiation therapy resulted in superior survival to either hyperfractionated radiation or standard radiation in surgically unresectable non-small cell lung cancer. DESIGN: Patients were prospectively randomized to 2 months of cisplatin, vinblastine chemotherapy followed by 60 Gy of radiation at 2.0 Gy per fraction or 1.2 Gy per fraction radiation delivered twice daily to a total dose of 69.6 Gy, or 2.0 Gy per fraction of radiation once daily to 60 Gy. Patients were enrolled from January 1989 through January 1992, and followed for a potential minimum period of 5 years. SETTING: This trial was an intergroup National Cancer Institute-funded trial within the Radiation Therapy Oncology Group, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group. PATIENTS: Patients with surgically unresectable non-small cell lung cancer, clinical stage II, IIIA, and IIIB, were required to have a Karnofsky Performance Status of > or = 70 and a weight loss of < 5% for 3 months before study entry. Four hundred ninety patients were registered on trial, of which 458 patients were eligible. CONCLUSION: Overall survival was statistically superior for the patients receiving chemotherapy and radiation vs the other two arms of the study. The twice-daily radiation therapy arm, although better, was not statistically superior in survival for those patients receiving standard radiation. Median survival for standard radiation was 11.4 months; for chemotherapy and irradiation, 13.2 months; and for hyperfractionated irradiation, 12 months. The respective 5-year survivals were 5% for standard radiation therapy, 8% for chemotherapy followed by radiation therapy, and 6% for hyperfractionated irradiation.

Adult↗
PubMed1999

Possible interactions between dietary antioxidants and chemotherapy.

Many patients treat themselves with oral antioxidants and other alternative therapies during chemotherapy, frequently without advising their conventional health care provider. No definitive studies have demonstrated the long-term effects of combining chemotherapeutic agents and oral antioxidants in humans. However, there is sufficient understanding of the mechanisms of action of both chemotherapeutic agents and antioxidants to predict the obvious interactions and to suggest where caution should be exercised with respect to both clinical decisions and study interpretation. This article will describe these potential interactions and areas of concern, based on the available data. It will also suggest several potential courses of action that clinicians may take when patients indicate that they are taking or plan to use alternative therapies.

Administration, Oral↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1997

Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial.

PURPOSE: To determine the response rate of cisplatin plus doxorubicin plus cyclophosphamide (PAC) in patients with limited-stage unresectable thymoma. In addition, this study was undertaken to determine the toxicity, progression-free survival, and overall survival of combined-modality therapy with PAC plus radiation therapy. PATIENTS AND METHODS: Patients with a histologic diagnosis of limited-stage unresectable thymoma or thymic carcinoma were eligible. Further requirements included a Karnofsky Performance Score of > 60, no prior radiation to the chest, and adequate bone marrow, hepatic, and renal function. No patient had undergone chemotherapy previously. Patients received two to four cycles (repeated every 3 weeks) of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) followed by a total dosage of 54 Gy to the primary tumor and regional lymph nodes for patients with a stable, partial, or complete response to chemotherapy. RESULTS: From November 1983 through January 1995, 26 patients were entered onto the trial. Three patients were ineligible on the basis of pathologic review (lung cancer, germ cell cancer, lymphoma). Toxicity, primarily hematologic, was mild, with only one early death due to a perforated abdominal viscus. Among the 23 assessable patients, there were five complete and 11 partial responses to chemotherapy (overall response rate, 69.6%). The median time to treatment failure was 93.2 months (range, 3 to 99.2+ months), and the median survival time was 93 months (range, 1 to 110 months). The 5-year survival rate is 52.5%. CONCLUSIONS: PAC combination chemotherapy produces response rates in the management of patients with limited thymoma. Combined-modality therapy is feasible and associated with prolonged progressive-free survival. The benefit of combined-modality therapy over radiation therapy alone is suggested for patients with unresectable thymoma.

Adult↗
PubMed1996

Abnormal microenvironmental signals underlie intestinal aganglionosis in Dominant megacolon mutant mice.

Dominant megacolon (Dom) is a mutation in an uncharacterized murine gene which is associated with intestinal aganglionosis and the focal absence of melanocytes in heterozygous animals. The phenotype of Dom/+ heterozygotes is similar to the lethal spotted and piebald lethal mutations, which are due to defects in endothelin-mediated intercellular signals. In this study, the DbetaH-nlacZ transgenic marker for enteric neural crest cells is used to study the distribution of enteric neurons and their precursors in Dom/+ mice and embryos. Vagal neural crest-derived cells in wild-type embryos colonize the gut in a cranial-to-caudal progression. In Dom/+ embryos, colonization was retarded from the earliest stages examined (embryonic Day 11.0), including progression through the small intestine. The early onset of this defect contrasts with impaired neural crest colonization associated with the lethal spotted and piebald lethal mutations which manifest only in the large intestine. Analysis of Dom/+ - +/+ aggregation chimeras indicated that defective colonization is not an autonomous (intrinsic) property of Dom/+ neuroblasts, but like lethal spotted and piebald lethal, the Dominant megacolon mutation directly or indirectly affects microenvironmental signals which influence the migration, proliferation, and/or survival of enteric neural crest cells.

Animals↗
PubMed1995

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.

Adult↗
PubMed1995

An automated electronic method for quantifying spinning (circling) in children with autistic disorder.

This pilot study examined and quantified rotational asymmetry (the tendency to turn preferentially to the right or left side). An automated device was used to measure turning (circling) in 9 children with autism and 27 normal control subjects and confirmed clinical observations of stereotypical spinning behavior in patients with autism. This behavior was significantly preferential toward the left side relative to control subjects (P = 0.0009, two-tailed). Group membership accounted for approximately 40% of variance. Although the precise causes of autism are not known, these preliminary data suggest that the spinning behavior often seen in children with neurodevelopmental disorders can be reliably measured. Furthermore, spinning in autism may most often manifest as specific right-hemispace neglect.

Arousal↗