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Biomedical subjects

William Miller

Publications and source records attributed to William Miller.

28 records · Page 2Linked to original sources
PubMed2004

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8+ T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients.

Antigens, Neoplasm↗
PubMed2004

Self-reported delay in seeking care has poor validity for predicting adverse outcomes.

OBJECTIVES: To determine whether self-reports of delayed care predict increased mortality and functional decline in community-dwelling elderly. DESIGN: Longitudinal cohort study. SETTING: Five counties in North Carolina. PARTICIPANTS: A total of 4,162 randomly sampled individuals aged 65 and older. MEASUREMENTS: The primary outcome was the proportional hazard ratio (HR) for death in cohorts stratified by self-reports of delayed or foregone care. A secondary outcome, functional decline, measured the cohorts' odds of developing increased dependency in activities of daily living (ADLs). Control variables included predisposing, enabling, and need factors. RESULTS: Of 3,964 eligible participants reporting, 61% never, 27% once in a while, and 12% quite often delayed care. Over 3 years, 13% of participants died, and 17% developed increased ADL dependency. Nevertheless, in unadjusted and adjusted models, neither 3-year mortality HRs nor the odds of functional decline differed between cohorts reporting varying degrees of delayed care. Survival probabilities remained higher for 15 years among those reporting delaying care often. CONCLUSION: The inability of self-reported delay to predict adverse outcomes in community-dwelling elderly suggests the need for better understanding and support of the care-seeking process and additional measures of timeliness of access.

Activities of Daily Living↗
PubMed2004

Fate of salmonellae in orange and grapefruit concentrates during cold storage.

Orange and grapefruit concentrates at 42, 50, and 64 degreesBrix were inoculated with a five-strain cocktail of acid-adapted salmonellae stored at 0, -5, -10, -15, or -20 degrees C and sampled for population survival up to 11 and 50 days for grapefruit and orange concentrates, respectively. Survivor curves were nonlinear and best fit by a three-parameter power equation: Y = a + bXc. Final log reductions ranged from 2.3 to 4.8 after 50 days in orange concentrate and 6.0 to 6.9 after 11 days in grapefruit concentrate. Storage times needed to achieve a 5-log population reduction among all treatments for grapefruit concentrate ranged from 1.0 to 5.8 days. Significant differences (P < or = 0.05) were observed among results for different temperatures within any single Brix level; however, storage times among Brix levels at any one temperature were not significantly (P < or = 0.05) different. Results indicate that cold storage of grapefruit concentrate is a viable treatment for achieving a 5-log reduction in salmonellae.

Beverages↗
PubMed2004

Kidney transplantation from organ donors following cardiopulmonary death using extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) has the ability to provide normal organ perfusion and oxygenation in the absence of cardiac function and thus has the potential to improve viability of subsequently transplanted kidneys. In addition, ECMO support allows the donation following cardiopulmonary death (DCD) process to occur in a controlled manner that is acceptable to staff unfamiliar with DCD. In 1999 our center implemented a controlled DCD program that incorporates post-mortem ECMO support of the organs. Arterial and venous cannulae are placed following consent to donate, but prior to withdrawal of support. ECMO circulation is initiated immediately following declaration of death. Following a brief period where the donor family is allowed to grieve, the donor is moved to the operating room where organ recovery occurs. We reviewed the results of 20 kidney transplants from 13 ECMO supported donors that occurred between October 2000 and August 2003. One renal allograft was lost due to surgical complications, all 19 remaining grafts functioned. An 11% (2/19) delayed graft function rate was observed. Kidneys donated from "controlled" ECMO supported CPD donors are a viable source of organs for renal transplantation. This recovery method warrants further investigation.

Cadaver↗
PubMed2002

Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer.

PURPOSE: This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with unresectable or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients received repeated 21-day cycles at starting doses of gemcitabine 1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety. RESULTS: Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95% confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9 decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%). Median TTP was 2.8 months (range, 0.3 to 10.8 months). There were significant (P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor area with regard to extent of change (r =.67), timing of minimum on-study values (r =.85), and tumor progression (r =.89). Median survival was 5.7 months (range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%). CONCLUSION: Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-intensity.

Adult↗
PubMed2002

Reliability and validity of the Leisure Satisfaction Scale (LSS--short form) and the Adolescent Leisure Interest Profile (ALIP).

This study aimed to evaluate the reliability and validity of the Leisure Satisfaction Scale (LSS short form) and the Adolescent Leisure Interest Profile (ALIP). The LSS and the ALIP are instruments that occupational therapists can use to evaluate the leisure activities that clients enjoy. Evaluation of leisure interest and participation will assist in creating goals for therapy to maximize a client's ability to participate in leisure activities. This study examined the test retest reliability and concurrent validity of the LSS and the ALIP using a sample of 37 adolescents between the ages of 13 and 17 with no known impairments. The assessments were administered individually or in small groups 7 to 17 days apart. Cronbach's alpha was used to determine the internal consistency. Pearson product moment correlations were calculated to examine the test retest reliability of the 60 subscales and the six question totals of the ALIP, as well as for the 6 subscales and total score of the LSS. Concurrent validity was evaluated between the 'How often?' question of the ALIP and the LSS (short form). Based on the study results, the ALIP and the LSS seem to have good test retest reliability levels when used with adolescents with no known physical or mental impairments. The concurrent validity between the two instruments was not supported, with many of the scores indicating only weak or no association to each of the subscales, suggesting that the assessments differ in some fundamental way. However, the evidence of some relationships between subscales may indicate some areas where the ALIP and the LSS are similar.

Adolescent↗
PubMedDate not supplied

Severe jaundice in a patient with a previously undescribed glucose-6-phosphate dehydrogenase (G6PD) mutation and Gilbert syndrome.

A patient with chronic hemolytic anemia and G6PD deficiency was noted to be severely jaundiced and to have a high serum ferritin level. Analysis of his DNA revealed only heterozygosity for the c.187 C-->G (H63D) mutation of HFE, but showed that he was homozygous for the UDP glucuronosyltransferase promoter mutation of Gilbert's disease and that he had a previously undescribed mutation of G6PD, c.832 T-->C (Ser278Pro). The new variant was named G6PD La Jolla.

Adult↗