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Biomedical subjects

B L Roberts

Publications and source records attributed to B L Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma.

Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy. A second generation E1/E4 region deleted Ad which harbors the CMV immediate-early promoter/enhancer and a unique E4-ORF6/pIX chimeric gene was employed as the backbone vector. We demonstrate that human monocyte-derived DC are permissive to Ad infection at multiplicity of infection between 100 and 500 and occurs independent of the coxsackie Ad receptor. Fluorescent-labeled Ad was used to assess the kinetics and distribution of viral vector within DC. Ad-transduced DC show peak transgene expression at 24-48 h and expression remains detectable for at least 7 days. DC transduced with replication-deficient Ad do not exhibit any unusual phenotypic characteristics or cytopathic effects. DC transduced with Ad2/gp100v2 can elicit tumor-specific CTL in vitro from patients bearing gp100+ metastatic melanoma. Using a panel of gp100-derived synthetic peptides, we show that Ad2/gp100v2-transduced DC elicit Ag-specific CTL that recognize only the G209 and G280 epitopes, both of which display relatively short half-lives ( approximately 7-8 h) on the surface of HLA-A*0201+ cells. Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8+ T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes.

Adenoviruses, Human↗
PubMed2000

Immunogene therapy for murine melanoma using recombinant adenoviral vectors expressing melanoma-associated antigens.

Adenoviral vectors expressing tumor-associated antigens can be used to evoke a specific immune response and inhibit tumor growth. In this study, we tested the efficacy of adenoviral vectors encoding human gp100 (Ad2/hugp100), murine gp100 (Ad2/mugp100), or murine TRP-2 (Ad2/muTRP-2) for their ability to elicit a specific cellular immune response and inhibit the growth of B16 melanoma tumor cells in the mouse. C57BL/6 mice were immunized with Ad2/hugp100, Ad2/mugp100, or Ad2/muTRP-2 either 2 weeks prior to B16-F10 tumor challenge (prophylactic treatment) or 3 days after tumor challenge (active treatment). Ad2/hugp100 and Ad2/muTRP-2 administered to two or more intradermal (i.d.) sites inhibited subsequent subcutaneous tumor growth in > or = 80% of the mice and elicited an antigen-specific cytotoxic T lymphocyte response, whereas other administration routes were not as effective. Ad2/mugp100 administered to two i.d. sites did not inhibit tumor growth or provoke cellular immunity. Immunization was less effective with active treatment where tumor growth was not significantly inhibited by a single dose of either Ad2/muTRP-2 or Ad2/hugp100. However, increasing the number of intradermal immunization sites and the number of doses resulted in progressive improvements in protection from tumor growth in the active treatment model. In conclusion, breaking host tolerance to elicit protective immunity by using adenoviral vectors expressing melanoma-associated antigens is dependent upon the choice of antigen, the site of administration, and the number of doses. These observations provide insights into the clinical applicability of adenoviral vaccines for immunotherapy of malignant diseases.

Adenoviridae↗
PubMed2000

Social support and strain of family caregivers of older adults.

To assess the direct effects and interactive models of social support, caregivers to functionally impaired older adults were identified by hospital personnel. Within a week of referral, family caregivers were interviewed in the home about strain, depressive symptomatology, caregiving appraisal, informal social support, and coping. Caregiving appraisal significantly explained strain and depressive symptomatology. The interaction of social support with strain did not moderate or lessen depressive symptomatology. These findings suggest that nursing continue to examine the effect of home health care on strain and depressive symptomatology of caregivers of older adults.

Adaptation, Psychological↗
PubMed2000

Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS.

STUDY OBJECTIVES: This study was carried out to determine the efficacy of and dose-response relationships to inhaled aerosolized prostacyclin (IAP), when used as a selective pulmonary vasodilator (SPV) in patients with severe hypoxemia due to ARDS. DESIGN: Unblinded, interventional, prospective clinical study. SETTING: A general ICU in a university-affiliated, tertiary referral center. PATIENTS: Nine adult patients with severe ARDS (lung injury score, > or = 2.5). INTERVENTIONS: All patients received IAP over the dose range 0 to 50 ng/kg/min. The IAP was delivered via a jet nebulizer placed in the ventilator circuit. Dose increments were 10 ng/kg/min every 30 min. MEASUREMENTS AND RESULTS: Cardiovascular parameters (cardiac index and mean pulmonary and systemic pressures), indexes of oxygenation (PaO(2)/fraction of inspired oxygen [FIO(2)] ratio and alveolar-arterial oxygen partial pressure difference [P(A-a)O(2)]) and shunt fraction were measured or calculated at each dose interval, as were platelet aggregation and systemic levels of prostacyclin metabolite (6-keto prostaglandin F1(alpha)). A generalized linear regression model was used to determine a dose effect of IAP on these parameters. The Wilcoxon rank sum test for related measures was used to compare the effects of various doses of IAP. IAP acted as an SPV, with a statistically significant dose-related improvement in PaO(2)/FIO(2) ratio (p = 0.003) and P(A-a)O(2) (p = 0.01). Systemic prostacyclin metabolite levels increased significantly in response to delivered IAP (p = 0.001). There was no significant dose effect on systemic or pulmonary arterial pressures, or on platelet function, as determined by platelet aggregation in response to challenge with adenosine diphosphate. CONCLUSIONS: IAP is an efficacious SPV, with marked dose-related improvement in oxygenation and with no demonstrable effect on systemic arterial pressures over the dose range 0 to 50 ng/kg/min. Despite significant systemic levels of prostacyclin metabolite, there was no demonstrable platelet function defect.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial.

The purpose of this Phase I study was to determine the feasibility of using an anti-erbB-2-encoding adenovirus (Ad21) to treat erbB-2-overexpressing ovarian cancer. Recurrent ovarian cancer patients were treated i.p. with Ad21 in dosages ranging from 1 x 10(9) to 1 x 10(11) pfu. Patients were monitored after treatment for evidence of clinical toxicity and efficacy. Peritoneal aspirates and serum samples were obtained to assess for evidence of gene transfer/expression, for generation of wild-type vector, and antiadenoviral humoral response. Fifteen patients were treated per study specifications. Treatment-specific grade 1/2 fever was experienced by 9 of 15 (60%) patients. Other transient grade 1/2 constitutional, pain, and gastrointestinal symptoms were also experienced. No dose-limiting vector-related toxicity was experienced. Of 13 patients evaluable for response, 5 (38%) had stable disease and 8 (61%) had evidence of progressive disease. One patient with nonmeasurable disease normalized her CA125 at the 8-week evaluation, and one patient with nonmeasurable disease remained without clinical evidence of disease for 6 months after treatment. PCR analysis of peritoneal aspirates demonstrated the presence of Ad21 in 84.6%, 84.6%, and 61.6% of evaluable specimens at days 2, 14, and 56 after treatment, respectively. No wild-type virus was detected. Reverse transcription-PCR analysis demonstrated expression of the anti-erbB-2 sFv-encoding gene in 10 of 14 evaluable patients at day 2. Five of six evaluable patients had an increase in antiadenovirus antibody titer. This study suggests that adenoviral-mediated gene therapy using an anti-erbB-2-directed intrabody is feasible in the context of human ovarian cancer.

Adenoviruses, Human↗
PubMed1999

Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens.

Dendritic cells (DCs) are professional Ag-presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor Ags. In this study, recombinant adenovirus (Ad) vectors encoding melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and induce protective immunity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad vector encoding the hugp100 melanoma Ag (Ad2/hugp100) elicited the development of gp100-specific CTLs capable of lysing syngeneic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100. The induction of gp100-specific CTLs was associated with long term protection against lethal s.c. challenge with B16 cells. It was also possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced with Ad vector encoding the Ag. The level of antitumor protection achieved was dependent on the dose of DCs and required CD4+ T cell activity. Importantly, immunization with Ad vector-transduced DCs was not impaired in mice that had been preimmunized against Ad to mimic the immune status of the general human population. Finally, DC-based immunization also afforded partial protection against established B16 tumor cells, and the inhibition of tumor growth was improved by simultaneous immunization against two melanoma-associated Ags as opposed to either one alone. Taken together, these results support the concept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags.

Adenoviridae↗
PubMed1997

Pharmacist influence on economic and morbidity outcomes in a tertiary care teaching hospital.

The influence of pharmacist participation on economic and morbidity outcomes at a tertiary care teaching hospital was studied. Patients admitted to internal medicine wards during a nine-month period were assigned to either a treatment team or a control team. Each team consisted of an attending physician, senior and junior medical residents, and medical students; the treatment team included a pharmacist who reviewed all patient charts, made rounds with the team, and recommended modifications of drug therapy. Pharmacy interaction with the control team was limited to contacting physicians about potentially dangerous orders, answering questions from the medical team, and handling orders for items not on the formulary or otherwise unavailable. After discharge, data from patient records were analyzed for pharmacy costs and total hospital costs and length of stay (as markers of the pharmacist's effect on economics and morbidity, respectively). Analysis of baseline characteristics showed that the two groups of patients were statistically comparable. Treatment team patients who were included in the data analysis (414) had significantly shorter stays (by a mean of 1.3 days) and lower pharmacy and total hospital costs (by a mean of $301 and $1654, respectively) than those included in the control team analysis (453). The direct participation of a pharmacist on a patient care team significantly decreased pharmacy and hospital costs, as well as length of stay, compared with minimal participation of a pharmacist.

Analysis of Variance↗
PubMed1997

Soft tissue manipulation: neuromuscular and muscle energy techniques.

Muscle rigidity and spasms occur with neurological disease and may contribute to contractures and shortening of muscle fibers that can interfere with motor behaviors, such as ambulation, or activities of daily living, such as combing hair, feeding or dressing. The neuromuscular technique (NMT) and muscle energy technique (MET) are nursing interventions that can reduce pain and muscle rigidity, lengthen muscle fibers and increase range of motion necessary for normal motor behavior. Nurses can use these techniques in patients with acute neurological diseases and those recovering in rehabilitation and long-term care settings. With some neurological diseases, muscle rigidity, increased muscle tone and muscle spasms reduce the range of motion of joints and the quality of movement. These changes often lead to contractures and impairments in performing daily tasks or ambulating, and thus, to loss of independence. Soft tissue manipulation can be used to reduce muscle tension and spasms, reduce pain and enhance the range of motion of joints whose function depends on the involved muscles. Soft tissue manipulation may also improve movement during specific tasks. Although the muscle relaxation achieved with manipulation techniques is primarily short-term, long-term effects occur. This article describes two techniques of soft tissue manipulation, their mechanisms of action, assessment and implementation. A case study is used to illustrate application of the techniques and possible long-term effects.

Aged↗
PubMed1997

Infection in central lines: antiseptic-impregnated vs standard non-impregnated catheters.

We report a survey of 196 consecutive central venous catheters (CVCs) placed in 151 patients in the Intensive Care Unit (ICU) over a ten-month period. Over this time the use of a new antiseptic-impregnated triple lumen CVC (Arrowgard Blue, Arrow International Inc., Pennsylvania, U.S.A.) was alternated on a bimonthly basis with the standard triple-lumen CVC (Arrow International Inc., Pennsylvania, U.S.A.). The overall rate of CVC tip infection was lower in the impregnated CVC group (15.6% vs 30.9%, P < 0.05). The impregnated CVC group had a much lower cumulative infection rate when the dwell time in patients was five days or less (3.3% vs 26.9%, P < 0.05). However, the difference between the cumulative infection rate was not statistically significant (P > 0.05) for dwell times of 6, 7 or 8 days respectively. There was no difference in the CVC related bacteraemia rates between the two groups (3.9% vs 3.7%, P > 0.05).

Adolescent↗
PubMed1996

Theoretical and psychometric analysis of caregiver strain.

The purpose of the study was to establish the validity and reliability of an instrument for the measurement of caregiver strain, the Parent Caregiver Strain Questionnaire (PCSQ), with data from 283 adult children who were providing care to a neurologically impaired patient. Principal axis factor analysis of data rotated to an oblimin solution revealed five well-defined, first-order factors that explained 59% of the total variance in caregiver strain. The five-factors were interrelated with caregiver strain as theoretically predicted. Coefficient alphas for the five factors were in the range from .74 to .93. The findings provide beginning evidence of the adequacy of the PCSQ, and favor continued investigation into the theoretical and psychometric properties of the instrument.

Aged↗
PubMed1996

The effects of social support on the relationship of functional limitations and pain to depression.

OBJECTIVE: This study assessed the effects of social support on the relationship of functional impairments and pain to depression. METHODS: Fifty-nine persons with end-stage joint disease (27 men and 32 women with an average age of 65 years) were interviewed. The Arthritis Impact Measurement Scales (AIMS) was used to assess functional impairment and depression. The modified Inventory of Socially Supportive Behaviors was used to assess 4 types of social support (emotional, informational, tangible, and integrative). RESULTS: Contrary to the moderator model of social support, only low tangible support attenuated the adverse effects of functional impairments on depression, while other levels of this type and 3 other types of support either had no effect or enhanced the deleterious effects of functional impairments. Social support did not attenuate the relationship between pain and depression. DISCUSSION: The findings suggest that certain types and levels of social support may reduce the effects of functional limitation and pain on depression, while other types and levels may increase their adverse effects.

Activities of Daily Living↗
PubMed1996

Changes in enzyme histochemical profiles of identified spinal motoneurons of the European eel, Anguilla anguilla, following cordotomy.

The enzyme histochemical profiles of glucose-6-phosphate dehydrogenase (a marker of synthetic performance), succinate dehydrogenase (an indicator of oxidative metabolism), and NADH tetrazolium reductase (a marker of overall neuronal activity) were determined for identified white muscle motoneurons in six control and six cordotomized cels. Images were digitized and mean integrated absorbances obtained using appropriate hardware and software. For motoneurons caudal to the transection site there was a significant decrease in the mean absorbance value for NADH tetrazolium reductases which declines from 0.28 a.u. (arbitrary units) in control animals to 0.23 a.u. in cordotomized animals. However, no significant changes were detected in the activities of glucose-6-phosphate and succinate dehydrogenases. The cross-sectional area of the motoneuronal cell body was not affected by cordotomy. The decrease by around 20% in overall neuronal activity, as expressed by NADH tetrazolium reductase activity, might be expected from the decline in body motility that follows cordotomy. Changes in SDH and G6PDH activities would also be expected to follow this surgery, but none were seen, perhaps because they are compensated for by changes in neuronal metabolism that result from deafferentation.

Anguilla↗
PubMed1996

Affinity maturation of proteins displayed on surface of M13 bacteriophage as major coat protein fusions.

This chapter described the preparation and fractionation of libraries of M13 phage displaying proteins as fusions to the major coat protein. High titer (10(13) pfu/ml) phage libraries can readily be generated using a single vector and the level of display surpasses that of gene III fusion phage. Since the synthetic VIII fusion gene can be customized, this system should provide the flexibility required to construct phage libraries displaying a variety of different peptides and proteins and to select variants possessing the highest affinity for target molecules of a diverse chemical nature.

Bacteriophage M13↗
PubMed1996

Central venous catheters revisited--infection rates and an assessment of the new Fibrin Analysing System brush.

Sixty-one consecutive patients in the Intensive Care Unit requiring central venous lines (CVC) for five or more days were randomized to receive either a standard triple lumen CVC (STD/CVC) or a silver sulphadiazine and chlorhexidine impregnated CVC (SSD/CVC). Data from the 54 patients who completed the trial show a reduced infection rate (positive tip culture) in the SSD/CVC group (4 out of 28) compared to the STD/CVC group (10 out of 26) (P < 0.05). In addition, the new Fibrin Analysing System (FAS) brush was evaluated and used to determine the presence of infection in all the CVCs (STD/CVC and SSD/CVC combined, n = 54) at day 3 (i.e. early warning of CVC colonization/infection) and at the time of removal of the CVC. The FAS brush was able to detect an infected CVC on only one occasion on day 3 out of the 14 CVC tips which were later found to be colonized/infected at the time of removal. The sensitivity of the FAS brush in detecting colonized/infected CVCs at the time of CVC removal compared with CVC tip culture was 21% with a specificity of 100%. These findings would currently not support the routine use of the FAS brush in determining CVC infection/colonization.

Acinetobacter↗
PubMed1996

Cardiac response of elderly adults to normal activities and aerobic walking.

To assess the cardiac response of elderly adults, three sedentary men and six women (M = 68 years) with no known cardiovascular disease had their cardiac responses to activities done in a laboratory setting (walking, climbing stairs, carrying bags, shuffleboard); normal daily activities and aerobic walking (pace at 60% of the age-adjusted heart rate) were assessed by a 24-hour holter monitor. Supraventricular and ventricular ectopies were common during the 24 hours of monitoring, but none occurred during any of the activities. Bradycardia occurred at night, along with some supraventricular and ventricular ectopy, none clinically significant. Heart rate increased as the intensity of the activity increased (e.g., 68/ minute for carrying 5 pounds of groceries to 90/ minute during aerobic walking). When prescribing exercise or activity limitations, the chronotropic effects of usual daily activities must be considered in counseling sedentary, apparently healthy older adults.

Activities of Daily Living↗