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Biomedical subjects

R L Evans

Publications and source records attributed to R L Evans.

At least 19 recordsLinked to original sources

The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules.

CD19 is a member of the Ig superfamily expressed on the surface of B lymphocytes that may be involved in the regulation of B cell function. Immunoprecipitation studies with B cell lines solubilized by digitonin have shown CD19 to be part of a multimolecular complex that includes CD21 (CR2) and other unidentified proteins. In this study, two of the CD19-associated proteins were identified as TAPA-1, which is expressed on most cell types, and Leu-13, which is expressed on subsets of lymphoid cells. TAPA-1 and Leu-13 are physically associated in many cell lineages. CD19 and CD21 mAb each specifically coprecipitated proteins of the same size as those precipitated by TAPA-1 and Leu-13 mAb from B cell lines and cDNA-transfected K562 cell lines. Western blot analysis with a TAPA-1 mAb verified the identity of TAPA-1 in CD19 and CD21 immunoprecipitated materials. In addition, when TAPA-1 or Leu-13 were crosslinked and patched on the cell surface, all of the CD19 comigrated with TAPA-1 and some of the CD19 comigrated with Leu-13. Furthermore, mAb binding to CD19, CD21, TAPA-1, and Leu-13 on B cell lines induced similar biologic responses, including the induction of homotypic adhesion, inhibition of proliferation, and an augmentation of the increase in intracellular [Ca2+] induced by suboptimal cross-linking of surface Ig on B cell lines. Together, these data suggest that TAPA-1 and Leu-13 are broadly expressed members of a signal transduction complex in which lineage-specific proteins, such as CD19 and CD21, provide cell-specific functions.

Antigens, CD

Research in social work practice: benefits of and obstacles to implementation in the Department of Veterans Affairs.

Although research is an important part of social work practice in health care, there is little systematic information that sheds light on research productivity, the benefits of conducting research, or the obstacles that must be overcome. This article represents the viewpoints of nearly all the directors of social services departments in the largest multihospital system in the United States, the Department of Veterans Affairs. The organizational characteristics of hospitals and the attitudes of the directors about research were important correlates of research productivity. Although lack of time, resources, and interest were cited as common obstacles, more than one-third of the departments were conducting or involved in at least one study. Information about the research efforts of other social services departments was considered an important resource, particularly for departments with no ongoing studies. The implications of these findings for social work research in health care are discussed.

Attitude

The family's role in stroke rehabilitation. A review of the literature.

Clinical and research attention in stroke care has been on managing the acute stage of stroke recovery and on evaluating the effectiveness of relatively short-term rehabilitation programs. However, studies suggest that stroke can diminish quality of life and the well-being of patients' families. This article reviews the literature pertaining to the effects of stroke on family functioning and discusses stroke in terms of clinical problems that make rehabilitation a family dilemma. Issues identified in the literature include the need for family assessment, education, advocacy and counseling to foster treatment compliance and social support after stroke.

Adaptation, Psychological

Providing care to persons with physical disability. Effect on family caregivers.

Studies on caregiving often assume that outcomes will be problematic and assess negative factors, such as burden or stress. Results may be biased by detailing only the problems encountered. The current study assessed positive, neutral and negative aspects of caregiving and evaluated the impact of caregiving using criteria based on an accepted model of family functioning. Of 942 consecutive hospital admissions, 217 subjects required assistance in personal care and returned home with a primary caregiver. Caregivers reported moderately more anxious, depressive and somatic symptoms than expected from standardized tests, but these findings were not clinically or statistically significant. Family functioning was related to the duration of the caregiving experience. Family relations seemed to be a source of strength for caregivers, regardless of disability type. Further research is needed to determine if family functioning can be used to buffer against unfavorable aspects of caregiving or to enhance positive aspects of the situation.

Activities of Daily Living

Differential modulation of the CD-2 and CD-3 T cell activation pathways by a monoclonal antibody to Leu-13.

MAb anti-Leu-13 reacts with a 16-kDa-interferon-responsive lymphocyte-endothelial cell surface antigen and has been demonstrated to induce lymphocyte aggregation by an undefined adhesion pathway. While anti-Leu-13 inhibits proliferation triggered by CD3 antibodies it was found to consistently augment proliferation induced by a pair of CD2 antibodies at suboptimally mitogenic concentrations. The latter mechanism of T cell activation may represent an antigen-nonspecific activation pathway requiring extensive cell-cell interaction. Proliferation induced via the CD2 pathway was very sensitive to the presence of monocytes whose inhibitory effect was reversed by indomethacin. While the potent inhibitory effect of PGE2 on proliferation induced via the CD2 pathway was weakly antagonized by anti-Leu-13, the combined effects of anti-Leu-13 and PGE2 on the CD3 pathway were additive and very inhibitory. The possibility that the Leu-13 signal reflects a mechanism by which a monocyte/macrophage-sensitive T cell activation pathway might be selectively amplified in vivo is discussed.

Antibodies, Monoclonal

Factors influencing the decision to rehabilitate: an initial comparison of rehabilitation candidates.

This study classified consecutive admissions to a U.S. Department of Veteran Affairs Medical Center. Patients on acute medical and surgical wards (n = 3170) were divided into clinical subgroups based on diagnostic, prognostic and functional criteria. The groups were: (1) independent; (2) terminal; (3) medical; (4) dementia; and (5) rehabilitation candidate. Medical record data from hospital admission, discharge and 9 month follow-up were collected. The groups had unique patterns of survival, residence and use of health care services during follow-up. Subsequently, rehabilitation participants were compared with a group similar in age, major diagnostic category and functional ability, who did not receive rehabilitation. Twenty-one percent of persons meeting study criteria for rehabilitation received rehabilitation services. At follow-up, participants in rehabilitation had lower mortality, spent less time in skilled care and were less frequently hospitalized. Although exploratory in nature, this study supports previously observed benefits of rehabilitation. In combination with clinical assessment, the process of identifying patient subgroups may be useful in planning interventions more uniformly and in developing measures to reduce selection bias in rehabilitation admission decisions.

Activities of Daily Living

Characteristics of hospital patients receiving medical rehabilitation: an exploratory outcome comparison.

This study classified consecutive hospital admissions to acute medical and surgical wards (n = 3,170) into clinical subgroups based on diagnostic, prognostic, and functional criteria. The groups were (1) independent, (2) terminal, (3) medical, (4) dementia, and (5) rehabilitation candidate. Medical record data from hospital admission, discharge, and nine-month follow-up were collected. The groups had unique patterns of survival, residence, and use of health care services during follow-up. Rehabilitation participants were compared with a group similar in age, major diagnostic category, and functional ability, who did not receive rehabilitation. Only 21% of persons meeting the study criteria for rehabilitation actually received rehabilitation services. At follow-up, participants in rehabilitation had lower mortality, spent less time in skilled nursing care, and were less frequently hospitalized. Although exploratory in nature, this study supports previously observed benefits of rehabilitation. In combination with clinical assessment, the process of identifying patient subgroups may be useful in planning interventions more uniformly and in developing measures to reduce selection bias in rehabilitation admission decisions.

Aged

Factors predicting satisfactory home care after stroke.

This study prospectively investigated factors predicting optimal poststroke home care. One hundred and thirty-five first occurrence stroke patients and their primary support persons were evaluated during the initial hospitalization after stroke and again one year poststroke. Discriminant function analysis was used to identify two groups from the baseline data: home care situations which were rated optimal and those which were not. Group membership was predicted and validated with 72.6% accuracy. Patients at risk for less than optimal home care had caregivers who were (1) more likely to be depressed, (2) less likely to be married to the patient, (3) below average in knowledge about stroke care, and (4) reporting more family dysfunction. Our findings suggest that caregiver-related problems can have a collective effect on rehabilitation outcome and that treatment should reduce caregiver depression, minimize family dysfunction, and increase the family's knowledge about stroke care.

Aged

Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells.

Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.

Antibodies, Monoclonal

The effect of age on digoxin pharmacokinetics in Fischer-344 rats.

Digoxin protein binding and pharmacokinetics were studied in 4-, 14-, and 25-month-old male Fischer-344 rats to determine if there were age-dependent changes in digoxin disposition. Serum protein binding did not differ among age groups. The average percentage unbound digoxin for all animals was 61.3 +/- 5.3% (means +/- SD, n = 15). For pharmacokinetic studies, [3H]digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group. The [3H]digoxin terminal elimination half-life was 2.0, 2.3, and 2.5 hr, respectively. The steady-state volume of distribution in the three age groups was 1.51, 1.49, and 1.27 liters/kg, respectively. Total body clearance for the three age groups was 14.2, 12.1, and 7.5 ml/min/kg, respectively. Analysis of variance of these data followed by Duncan's multiple range test indicated a significant decrease in clearance in the aged rats (25-month-old, p less than 0.05). This age-dependent decrease in clearance suggested that digoxin pharmacokinetics could be a significant factor in age-related alterations in digoxin cardiotoxicity in the rat, as it is in humans, and that the Fischer-344 rat could be a useful model for studies of digoxin pharmacokinetic changes with age.

Aging

Effects of prospective payment financing on rehabilitation outcome.

A suspected benefit of paying hospitals per diagnostic related groups (DRGs), i.e. the prospective payment system (PPS), is that lengths of stay (LOS) and costs may be reduced. A potential adverse effect is that providers may discharge patients to reduce costs regardless of clinical consequence. The Veterans Administration (VA) is one of the first agencies to adopt PPS for rehabilitation. This study analyzed the effects of PPS on LOS, readmission rate, nursing home placement (NHP), and referral for Home Health Care (HHC) on a 22 bed rehabilitation unit. One hundred and eighty-seven patients discharged in 1987, prior to the program, were compared (using t-tests) with 215 discharges in 1988, after PPS was established. There were no significant differences in demographics, self-care ability, or in readmissions. Referrals for HHC decreased significantly. LOS decreased from 29.3 days (SD = 16.4) in 1987 to 26.4 days (SD = 14.1) in 1988 (t = 5.3, p less than 0.01). However, 24 more patients were discharged to nursing homes in 1988 (N = 54, 25%) than in 1987 (N = 30, 16%), which represents an increase of 64% (p less than 0.05). Findings suggest that PPS may defer home care in favor of placement. Clinicians need to assess whether reducing inpatient LOS justifies increased use of nursing homes. Further research on the effects of PPS is needed to determine: (a) impact on clinical aspects of rehabilitation; and (b) if other funding mechanisms are more appropriate.

Diagnosis-Related Groups

Family satisfaction with medical care after traumatic brain injury.

Ratings during acute and follow-up care by 35 families having members with traumatic brain injury showed none of the medical facilities met families' needs though some aspects of patients' care were rated higher in hospitals. Findings suggest comprehensive surveys are needed.

Adolescent

Prospective payment for rehabilitation: effects on hospital readmission, home care, and placement.

Suspected benefits of a prospective payment system (PPS) in which hospitals are paid by diagnosis-related groups (DRGs) are that hospital lengths of stay and costs may be reduced. The US Department of Veterans Affairs is one of the first agencies to adopt PPS funding for rehabilitation; this early adoption of PPS provides a unique opportunity to test for both beneficial and adverse outcomes. This study compared hospital stay, readmission rate, and incidence of nursing home placement before and after introduction of PPS on a 22-bed rehabilitation service. Hospital stay decreased from 29.3 days to 26.4 days, but 64% more patients were discharged to nursing homes. Findings suggest that PPS may overlook home care in favor of placement, which neutralizes the cost benefits of the proposed reimbursement system. Further research on the effects of PPS is needed to determine (1) impact on clinical aspects of rehabilitation and (2) whether other funding mechanisms are more appropriate.

Diagnosis-Related Groups

Evaluation of the interaction of lithium and alprazolam.

A potential pharmacokinetic interaction between lithium and alprazolam was studied in 10 normal subjects. Pharmacokinetic parameters were determined from the following regimens: single-dose alprazolam, multiple-dose lithium, and multiple-dose alprazolam with lithium. Steady-state alprazolam clearance during multiple dosing with lithium was not different from that with the single dose of alprazolam. Lithium renal clearance decreased when it was coadministered with alprazolam (31.2 vs. 22.4 ml/minute, p less than 0.05). There was a small but significant increase in the steady-state area under the curve for lithium in the presence of alprazolam (10.3 vs. 11.1 mEq/hour/liter). The small increase in the serum lithium concentrations and decrease in lithium renal clearance was probably the result of lower urine flow rates (1.46 vs. 0.98 ml/minute, p less than 0.05) with the combination of the drugs. This is supported by a weak but significant linear relationship between urine flow rates and lithium renal clearance (N = 57, r = 0.353, p = 0.007). The percent of daily lithium dose recovered at steady-state from the 24-hour urine collection decreased significantly from 93.6% to 78.2% in the presence of alprazolam. This suggests that alprazolam may decrease lithium absorption. The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.

Adult

IFN-gamma and IFN-alpha induce the expression and synthesis of Leu 13 antigen by cultured human endothelial cells.

Leu 13 is a 16 kDa human lymphocyte surface Ag and monoclonal anti-Leu 13 induces T cell aggregation and alters T cell proliferation. In previous studies using anti-Leu 13, Leu 13 Ag has been detected on endothelial cells (EC) of arteries, capillaries, and veins in human tissue sections. In contrast, in this study using the same antibody, Leu 13 Ag could not be detected on unstimulated cultured human umbilical vein endothelial cells (HUVEC) by indirect immunofluorescence, immunoperoxidase staining, or immunoisolation of radiolabeled Ag from labeled endothelial cells. However, when HUVEC were cultured with IFN-gamma, Leu 13 Ag was demonstrable using all three detection techniques. Leu 13 Ag was detectable after 24 h of incubation with IFN-gamma (30 U/ml) and was maximally expressed after 72 h. After removal of IFN-gamma, Leu 13 Ag progressively declined back to basal levels by 4 days. Induction of Leu 13 Ag expression by IFN-gamma was suppressed by cycloheximide. Although Leu 13 Ag expression was also induced by IFN-alpha, PMA, and IL-1 were inactive. When HUVEC were incubated with IFN-gamma, surface-labeled with 125I, and then solubilized, anti-Leu 13 immunoisolated a 16-kDa radioactive band that comigrated with Leu 13 immunoisolated from T cells. Similar results were obtained using HUVEC that were metabolically labeled with 35S-methionine. These results demonstrate that HUVEC stimulated with IFN-gamma and IFN-alpha express Leu 13 Ag on their surface and suggest that exposure of EC to IFN may induce EC to develop new functional properties at sites of inflammatory and immune reactions.

Antibodies, Monoclonal

Timing of social work intervention and medical patient's length of hospital stay.

Findings report that hospital inpatients who receive social work intervention present difficult problems and have longer-than-average lengths of stay and that the earlier in the hospitalization that intervention occurs, the shorter the stay will be. A total of 243 patients referred for social services at a 440-bed teaching hospital were evaluated. Paired t-tests indicated a significant difference in the mean length of stay based on normative data. Timing of the intervention accounted for a significant amount of variance (13 percent) in length of hospital stay. The major clinical implications of the study are that social work intervention has the potential to decrease length of hospitalization, and that this methodology may be used reliably to evaluate changes in discharge planning protocol.

Adult