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Biomedical subjects

J L Payne

Publications and source records attributed to J L Payne.

17 recordsLinked to original sources
PubMed2001

FES-Cre targets phosphatidylinositol glycan class A (PIGA) inactivation to hematopoietic stem cells in the bone marrow.

A somatic mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene causes the loss of glycosyl phosphatidylinositol (GPI)-linked proteins on blood cells from patients with paroxysmal nocturnal hemoglobinuria. Because all blood cell lineages may be affected it is thought that the mutation occurs in a hematopoietic stem cell. In transgenic mice, germline transmission of an inactive Piga gene is embryonic lethal. To inactivate the murine Piga gene in early hematopoiesis we therefore chose conditional gene inactivation using the Cre/loxP system. We expressed Cre recombinase under the transcription regulatory sequences of the human c-fes gene. FES-Cre inactivated PIGA in hematopoietic cells of mice carrying a floxed Piga allele (LF mice). PIGA(-) cells were found in all hematopoietic lineages of definitive but not primitive hematopoiesis. Their proportions were low in newborn mice but subsequently increased continuously to produce for the first time mice that have almost exclusively PIGA(-) blood cells. The loss of GPI-linked proteins occurred mainly in c-kit(+)CD34(+)Lin(-) progenitor cells before the CFU-GEMM stage. Using bone marrow reconstitution experiments with purified PIGA(-) cells we demonstrate that LF mice have long-term bone marrow repopulating cells that lack GPI-linked proteins, indicating that recombination of the floxed Piga allele occurs in the hematopoietic stem cell.

Animals↗
PubMed2000

Health-related quality of life after different types of solid organ transplantation.

OBJECTIVE: To describe functional health and health-related quality of life (QOL) before and after transplantation; to compare and contrast outcomes among liver, heart, lung, and kidney transplant patients, and compare these outcomes with selected norms; and to explore whether physiologic performance, demographics, and other clinical variables are predictors of posttransplantation overall subjective QOL. SUMMARY BACKGROUND DATA: There is increasing demand for outcomes analysis, including health-related QOL, after medical and surgical interventions. Because of the high cost, interest in transplantation outcomes is particularly intense. With technical surgical experience and improved immunosuppression, survival after solid organ transplantation has matured to acceptable levels. More sensitive measures of outcomes are necessary to evaluate further developments in clinical transplantation, including data on objective functional outcome and subjective QOL. METHODS: The Karnofsky Performance Status was assessed objectively for patients before transplantation and up to 4 years after transplantation, and scores were compared by repeated measures analysis of variance. Subjective evaluation of QOL over time was obtained using the Short Form-36 (SF-36) and the Psychosocial Adjustment to Illness Scale (PAIS). These data were analyzed using multivariate and univariate analysis of variance. A summary model of health-related QOL was tested by path analysis. RESULTS: Tools were administered to 100 liver, 94 heart, 112 kidney, and 65 lung transplant patients. Mean age at transplantation was 48 years; 36% of recipients were female. The Karnofsky Performance Status before transplantation was 37 +/- 1 for lung, 38 +/- 2 for heart, 53 +/- 3 for liver, and 75 +/- 1 for kidney recipients. After transplantation, the scores improved to 67 +/- 1 at 3 months, 77 +/- 1 at 6 months, 82 +/- 1 at 12 months, 86 +/- 1 at 24 months, 84 +/- 2 at 36 months, and 83 +/- 3 at 48 months. When patients were stratified by initial performance score as disabled or able, both groups merged in terms of performance by 6 months after liver and heart transplantation; kidney transplant patients maintained their stratification 2 years after transplantation. The SF-36 physical and mental component scales improved after transplantation. The PAIS score improved globally. Path analysis demonstrated a direct effect on the posttransplant Karnofsky score by time after transplantation and diabetes, with trends evident for education and preoperative serum creatinine level. Although neither time after transplantation nor diabetes was directly predictive of a composite QOL score that incorporated all 15 subjective domains, recent Karnofsky score and education level were directly predictive of the QOL composite score. CONCLUSIONS: Different types of transplant patients have a different health-related QOL before transplantation. Performance improved after transplantation for all four types of transplants, but the trajectories were not the same. Subjective QOL measured by the SF-36 and the PAIS also improved after transplantation. Path analysis shows the important predictors of health-related QOL. These data provide clearly defined and widely useful QOL outcome benchmarks for different types of solid organ transplants.

Critical Pathways↗
PubMed1998

Experience with neoral versus sandimmune in primary liver transplant recipients.

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 +/- 1.9 days in the Neoral group vs 7.8 +/- 4.9 days in the Sandimmune group. (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13%) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year post-transplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70% using Sandimmune.

Adult↗
PubMed1998

Outcomes analysis in 100 liver transplantation patients.

BACKGROUND: There is an increasing demand for outcomes analysis, including quality of life and financial analysis, following medical interventions and surgical procedures. We analyzed outcomes for 100 consecutive patients undergoing liver transplantation during a period of case management revision. METHODS: Patient survival was calculated by Kaplan-Meier actuarial methods. The Karnofsky performance status was objectively assessed for surviving patients up to 6 years after transplantation and was evaluated by repeated measures analysis of variance and covariance. Subjective evaluation of quality of life over time was obtained using the Psychosocial Adjustment to Illness Scale. The correlations between time and scale were calculated. Financial data were accumulated from billing records. RESULTS: Six-month, 1-year, 2-year, and 3- through 5-year survival was 86%, 84%, 83%, and 78%, respectively. Karnofsky performance status confirmed poor functional status preoperatively with a mean of 53 +/- 2, but significantly improving to 72 +/- 2 at 3 months, 80 +/- 2 at 6 months, 90 +/- 1 at 1 year, 92 +/- 1 at 2 years, 94 +/- 1 at 3 years, 96 +/- 1 at 4 years, and 97 +/- 1 at 5 years (P <0.001). Psychosocial Adjustment to Illness Scale scores demonstrated significant improvement following transplantation overall (r = -0.33), improving most in sexual relationships (r = -0.41), and domestic environment (r = -0.35; P <0.001). Median length of stay for the first half of the patients was 19 days declining to 11 days for the second half. Median hospital charges declined from $105,000 to $90,000. CONCLUSIONS: Quality of life parameters assessed both by care givers (Karnofsky) and by patients (Psychosocial Adjustment to Illness Scale) improved dramatically following transplantation and over time, demonstrating that liver transplantation effectively restores a good quality of life. Outcomes can be improved while reducing length of stay and charges through modifications in case management.

Adaptation, Psychological↗
PubMed1998

Relationship of cognitive and functional impairment to depressive features in Alzheimer's disease and other dementias.

Patients with clinical diagnoses of Alzheimer's disease, vascular dementia, or undifferentiated dementia were rated on standardized measures of depression, cognitive impairment, and functional impairment. Logistic regression was used to evaluate the relationship between functional or cognitive impairment, as well as their interaction, and depressive features in each group. This analysis revealed notable differences by type of dementia. The results imply that the mechanisms underlying depression in Alzheimer's disease may be different from those in vascular and other types of dementia. These results also provide indicators to the clinician for further evaluation of depression in different dementia subtypes.

Aged↗
PubMed1996

Leukocyte lipid body formation and eicosanoid generation: cyclooxygenase-independent inhibition by aspirin.

Lipid bodies, cytoplasmic inclusions that develop in cells associated with inflammation, are inducible structures that might participate in generating inflammatory eicosanoids. Cis-unsaturated fatty acids (arachidonic and oleic acids) rapidly induced lipid body formation in leukocytes, and this lipid body induction was inhibited by aspirin and nonsteroidal antiinflammatory drugs (NSAIDs). Several findings indicates that the inhibitory effect of aspirin and NSAIDs on lipid body formation was independent of cyclooxygenase (COX) inhibition. First, the non-COX inhibitor, sodium salicylate, was as potent as aspirin in inhibiting lipid body formation elicited by cis-fatty acids. Second, cis-fatty acid-induced lipid body formation was not impaired in macrophages from COX-1 or COX-2 genetically deficient mice. Finally, NSAIDs inhibited arachidonic acid-induced lipid body formation likewise in macrophages from wild-type and COX-1- and COX-2-deficient mice. An enhanced capacity to generate eicosanoids developed after 1 hr concordantly with cis-fatty acid-induced lipid body formation. Arachidonic and oleic acid-induced lipid body numbers correlated with the enhanced levels of leukotrienes B4 and C4 and prostaglandin E2 produced after submaximal calcium ionophore stimulation. Aspirin and NSAIDs inhibited both induced lipid body formation and the enhanced capacity for forming leukotrienes as well as prostaglandins. Our studies indicate that lipid body formation is an inducible early response in leukocytes that correlates with enhanced eicosanoid synthesis. Aspirin and NSAIDs, independent of COX inhibition, inhibit cis-fatty acid-induced lipid body formation in leukocytes and in concert inhibit the enhanced synthesis of leukotrienes and prostaglandins.

Adult↗
PubMed1996

Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids.

Lipid bodies, lipid rich cytoplasmic inclusions, are characteristically abundant in vivo in leukocytes associated with inflammation. Because lipid bodies are potential reservoirs of esterified arachidonate and sites at which eicosanoid-forming enzymes may localize, we evaluated mechanisms of lipid body formation in neutrophils (PMN). Among receptor-mediated agonists, platelet activating factor (PAF), but not C5a, formyl-methyl-phenylalanine, interleukin 8, or leukotriene (LT) B4, induced the rapid formation of lipid bodies in PMN. This action of PAF was receptor mediated, as it was dose dependently inhibited by the PAF receptor antagonist WEB 2086 and blocked by pertussis toxin. Lipid body induction by PAF required 5-lipoxygenase (LO) activity and was inhibited by the 5-lipoxygenase-activating protein antagonist MK 886 and the 5-LO inhibitor zileuton, but not by cyclooxygenase inhibitors. Corroborating the dependency of PAF-induced lipid body formation on 5-LO, PMN and macrophages from wild-type mice, but not from 5-LO genetically deficient mice, formed lipid bodies on exposure to PAF both in vitro and in vivo within the pleural cavity. The 5-LO product inducing lipid body formation was not LTB4 but was 5(S)-hydroxyeicosatetraenoic acid [5(S)-HETE], which was active at 10-fold lower concentrations than PAF and was also inhibited by pertussis toxin but not by zileuton or WEB 2086. Furthermore, 5-HETE was equally effective in inducing lipid body formation in both wild-type and 5-LO genetically deficient mice. Both PAF- and 5(S)-HETE-induced lipid body formation were inhibited by protein kinase C (PKC) inhibitors staurosporine and chelerythrine, the phospholipase C (PLC) inhibitors D609 and U-73122, and by actinomycin D and cycloheximide. Prior stimulation of human PMN with PAF to form lipid bodies enhanced eicosanoid production in response to submaximal stimulation with the calcium ionophore A23187; and the levels of both prostaglandin (PG) E2 and LTB4 correlated with the number of lipid bodies. Furthermore, pretreatment of cells with actinomycin D or cycloheximide inhibited not only the induction of lipid body formation by PAF, but also the PAF-induced "priming" for enhanced PGE2 and LTB4 in PMN. Thus, the compartmentalization of lipids to form lipid bodies in PMN is dependent on specific cellular responses that can be PAF receptor mediated, involves signaling through 5-LO to form 5-HETE and then through PKC and PLC, and requires new protein synthesis. Since increases in lipid body numbers correlated with priming for enhanced PGE2 and LTB4 production in PMN, the induction of lipid bodies may have a role in the formation of eicosanoid mediators by leukocytes involved in inflammation.

Animals↗
PubMed1996

Soluble beta-amyloid induces Alzheimer's disease features in human fibroblasts and in neuronal tissues.

It has been shown that K+ channels, Cp20 (a 20kD GTP-binding protein), and intracellular calcium release, play a key role in associative memory storage. These same elements have been shown to be altered in fibroblasts from Alzheimer's Disease (AD) patients. In addition, it has been shown that PKC, also implicated in memory storage and closely related to the above mentioned components, is also altered in AD fibroblasts. Moreover, beta-amyloid was capable of inducing an AD-like phenotype for K+ channels and Cp20 in otherwise normal fibroblasts, providing additional evidence for the potential involvement of these components in AD and suggesting a possible pathological consequence of soluble beta-amyloid elevation in AD. Preliminary evidence shows that comparable changes in potassium channel function are also present in human olfactory neuroblasts from AD patients. These results indicate that the observed changes not only occur in peripheral tissues such as fibroblasts, but also in neural tissue, the primary site of AD pathology.

Alzheimer Disease↗
PubMed1996

CNS role evolution.

THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.

Curriculum↗
PubMed1996

Outcomes analysis for 50 liver transplant recipients: the Vanderbilt experience.

Healthcare reform has mandated scrutiny of the fiscal aspects of patient care as well as medical outcomes. Therefore, we reviewed our experience with 50 liver transplant recipients from a multidisciplinary collaborative transplant team. From February 1991 to July 1994, of 175 patients referred, 75 were formally evaluated for transplantation; 56 (76%) of these patients were accepted for transplantation; 50 patients underwent 53 transplants. Operative mortality of 6 per cent, retransplantation rate of 6 per cent, 6-month actuarial survival of 88 per cent, 1-year survival of 86 per cent, and the 2 and 3-year survival of 83 per cent were unchanged over time. Quality of life evaluated by the Karnofsky Performance Status was a mean of 55 pretransplant, 72 at 3 months, 79 at 6 months, 84 at 1 year, 88 at 2 years, and 95 at 3 years, demonstrating improved general health and functional rehabilitation after transplantation. Psychosocial Adjustment to Illness Scale scores demonstrated significant improvement following transplantation, improving most dramatically in the vocation environment, domestic environment, and sexual relationship domains. Postoperative length of stay has declined with an average of 28 days in 1991, 22 days in 1992, 19 days in 1993, and 14 days in 1994. Average total hospital, organ procurement, and physician charges for the transplantation hospitalization was $165,000. Average 91-92 hospital charges were $154,000 and were reduced in 93-95 to $103,000 (P < .05). We found that charges and length of stay decreased over time, while the outcome and quality of patient care was maintained. We believe the collaborative practice, case management, and revised patient care protocols are responsible.

Activities of Daily Living↗
PubMed1992

Immune modification and complications of immunosuppression.

For transplant recipients, immunosuppression is necessary to prevent rejection. The type of immunosuppression varies according to the patient and institution; however, most patients receive double or triple drug regimens. Thus, thorough nursing assessment and intervention are essential throughout the transplant period. Research in this area continues, leading to a promising future for transplantation.

Humans↗
PubMed1986

Increasing the graduation rates of minority medical students.

The University of Illinois College of Medicine has operated a program since 1969 to recruit minority students into the college and to increase the graduation rates of these students once they enroll. Known as the Medical Opportunities Program (MOP) until 1978, the program was expanded in 1978 and renamed the Urban Health Program (UHP). The authors of the present paper discuss the results of these programs, particularly the effect of granting minority students delays in completing graduation requirements. The MOP (1969 through 1978) increased graduation rates for minority students from 55 percent for those who graduated on time to 81 percent for both on-time and delayed graduates. Under the first seven years of the UHP (1979 through 1985), more minority students have been offered places, and more have enrolled than in the 10 years of the MOP. The retention rate under the UHP, if it holds, will be higher than that under the MOP. For the combined MOP-UHP period, the retention rate for minority students was 88 percent; 69.8 percent of the graduates were on time, and 30.2 were delayed.

Curriculum↗
PubMedDate not supplied

Treadmill exercise during adenosine infusion is safe, results in fewer adverse reactions, and improves myocardial perfusion image quality.

BACKGROUND: Combining low-level treadmill exercise with adenosine infusion may result in fewer bradyarrhythmic complications by increasing sympathetic tone and may improve myocardial perfusion image quality by decreasing background activity. METHODS: Patients referred for outpatient pharmacologic stress myocardial perfusion imaging performed simultaneous treadmill exercise (mean 2.2 metabolic equivalents) throughout 6-minute adenosine infusion (adenosine-exercise n = 507). Patients unable to exercise and those with left bundle branch block received adenosine infusion alone (adenosine-nonexercise n = 286). Adverse reaction data were collected on all patients and compared by sex. Background-to-target activity was calculated in a blinded fashion on 200 randomly selected patients. RESULTS: During the period from April 1996 to December 1998, 507 patients (64%) underwent adenosine-exercise testing, whereas 286 (36%) underwent adenosine-nonexercise testing. Hypotensive and arrhythmic (atrioventricular block, sinus bradycardia, and new onset atrial fibrillation or flutter) adverse reactions occurred less often during adenosine-exercise than during adenosine-nonexercise. Neither death nor myocardial infarction occurred in either group. In the adenosine-exercise group, 2.8% of patients experienced an adverse reaction versus 5.6% of the adenosine-nonexercise group (P = .04). The reduction in adverse reactions occurred in both men and women, although women had significantly more adverse reactions than men (5.7% vs 1.8%, P = .004). Liver/heart and gut/heart ratios were lower in the adenosine-exercise group (1.05+/-0.42 vs. 1.21+/-0.55 , P = .01; 0.61+/-0.21 vs. 0.69+/-0.24, P = .03, respectively). CONCLUSIONS: Compared with adenosine infusion alone, combining low-level treadmill exercise with adenosine in outpatients is safe, better tolerated, and improves image quality. Women were more likely to experience adverse reactions than men.

Adenosine↗
PubMedDate not supplied

The impact of a College of Nursing Retention Program on the graduation rates of nursing students.

This study was designed to measure the impact of a College of Nursing's (CON) Retention Program on students enrolled in a baccalaureate degree nursing program. Within the last ten years, undergraduate nurses increasingly have utilized the CON retention program. These students traditionally face a number of barriers to their academic endeavors. This study was designed to assess the effect of the CON program on the barriers to academic success of students who entered the CON in the Fall classes of 1991, 1992 and 1993. The sample size was 320 students. The control group consisted of 137 students who received no intervention and the experimental group was comprised of 183 students who attended intervention sessions with the Retention Coordinator in the CON. It was hypothesized that the most successful students during this period (1991-1993) were the most frequent attendees of the CON retention program intervention sessions. The alternative hypothesis was that those persons who did not attend the sessions, but were still highly persistent and successful, were enrollees who had entered with high entrance credentials as demonstrated by the transfer grade point averages (GPA). The results of this study indicated the need, use and value of this systematic approach to retention.

Adaptation, Psychological↗
PubMedDate not supplied

Subject acceptance of implanted auditory prosthesis.

Each of the 13 subjects was interviewed, in a structured context, to determine their estimate of the value of the prosthesis to their daily life. The subjects who used their prostheses eight or more hours a day reported it to be more valuable in their daily living than did those who used it less than eight hours a day. The fulltime users reported that the prosthesis is most helpful to them as an adjunct to lipreading. All of them thought the prosthesis valuable in terms of "hearing" environmental sounds. While all of them reported noisy environments to be bothersome, the fulltime users did not turn off their stimulators in noise. Only two subjects, both infrequent users of their prostheses, reported that they would not undergo implant surgery again.

Cochlea↗