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Biomedical subjects

L W Moore

Publications and source records attributed to L W Moore.

At least 19 recordsLinked to original sources

Changes in abdominal wounds following treatment with sirolimus and steroids in a rat model.

Wound healing complications have been observed in patients receiving sirolimus (SLR). This study examined the degree and duration of delayed healing in various protocols using SLR. Sprague-Dawley rats underwent a standard midline abdominal incision and wound closure. Groups of 6 rats each were randomized to receive different doses of SLR (2 and 5 mg/kg) with or without loading dose (10 mg/kg x3 days), and with or without steroids (20 mg/kg x3 days followed by 5 mg/kg for 2 weeks). Rats were humanely killed on postoperative days 5, 10, or 15. Wound breaking force was measured using the EHMI BIAX-II instrument and tensile strength was calculated. Wounds in control animals had gradual increase in tensile strength during the 15-day observation. In contrast, high and loading doses of SLR caused reduction in wound strength until day 10, but the wounds' tensile strength became equivalent to control by day 15. The addition of steroids prolonged wound recovery with low doses of SLR until day 15 and had very profound effects on healing in high-dose SLR-treated animals (>50% reduction) that continued beyond the 2 weeks of observation. Low doses of SLR in non-steroid-treated animals had a short-term (5-day) impact on wound healing; high dose and loading doses delayed healing for 10 to 15 days. The addition of steroids had a synergistic effect on delayed wound healing, particularly in animals receiving high-dose SLR, which demonstrated prolonged wound weakness. These results may provide practical guidelines for postoperative introduction of SLR in the context of various clinical protocols.

Abdominal Injuries↗

Insights on the poster preparation and presentation process.

Dissemination of research findings and effective clinical innovations is key to the growth and development of the nursing profession. Several avenues exist for the dissemination of information. One forum for communication that has gained increased recognition over the past decade is the poster presentation. Poster presentations are often a significant part of regional, national, and international nursing conferences. Although posters are frequently used to disseminate information to the nursing community, little is reported about actual poster presenters' experiences with preparation and presentation of their posters. The purpose of this article is to present insights derived from information shared by poster presenters regarding the poster preparation and presentation process. Such insights derived from the personal experiences of poster presenters may assist others to efficiently and effectively prepare and present scholarly posters that disseminate information to the nursing community.

Attitude of Health Personnel↗

Older adults and HIV.

As the number of older Americans grows, perioperative nurses increasingly will be called on to provide services to older adults infected with HIV. To provide quality patient care, perioperative nurses must understand the facts about HIV and aging individuals. Finally, perioperative nurses must realize the best defense against exposure to bloodborne pathogens (e.g., HIV) is compliance with standard precautions while caring for all patients, from newborns to older adults.

Age Distribution↗

History of the professional councils of the National Kidney Foundation.

As the Councils move toward the new millennium, efforts to improve outcomes for patients with renal disease will be at the forefront. Each council has established a commitment to improving the quality of life for these individuals. Toward this goal, the CNNT, the CRN, and the CNSW will each propose programs to the NKF for improving the knowledge and skills of the professionals within these councils, promoting research within the respective scope of these professions, and working together to bring a better understanding of the issues confronted by the patients and the professionals as well. As an example of the combined effort of the Councils, the first joint project of the century will be to bring the communications packages of each council under a common framework by joining the newsletters of each council. It is an exciting time to be part of the NKF. As a professional in the renal community, being a part of the CNNT, the CRN, or the CNSW offers a professional enrichment and opportunities to participate in making lives better for those with renal disease.

Administrative Personnel↗

Severe visual impairment in older women.

The purpose of this qualitative, phenomenological study was to uncover the meaning of severe visual impairment to older women diagnosed with macular degeneration, a leading cause of blindness in older adults. The research question for the study was, What is the lived experience of severe visual impairment in older women diagnosed with macular degeneration? Participants were eight women, aged 63 to 85 years, who had been diagnosed with macular degeneration and who had severe visual deficits. Data were gathered through audiotaped interviews. Interview recordings were transcribed and later analyzed using a modified Giorgi methodology. The meaning of severe visual impairment emerged as "persisting toward unfolding ways of being in the world sparked by personal discoveries amidst enveloping losses while embracing a realistic awareness with steadfast positivism." Findings from this study were congruent with the theory of Human Becoming. Study findings highlight factors that may place older women with severe visual deficits at risk for lower levels of well-being.

Activities of Daily Living↗

The US multicenter double-blind, randomized, phase III trial of thymoglobulin versus atgam in the treatment of acute graft rejection episodes following renal transplantation: rationale for study design.

In this study intended to establish equivalence between two antibody therapies for acute rejection in kidney transplant recipients, it was important to develop a rigorous protocol. Assurance of the presence of acute rejection was imperative. Therefore, due to the lack of literature support for clinical assessment of renal dysfunction, histologic diagnosis of acute rejection was required for enrollment in the study. Likewise, supportive literature for a correlation between response to anti-rejection therapy and the severity of rejection lead to the decision that the study should be stratified by a measurement of rejection severity for which Banff criteria were used. Finally, quantification of the response to therapy was also measured against the available literature and a large, newly developed international database of kidney transplant rejection episodes (the Efficacy Endpoints database) where serum creatinine, expressed as a percentage of the baseline level at the time of rejection was shown to be the most effective, available clinical marker of rejection response. Therefore, the US Multicenter Phase III Trial for comparing Thymoglobulin to Atgam in the treatment of acute rejection exhibits a unique and detailed study design that could be implemented in future trials as well as in clinical practice to improve assessment of outcomes.

Antilymphocyte Serum↗

Initiating research with doubly vulnerable populations.

Some research questions can only be answered by members of a vulnerable group. Frequently members of these groups are doubly vulnerable as they experience more than one factor that diminishes their autonomy. Initiating research with doubly vulnerable persons presents unique and often difficult challenges. Because of these challenges, many researchers purposefully exclude doubly vulnerable groups from research endeavours. Thus, the health care needs and concerns of individuals considered doubly vulnerable are often not addressed in the scientific literature. This article presents two challenges frequently encountered when initiating research with doubly vulnerable populations: resolving pre-investigation issues and gaining access to vulnerable populations. Ethically sound strategies for confronting these challenges are discussed. Researchers' experiences with doubly vulnerable populations are also incorporated. Only when doubly vulnerable groups receive the appropriate research attention are the standards of their care and their quality of life enhanced.

Ethics, Nursing↗

Correlation of histology to clinical rejection reversal: a thymoglobulin multicenter trial report.

UNLABELLED: Correlation of histology to rejection reversal: A Thymoglobulin Multicenter Trial report BACKGROUND: Histology may provide a link between clinical response to antirejection therapy and graft function. In a subset of centers, renal biopsy was a secondary end point for the Thymoglobulin Multicenter Trial. METHODS: Thirty-eight patients had a protocol biopsy one to two weeks following the end of therapy. Inclusion and post-treatment biopsies were graded and scored according to Banff criteria by a central pathologist who was blinded to the type and outcome of therapy and the timing of the biopsy. RESULTS: The majority of patients (31 of 38) had moderate rejection on their inclusion biopsy. An improvement of at least one Banff grade occurred in 58% of the patients. The treatment was clinically successful in 33 patients, but two thirds of the patients (25 out of 38) demonstrated residual inflammation in the graft. The degree of improvement of inflammation was proportionate to rejection severity (P = 0.006). Banff scoring indicated that residual inflammation was less in Thymoglobulin-treated patients than in those receiving Atgam (P < 0.05) and correlated with the incidence of recurrent rejection (P = 0.015). CONCLUSIONS: These data demonstrate a discrepancy between clinical and histological resolution of acute renal allograft rejection. Residual infiltrates in the graft following rejection therapy are common and, despite clinical improvement, may indicate an increased risk for recurrent rejection.

Acute Disease↗

Utility of standardized histological classification in the management of acute rejection. 1995 Efficacy Endpoints Conference.

BACKGROUND: Standardized histological grading of transplant kidney biopsies has become a primary criterion for diagnosis of rejection in immunosuppression clinical trials. METHODS: A consortium of 19 transplant centers from North America, Europe, and Australia convened in 1995 to examine kidney transplant rejection. Data from the 1995 Efficacy Endpoints Conference were examined for frequency of adoption of Banff schema. Biopsy grading was correlated with clinical parameters of rejection and therapy response. RESULTS: Histological confirmation of rejection episodes occurred in 73% of 953 cases, with Banff criteria adoption increasing in frequency between 1992 and 1995. Banff grading significantly correlated with clinical rejection severity (rejection creatinine: grade I, 2.8+/-0.2 mg/dl; grade II, 3.5+/-0.2 mg/dl; grade III, 4.1+/-0.3 mg/dl; P < 0.001), although nadir creatinines were similar. Response rates of Banff grades I and II to steroid therapy were not different, but only 42% of grade III rejections responded to steroids (P < 0.003. Banff grading also correlated with postrejection creatinine, day 15: grade I, 2.2+/-0.2 mg/dl; grade II, 3.0+/-0.2 mg/dl; grade III, 3.8+/-0.4 mg/dl (P < 0.001), and day 30: grade I, 2.1+/-0.1 mg/dl; grade II, 2.2+/-0.2 mg/dl; grade III, 2.7+/-0.2 mg/dl (P < 0.06). Banff grade III correlated with reduced graft survival at 1 year: grade I, 86%; grade II, 88%; grade III, 70% (P < 0.01). CONCLUSIONS: This multicenter review of rejection severity confirms that standardized histologic classifications such as the Banff schema provide a reliable means for stratifying patient risk of treatment success or failure. These data support the use of Banff criteria in clinical trial design.

Acute Disease↗

Efficacy Endpoints Conference on Acute Rejection in Kidney Transplantation: summary report of the database.

An international database of rejection episodes and their characteristics with regard to definition and follow-up parameters was developed to improve the approach to protocol development for clinical trials. Nineteen North American, European, and Australian centers uniformly reported on 50 consecutive transplant rejection episodes. Data collected included patient demographic parameters, induction and maintenance immunosuppression therapies, rejection agents (drug, dose, duration), clinical signs (50% decrease in urine, fever), serum creatinine (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), histopathological findings, morbidity, recurrence of rejection, and function at 1 year. The centers contributed a total of 953 presumed rejection episodes, of which 842 were confirmed as acute rejection episodes. The majority of cases were first rejections (81%), and rejection occurred 119 +/- 345 days following transplantation. The Banff Schema of histological grading was used in 38% of biopsy-proven rejection episodes (2% Borderline, 42% Grade I, 38% Grade II, 18% Grade III). Only 30% of all rejections showed clinical signs that were most likely to occur in Grade III rejection episodes (P < 0.006). The serum creatinine response was well below the rejection creatinine level by day 15 following initiation of antirejection therapy in the majority of cases. A significant number of the cases (34%) reported in this database experienced a recurrent rejection approximately 85 days following the first rejection. Graft survival 1 year following the rejection episode was good (83%). These findings will facilitate development of clinical trial design and beneficially impact approaches to antirejection therapies for kidney allograft recipients.

Acute Disease↗

Proposed consensus for definitions and endpoints for clinical trials of acute kidney transplant rejection.

Progress in transplantation therapeutics requires validation from multicenter trials in which enrollment criteria and endpoint definitions have been standardized. A database of acute rejection was established from 19 North American, European, and Australian transplant centers and included parameters on rejection diagnosis and treatment of 50 consecutive rejection episodes from each center. Patient demographics, induction and maintenance immunosuppressive therapies, antirejection agents (drug, dose, duration), clinical signs (decrease in urine volume, presence of fever of > or =38.5 degrees C), serum creatinine concentration (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), rejection biopsy findings, morbidity, recurrence of rejection, and renal function at 1 year were recorded for 953 rejection episodes. From these data, three definitions were proposed. Acute rejection was defined as an immunologic process resulting in a serum creatinine increase of > or =0.4 mg/dL, with or without clinical signs, and should include a biopsy confirmation that has been standardized to the Banff criteria. Corticosteroid-resistant rejection was defined as a rejection episode in which a minimum of 250 to 1000 mg of methylprednisolone administered as initial therapy fails to result in stabilization or reduction of the serum creatinine after 3 days of corticosteroid treatment. Successful response to therapy was defined as a serum creatinine level < or =110% of the serum creatinine on the day of the rejection diagnosis and a return of the serum creatinine to or below the rejection creatinine level by 5 days of therapy with maintenance of this response for a minimum of 30 days. The work represented in the Efficacy Endpoints Database provides a step toward improving definitions in clinical trials. Continuity in clinical trial design should lead to improvements in evaluation of outcomes and, thereby have an effect on clinical practice.

Acute Disease↗

Observations on recovery of renal function following treatment for acute rejection.

The characteristics of rejection and rejection response have not been systematically described in renal transplant recipients. The Efficacy Endpoints Conference Database contains characteristics from 953 episodes of rejection occurring at 19 North American, European, and Australian transplant centers. This database was used to profile renal transplant rejection episodes treated with primary steroid therapy, primary antilymphocyte antibody therapy, and rescue antilymphocyte antibody therapy. Primary steroid therapy was used in 88% of the rejection episodes. A successful response was more common in recipients without fever (72% v 61%; P < 0.004), in recipients experiencing less than a Banff Grade III rejection (92% v 75%; P = 0.009), and was more likely associated with graft function at 1 year following the rejection than rejection episodes that failed steroid therapy (89% v 82%; P = 0.013). Steroid success was statistically identifiable by day 2 of therapy and clinically useful by day 3; serum creatinine on these days of therapy is shown as a ratio of the rejection creatinine (102% v 112% day 1, success v failure, P< 0.002; 104% v122% day 2, success v failure, P < 0.0001; 105% v125% day 3, success vfailure, P < 0.0001). Response to primary antilymphocyte antibody therapy reached significance at day 5 of therapy when serum creatinine decreased below the rejection creatinine level in antilymphocyte successes but remained at or above the rejection creatinine in those who failed the therapy (90% v 135%; P < 0.01). For rescue antilymphocyte antibody therapy, a response was evident after 5 days of therapy (approximately day 9 to 10 of rejection) when serum creatinine began to decline and continued lower throughout the 10-day course of antilymphocyte antibody therapy (day 14 to 15 of rejection; serum creatinine 3.0 mg/dL v 4.4 mg/dL for success v failure; P < 0.004). Serum creatinine was lower throughout the first year following therapy in each success group (steroids, antilymphocyte antibody therapy as primary or as rescue), and a greater percentage of failures of any of the three therapies resulted in graft loss. Interestingly, 1-year graft survival was not different in the patients who were treated with antilymphocyte antibody therapy as primary than those who received these antirejection agents as rescue therapy (81% and 84%, respectively). The Efficacy Endpoints Conference Database provides an essential tool for profiling acute rejection in renal transplantation and should lead to improved evaluation of rejection therapies.

Acute Disease↗

Comparison of two cyclosporine formulations in healthy volunteers: bioequivalence of the new Sang-35 formulation and Neoral.

This study was conducted to establish bioequivalence between a newly developed oral cyclosporine formulation, Sang-35 (SangStat Medical Corp., Menlo Park, CA), and the microemulsion formulation Neoral (Novartis Pharmaceuticals, East Hanover, NJ). In a randomized, open-label, two-way crossover study, 36 fasted, healthy male volunteers received a single 500-mg cyclosporine dose formulated either as Sang-35 or Neoral. Mean are under the concentration-time curve to infinity (AUC0-infinity) for Sang-35 was 13,900 microg x hr/L compared with 14,000 microg x hr/L for Neoral, with a 90% confidence interval (CI) of 96% to 103% for the geometric mean ratio of the two formulations. Mean maximum concentration (Cmax) was 1,690 microg/L for Sang-35 and 1,700 microg/L for Neoral, with a 90% CI of 96% to 103%. Geometric mean ratios for both AUC0-infinity and Cmax were within the acceptance criteria for bioequivalence (80-125%). Additional studies showed no differences between Sang-35 and Neoral after high-fat meals (n = 19), in female volunteers (n = 25) and in black volunteers (n = 7). It is concluded that single doses of the oral cyclosporine formulations Sang-35 and Neoral are bioequivalent in healthy fasted subjects, after high-fat meals, in women, and in blacks.

Administration, Oral↗

Diversity of opines and opine-catabolizing bacteria isolated from naturally occurring crown gall tumors.

The diversity of opines from 43 naturally occurring crown gall tumors on several plant species was analyzed for the presence of agropine, chrysopine, iminodiacid, an unidentified leucinopine-like iminodiacid (IDA-B), mannopine, octopine, nopaline, DL- and LL-succinamopine, leucinopine and heliopine. Opine utilization patterns of agrobacteria and fluorescent pseudomonads resident in a tumor were then analyzed and compared for agreement with the opine isolated from that tumor. Nopaline was the most common opine found and was detected in tumors from cherry, blackberry, grape, and plum. Octopine was not found, although octopine-catabolizing bacteria were isolated from several tumors. A new, previously undescribed iminodiacid of the succinamopine-leucinopine type (provisionally designated IDA-B) was isolated from tumors of wild blackberry. Field tumors from apple, blueberry and grape yielded no detectable opines, even though opine-utilizing bacteria were present. Bacterial isolates from plum and cherry showed the best correspondence between the opine in tumors (nopaline) and the presence of bacteria that catabolized that opine. However, several unusual opine catabolic combinations were identified, including isolates that catabolized a variety of opines but were nonpathogenic. More variability was observed among isolates from field tumors on the remaining plant species. We isolated novel mannopine-nopaline type agrobacteria from field tumors of cherry, plum and blackberry that induced tumors containing either mannopine (plus agropine) or nopaline, but not both. Epidemiologically, the galled plants from an area were not of clonal origin (same Ti plasmid), indicating that the field tumors from a small area were incited by more than one type of Ti plasmid.

Journal Article↗

The correlation of Banff scoring with reversibility of first and recurrent rejection episodes.

Recurrent acute rejection remains a significant problem for recipients of renal allografts, with a large proportion of patients progressing to graft loss. The newly introduced Banff schema was used to determine whether the histologic pattern of acute rejection (severity and renal compartment scoring) could discriminate recurring from nonrecurring rejections and to examine whether objective rejection scoring had predictive value for rejection reversal and outcome. A total of 67 biopsies obtained from 50 patients with acute rejection were examined for the occurrence of recurrent allograft rejection. All patients were maintained on a cyclosporine-based triple immunosuppressive protocol and had biopsy-proven acute rejection without chronic changes. Rejection recurred in 13 patients (26%), of whom 4 further developed a third rejection. The majority of the patients developed this first rejection within 2 months posttransplantation. Demographics, prebiopsy renal function, immunosuppression, and peak serum creatinine level at the time of biopsy were similar in patients with multiple and single rejection. Peak levels of reactivity to panel of lymphocytes seemed higher in the group of patients with recurrent rejection, whereas HLA matching was similar for all patients. Banff scores for acute rejection did not discriminate patients at risk of rejection recurrence who had lower vascular (0.6 vs. 1.2), tubular (0.6 vs. 1.1), and lower cumulative SUM (3.0 vs. 4.5) scores on their first rejection when compared with patients with one rejection. Histological scoring was, however, significantly different when first and third episodes were compared in the same patient, indicating increased rejection severity with recurrence. Moreover, the rate of reversal of recurrent rejection by anti-lymphocyte therapy was significantly less than that of first rejection (P<0.05). In conclusion, these data demonstrate that Banff scoring correlated with rejection reversal and steroid responsiveness, yet rejection recurrence was independent of histological score of the first rejection. Furthermore, Banff schema provided an objective histological correlation to the poor clinical outcome seen with recurrent rejection. The data also suggest that patients with early mild rejection continue to be at risk for recurrence and graft loss.

Acute Disease↗

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole.

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoconazole group versus the no ketoconazole group, respectively, P<0.05). Weight gain changes were different between the ketoconazole group and no ketoconazole group (6.4 +/- 1.4 kg versus 5.0 +/- 1.3 kg) at six months and an increased rate of weight gain over time in the ketoconazole group (0.02 kg/day at one month versus 0.05 kg/day at six months, P<0.007). Effectiveness of ketoconazole inhibition of cyclosporine is valuable, but inhibition of other metabolic pathways should be evaluated as well.

Adolescent↗