Intragraft mRNA cytotoxic molecule expression in renal allograft recipients.

The gene expression of the cytotoxic T-cell molecules perforin, granzyme B and Fas ligand are associated with acute rejection in renal allograft recipients. Several immune mechanisms are linked to severe systemic inflammation in brain-dead organ donors. We examined the mRNA expression of these T-cell activation biomarkers in donor kidney biopsies to evaluate if they could separate living from deceased donors and primary graft function from delayed graft function or acute rejection in the early post transplantation period. We obtained 139 cadaveric and 19 living donor kidney core biopsies post reperfusion and 78 renal allograft biopsies taken because of graft dysfunction. RNA was isolated from tissue samples and mRNA encoding perforin, granzyme B or Fas ligand and a constitutively expressed cyclophilin B, a reference gene, was measured with the use of real-time quantitative polymerase chain reaction assay, and the levels of expression was correlated with allograft status. We did not find statistically significant differences in gene expression of perforin, granzyme B or Fas ligand among deceased and living donor kidneys and the mRNA expression of these cytotoxic molecules in donor kidney biopsies did not distinguish primary allograft function or early acute rejection. Significant differences were found between acute rejection (n=17) and zero-hour samples and acute rejection and non-rejection (n=41) samples for all 3 measured transcripts. No significant difference was found between acute borderline rejection (n=16) and non-rejection samples. In conclusion, effector molecules secreted by cytotoxic T lymphocytes were not activated in deceased donor kidneys and the genes did not classify the post-transplant course.

Kidney volume increases during long-term ciclosporin a treatment.

PURPOSE: Previously, we have for the first time reported enlargement of the pig kidney during long-term ciclosporin (CsA) treatment. In this paper, we summarize our findings of renal enlargement during long-term protocols with various dosages and durations of CsA administration as well as discuss possible pathogenetic mechanisms. MATERIALS AND METHODS: Twenty-two adolescent Gottingen minipigs were allocated into four groups: group A (n = 6) served as controls for 6 months; group B (n = 5) were treated with CsA (10 mg/kg per day) for 6 months, group C (n = 4), with CsA (20 mg/kg per day) for 6 months, and group D (n = 7) with CsA (10 mg/kg per day) orally for 12 months. At regular intervals, renal length and total volume were measured using magnetic resonance imaging; renal biopsies were performed for histological examination. RESULTS: A significant increase in kidney volume occurred in all CsA-treated pigs (groups B, C, and D); whereas the volume remained stable in the control animals (group A). A small but significant rise in kidney length was observed in groups A, B, and C, probably due to the normal growth of the animals. Histological examination was normal after treatment with CsA doses of 10 and 20 mg/kg per day for 6 months but showed definite interstitial fibrosis and glomerulosclerosis after treatment with 10 mg/kg per day CsA for 12 months. CONCLUSION: Long-term CsA treatment produced renal enlargement in pigs before the development of histological changes in the kidney. Thus, renal enlargement may represent an early stage of chronic CsA nephrotoxicity.

Changes in renal dimensions evaluated by magnetic resonance imaging and ultrasonography during long-term ciclosporin-A treatment.

PURPOSE: To investigate changes in renal dimensions during long-term treatment with ciclosporin-A (CsA). MATERIAL AND METHODS: Five mini-Göttingen pigs were treated with CsA (10 mg kg(-1) day(-1)) for 6 months; 3 untreated animals served as controls. Renal length was measured by magnetic resonance imaging (MRI) and ultrasonography (US); renal volume by MRI. Examinations were performed at baseline (0 weeks) and after the start of CsA treatment at intervals of 5 weeks (5-25 weeks). RESULTS: Comparison of baseline and end-point data (0 weeks vs. 25 weeks) revealed a statistically significant increase in renal volume in CsA-treated animals (87.1 cm3 vs. 55.9 cm3, P=0.002). Renal volume remained unchanged in the control group. A significant increase in renal length was found both in the CsA-treated pigs (MRI: 96 mm vs. 84 mm, P<0.001; US: 94 mm vs. 81 mm, P<0.001) and in the control group (MRI: 97 mm vs. 85 mm, P<0.001; US: 89 mm vs. 81 mm, P=0.018). No difference was found between MRI and US measurements based on 40 paired units (MRI variance: 2.4-30.3% and US variance: -5.1-40.6%, P=0.133). CONCLUSION: During long-term CsA treatment, renal volume increases in mini-pigs, but there is no correlation between the increase in volume and the increase in length in this pig model.

Chronic cyclosporine nephrotoxicity: a pig model.

Cyclosporine A (CsA) is one of the keystones in immunosuppressive treatment after solid organ transplantation, despite its major side effects such as nephrotoxicity. The chronic nephrotoxic effects of CsA seen in humans have been difficult to reproduce in small-animal models. The aim of the present study was to examine the chronic nephrotoxicity produced by therapeutic dosages of CsA in a pig model. Among 11 Gottingen minipigs included in the study, three died, yielding data from five animals given CsA (10 mg/kg/d, orally) for 6 months, and three controls. Body weight, blood pressure, glomerular filtration rate (GFR) by plasma clearance of (51)Cr-ethylenediamine-tetraacetic acid, CsA concentration, serum creatinine, and other values were measured every 5 weeks. Our results showed that the whole blood trough CsA levels were lower in pigs than in humans treated with similar CsA doses. Renal biopsies, which were obtained successfully, except one case of macroscopic hematuria, showed no histological changes in the kidney. No significant increase in serum creatinine or blood pressure was observed. Surprisingly, there was a significant increase in GFR during CsA treatment. We conclude that the pig model displays a hyperfiltration that warrants further investigation.

Does chronic low-dose treatment with cyclosporine influence the brain? A histopathological study in pigs.

Twenty percent of the patients immunosuppressed with cyclosporine A (CsA) develop neurological side effects such as tremor, paresthesias, headache, seizures, visual disorders, paresis, and coma-CsA encephalopathy. The encephalopathy resolves on CsA discharge; autopsies of recovered patients are normal. Characteristic lesions are seen on magnetic resonance imaging (MRI) during the period of encephalopathy. MRI of asymptomatic patients receiving CsA as well as most recovered patients are normal. Several theories of pathogenesis have been proposed, but none has been firmly established. The current placebo-controlled study, blinded to the investigator, was accordingly initiated to elucidate histopathological changes in the brain. Twelve adult Göttingen minipigs were randomized into two groups treated with either low-dose CsA (10 mg/kg/d) or no treatment for 6 months. Behavior, blood pressure, and blood parameters were measured throughout the study. All animals had a cerebral MRI before sacrifice. Three control pigs and one CsA-treated pig died during observation and were excluded from the study. None of the remaining eight pigs displayed behavioral signs or MRI-visible lesions characteristic of CsA encephalopathy. The brains appeared all normal on the gross pathological examination, but microscopy revealed perivascular, meningeal, and neuronal tissue infiltration with granulocytes and mononuclear cells in one CsA-treated pig, while the remaining pigs were without histopathological lesions. Pathological changes were noticed in one out of five CsA-treated animals, corresponding to the percentage of patients treated with CsA who develop CsA encephalopathy. To pursue this finding, two studies, one using CsA 20 mg/kg/d for 6 months and one using CsA 10 mg/kg/d for 12 months, have been initiated.

Relation between policies and work related assault: Minnesota Nurses' Study.

AIMS: To assess the relation between violence prevention policies and work related assault. METHODS: From Phase 1 of the Minnesota Nurses' Study, a population based survey of 6300 Minnesota nurses (response 79%), 13.2% reported experiencing work related physical assault in the past year. In Phase 2, a case-control study, 1900 nurses (response 75%) were questioned about exposures relevant to violence, including eight work related violence prevention policy items. A comprehensive causal model served as a basis for survey design, analyses, and interpretation. Sensitivity analyses were conducted for potential exposure misclassification and the presence of an unmeasured confounder. RESULTS: Results of multiple regression analyses, controlling for appropriate factors, indicated that the odds of physical assault decreased for having a zero tolerance policy (OR = 0.5, 95% CI 0.4 to 0.8) and having policies regarding types of prohibited violent behaviours (OR = 0.5, 95% CI 0.3 to 0.9). Analyses adjusted for non-response and non-selection resulted in wider confidence intervals, but no substantial change in effect estimates. CONCLUSIONS: It appears that some work related violence policies may be protective for the population of Minnesota nurses.

An epidemiological study of the magnitude and consequences of work related violence: the Minnesota Nurses' Study.

AIMS: To identify the magnitude of and potential risk factors for violence within a major occupational population. METHODS: Comprehensive surveys were sent to 6300 Minnesota licensed registered (RNs) and practical (LPNs) nurses to collect data on physical and non-physical violence for the prior 12 months. Re-weighting enabled adjustment for potential biases associated with non-response, accounting for unknown eligibility. RESULTS: From the 78% responding, combined with non-response rate information, respective adjusted rates per 100 persons per year (95% CI) for physical and non-physical violence were 13.2 (12.2 to 14.3) and 38.8 (37.4 to 40.4); assault rates were increased, respectively, for LPNs versus RNs (16.4 and 12.0) and males versus females (19.4 and 12.9). Perpetrators of physical and non-physical events were patients/clients (97% and 67%, respectively). Consequences appeared greater for non-physical than physical violence. Multivariate modelling identified increased rates for both physical and non-physical violence for working: in a nursing home/long term care facility; in intensive care, psychiatric/behavioural or emergency departments; and with geriatric patients. CONCLUSIONS: Results show that non-fatal physical assault and non-physical forms of violence, and relevant consequences, are frequent among both RNs and LPNs; such violence is mostly perpetrated by patients or clients; and certain environmental factors appear to affect the risk of violence. This serves as the basis for further analytical studies that can enable the development of appropriate prevention and control efforts.

Differences in family caregiver outcomes by their level of involvement in discharge planning.

Family caregivers play vital roles in assisting elders after they are released from the hospital. Although health care professionals advocate involving family caregivers in discharge planning for elders, little is known about the extent to which this involvement benefits or jeopardizes the caregiver's health and their perceptions of the caregiving experience. The purpose of this study was to determine whether the level of family caregiver involvement in discharge planning for an elder made a difference in caregiver health, discharge planning satisfaction, perception of care continuity, preparedness to assist the elder, and acceptance of the caregiving role 2 weeks and 2 months postdischarge. The sample consisted of 130 family caregivers for elders hospitalized with heart failure. Telephone interviews were conducted 2 weeks and 2 months postdischarge. The findings indicated that family caregivers who reported more involvement in discharge planning had significantly higher scores on satisfaction, feelings of preparedness, and perception of care continuity 2 weeks following the elder's hospitalization than those who reported little or no involvement in planning. Caregivers who reported more involvement in planning also were more accepting of the caregiving role. At 2 months postdischarge, caregivers who reported more involvement in discharge planning reported better health and more acceptance of the caregiving role than those who had little or no involvement in planning.

Predictors of elder and family caregiver satisfaction with discharge planning.

Client satisfaction is considered an important outcome measure in a managed care environment faced with escalating health care costs, shortened lengths of hospital stay, and competition among acute care hospitals. With shortened lengths of stay in acute care hospitals, discharge planning has assumed increased importance, particularly for elders who have chronic conditions, such as heart failure, that require follow-up care. Consequently, understanding the predictors of client satisfaction with discharge planning can help hospitals and their nursing staff to tailor services to meet client needs. Previous studies have focused on patient satisfaction with hospital care, with little attention given specifically to satisfaction with discharge planning and to family caregiver satisfaction with discharge planning. The purpose of this study was to determine whether there is a difference between elder and family member satisfaction with discharge planning 2 weeks after hospitalization and what factors predict satisfaction with discharge planning 2 weeks after hospitalization for elders hospitalized with heart failure and their family caregivers. Telephone interviews were conducted with 134 elder/family caregiver dyads 2 weeks after hospitalization. The results indicated that there were no statistically significant differences in discharge planning satisfaction of elders and their family caregivers. Continuity of care and extent to which they felt prepared to manage care following hospitalization were the best predictors of elder's and family caregiver's satisfaction with discharge planning.

A professional-patient partnership model of discharge planning with elders hospitalized with heart failure.

Despite efforts to improve the discharge planning process and subsequent outcomes, existing mechanisms fail to accurately identify elders' needs for follow-up care. Studies report rehospitalization rates ranging from 12 to 50%. The two aims of this study were to (1) examine the difference in outcomes for elders hospitalized with heart failure and caregivers who participated in a professional-patient partnership model of discharge planning compared to those who received the usual discharge planning and (2) examine differences in costs associated with hospital readmission and use of the emergency room following hospital discharge. A before-and-after nonequivalent control group design was used for this study. Data were collected from the control and the intervention cohorts before discharge and at 2 weeks and 2 months postdischarge. One hundred and fifty-eight patient-caregiver dyads completed both the predischarge and 2-weeks postdischarge interviews; 140 also completed a 2-month follow up. The average age of elders was 73.7 years; the average age of the caregivers was 58.5 years. The findings indicated that elders in the intervention cohort felt more prepared to manage care, reported more continuity of information about care management and services, felt they were in better health, and when readmitted spent fewer days in the hospital than the control cohort. Caregivers in the intervention cohort also reported receiving more information about care management and having a more positive reaction to caregiving 2 weeks postdischarge than the control cohort.

Managers' leadership and critical care nurses' intent to stay.

BACKGROUND: Cyclical fluctuations in turnover of critical care nurses are a large and complex problem. Managers' leadership characteristics may be a determinant of critical care nurses' intent to stay in the job. OBJECTIVE: To examine the direct and indirect effects of nurse-managers' characteristics of power, influence, and leadership style on critical care nurses' intent to stay in the nurses' employment positions. METHODS: The sample was 255 staff nurses in intensive care units at 4 urban hospitals. Established instruments with sound reliability and validity were used to assess the predictor, intervening, and outcome variables. Path analysis was used to examine the relationships in a conceptual model of intent to stay. RESULTS: The model explained 52% of the variance in intent to stay, and managers' characteristics were significant at each stage. Managers' position power and influence over work coordination had a direct link to intent to stay; structuring expectations and consideration contributed indirectly through the variables of instrumental communication, autonomy, and group cohesion. Instrumental communication, autonomy, and group cohesion decreased job stress and thus increased job satisfaction. Job satisfaction was directly linked with intent to stay. CONCLUSIONS: Inclusion of nurse-managers' characteristics explained more variance in intent to stay than did previous models. Managers with leadership styles that seek and value contributions from staff, promote a climate in which information is shared effectively, promote decision making at the staff nurse level, exert position power, and influence coordination of work to provide a milieu that maintains a stable cadre of nurses.

Research utilization and interdisciplinary collaboration in emergency care.

OBJECTIVES: To examine perceptions of nurse-physician collaboration and research utilization in a large, county medical center with an emergency medicine (EM) residency program, to assess differences among nurses, residents, and attending physicians, and to explore the relationship between collaboration and research utilization. METHODS: A cross-sectional, exploratory, correlational design. Questionnaires measuring four aspects of collaboration-leadership, communication, problem solving, and coordination-and four aspects of research utilization-support, attitude, availability, and use-were distributed to 115 nurses, 18 attending physicians, and 33 EM residents (n = 166). A 59% response rate was achieved. RESULTS: The survey instruments demonstrated acceptable reliability at 0.70 or better Cronbach's alpha except for communication timeliness (alpha = 0.64) and predictive validity. Overall, physicians and nurses rated measures of collaboration and research favorably. However, there were significant differences (p < 0.05) between physicians and nurses on four measures of collaboration (i.e., physician leadership, communication openness within group, communication openness between groups, and problem solving within group) and research utilization (research use), with physicians holding more favorable views than nurses. Three measures of collaboration predicted 47% of the variance in research use for physicians; only one measure of collaboration was important for nurses, explaining 9.3% of the variance in research use. CONCLUSION: Interdisciplinary collaboration showed some significance in promoting research use in the ED, especially for physicians. However, nurse-physician differences in perceptions of collaboration and research use should be examined more fully.

The Banff 97 working classification of renal allograft pathology.

BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation.

BACKGROUND: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation. METHODS: In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium. RESULTS: At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA. CONCLUSIONS: It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.

Interdisciplinary collaboration and discharge planning communication for elders.

The effects of personal characteristics and perceptions of interdisciplinary collaboration on discharge planning communication were examined for nurses, physicians, and social workers in two hospitals. The model for the study explained 61.7% of the variance in discharge planning communication for nurses. For all 142 health professionals, communication openness with social workers, problem solving between nurses and physicians, and collaboration with social workers were important to discharge planning communication. For nurses, communication satisfaction with patients and families also was important.

[Renal biopsy in connection with long-term treatment of psoriasis with cyclosporine]. / Nyrebiopsi i forbindelse med langtidsbehandling af psoriasis med ciclosporin.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CSA) therapy (range 2.5-6 mg/kg/day) of from six months to eight years. The study included pretreatment biopsies in 25 of the patients. After two years all biopsies shared features consistent with CSA nephropathy despite completely normal pretreatment morphology in 18 of the 25 patients. The severity of the findings, which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli, increased with length of therapy. Mild renal lesions were seen during the first two years. After four years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with the severity of the fibrosis. GFR studied in 14 patients six months to seven years after discontinuation of CSA was still significantly decreased in relation to baseline prior to therapy. The data from our study together with experiences from cardiac-transplanted patients indicate that patients with psoriasis, after two years therapy with CSA, should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Manager leadership and retention of hospital staff nurses.

This study used causal modeling to trace the effects of manager leadership characteristics on staff registered nurse (RN) retention in 4 urban hospitals. Unique to the study were the all-RN sample, using Leavitt's (1958) model of behavior within an organization to group variables, manager characteristics and unit structure variables as predictors, and focus on the work unit rather than the hospital. Effects of manager characteristics were traced to retention through work characteristics, job stress, job satisfaction, commitment, and intent to stay. Theoretical variables explained 22% of the retention variance. Manager consideration of staff and RN intent to remain directly affected retention; other variable effects passed through intent to stay. Different predictors were important to retention, unit separation, and turnover.

Renal biopsy findings in long-term cyclosporin treatment of psoriasis.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Effect of felodipine on renal function and vasoactive hormones in infrarenal aortic surgery.

We have examined the possible renoprotective effect of felodipine 5 mg orally, given daily for 5 days before operation, in 29 patients undergoing elective infrarenal aortic surgery in a randomized, blinded and placebo-controlled study. Effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urine output, fractional sodium clearance and plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide did not differ between the felodipine and placebo groups. ERPF and GFR were not reduced after operation in the placebo group. In the felodipine group, GFR was higher 24 h after operation compared with before operation. We conclude that increased GFR in the felodipine group, measured 24 h after operation, may indicate a beneficial effect of felodipine but in the present context this was not clinically important. Felodipine had no significant effect on vasoactive hormones.