Lymphoproliferative disorders in kidney transplant recipients: incidence, clinical characteristics and outcome

PURPOSE: The aim of this study was to determine the epidemiological and the clinical characteristics of post-transplant lymphoproliferative disease (PTLD) and to evaluate its impact on patients' and grafts' survival. PATIENTS AND METHODS: Three hundred and sixteen adult kidney recipients, transplanted between June 1986 and May 2006, were included. The incidence rates were calculated by dividing the number of different events (PTLD, death and graft-loss) by the total duration of follow-up. The survival rates and the cumulated frequency of PTLD were calculated according to the actuarial method. RESULTS: Seven recipients developed PTLD during a cumulated follow-up of 2202 years. The annual incidence was of 0.32% (95% CI : 0.30-0.34). It was of 0.81% (0.70-0.92) in recipients of kidneys from deceased donors, and of 0.25% (0.23-0.27) in patients transplanted from living donors (NS). The delay after transplantation for the diagnosis of PTLD ranged from 7.4 months to 7.7 years. PTLD was a B cell lymphoma in six cases and affected extra nodal sites in most of the cases. The treatment, comprising the cessation of immunosuppressive therapy in all cases, resulted in complete remission in four patients. Three patients died, representing an annual death rate of 6.1%, versus 2.8% in patients without PTLD (NS). The annual incidence of graft loss was 6.1% versus 3.2% among patients without PTLD (NS). CONCLUSION: PTLD was observed in 2.2% of our patients, with an annual incidence of 0.32%. It resulted in a decrease of both patients' and grafts' survivals. Preventive measures, including the improvement of the monitoring of immunosuppressive drugs and the prevention of viral infections, should be considered to reduce the risk of PTLD.     

Pathogenesis of systemic scleroderma: immunological aspects

Systemic sclerosis (SSc) is a connective tissue disorder that is characterized by excessive collagen synthesis by fibroblasts and by vascular hyperreactivity and obliteration phenomena. Excessive collagen production is the consequence of abnormal interactions between endothelial cells, fibroblasts and mononuclear cells. Immunological abnormalities are present very early in the development of SSc. Mononuclear cells, particularily macrophages and T lymphocytes play a prominent role in fibroblast activation and collagen synthesis through the cytokines they produce. Thus, lymphocytic infiltrates in the skin and in the lung are preferentially composed of CD8+ T lymphocytes, that produce important amounts of interleukin 4 (IL-4). The effects of IL-4 are added to these of transforming growth factor B (TGF-B) and connective tissue growth factor (CTGF) that stimulate collagen synthesis by fibroblasts. T lymphocytes produce important amounts of gamma interferon (INF-gamma) that is the best inhibitor of collagen synthesis by fibroblasts. However, the inhibitory effect of INF-gamma on collagen synthesis is diminished in SSc patients. Numerous autoantibodies can be evidenced in the serum of SSc patients. Three of them are specific for SSc and mutually exclusive: anti-centromere antibodies (Ab) in limited SSc, anti-Scl70 Ab in diffuse SSc and anti-RNA polymerase III Ab in diffuse SSc with renal involvement. These autoantibodies are good prognosis markers but their pathogenic role remains uncertain.     

Mobile right heart thrombus with minimal pulmonary embolism. A case report

The generalisation of the use of transthoracic echocardiography in the investigation of pulmonary embolism leads to the diagnosis of mobile right heart thrombus in about 5% of cases. A review of the literature shows that this association is mainly observed in clinically severe pulmonary embolism. The presence of a mobile right heart thrombus is associated with a poor prognosis and emergency treatment is based on thrombolytic therapy or surgical embolectomy. In minimal or infraclinical pulmonary embolism, the finding of a mobile right heart thrombus is rare and there is no consensus about its treatment. The authors report the case of a 61 year old man admitted to hospital for bilateral deep vein thrombosis with no symptoms of pulmonary embolism in whom investigations revealed a mobile right heart thrombus with minimal pulmonary embolism. The outcome was favourable with progressive resolution of the right heart thrombus with oral anticoagulation after three weeks of heparin therapy.     

Microscopic polyangiitis and polyarteritis nodosa: how and when do they start?

OBJECTIVE: To describe initial clinical symptoms attributable to microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN). METHODS: We retrospectively reviewed the medical files of 72 patients (mean followup 6.7 years) with biopsy-proven MPA (n = 36) or PAN (n = 36). RESULTS: Initial manifestations were similar in both entities except for peripheral neuropathy (P = 0.02) and gastrointestinal tract involvement (P = 0.006), which were significantly more frequent in PAN, and general signs alone in MPA (8%; P = 0.02). The mean time to diagnosis was 9.8 +/- 19.4 months; 35% of the patients died and 26% relapsed; significantly more MPA than PAN patients relapsed (P = 0.03). Time to diagnosis >/=90 days was associated with a trend toward more patients relapsing (P = 0.12), but not with an increased risk of mortality. CONCLUSION: Initial symptoms of MPA and PAN are usually nonspecific and last for several months before the diagnosis is made. A longer time to diagnosis is associated with a tendency to a higher relapse rate.     

Self-rated health among older adults: a cross-national comparison

Self-rated health (SRH) may have different implications in various social and cultural settings. However, few studies are available concerning SRH among older persons across countries. The aim of this study was to analyse whether there are cross-national differences in the association between status characteristics, several diseases common among older persons, activities of daily living (ADL), and SRH. The study base was the Comparison of Longitudinal European Studies on Aging (CLESA), which includes data from six population-based studies on aging conducted in Finland, Israel, Italy, The Netherlands, Spain and Sweden. The study population comprised 5,629 persons, with participants from all countries except Italy. Logistic regression analyses were used to assess the relationship between status characteristics, health conditions, ADL and SRH. To examine whether the association among status characteristics, health conditions, ADL and outcome differed across the CLESA countries, interaction terms defined as variable*country were considered separately for each variable. Regression analyses revealed that sex, education, lifetime occupation, heart disease and respiratory disease were differently distributed across countries. Among homogeneous factors, marital status (OR=1.21), hypertension (OR=1.41), stroke (OR=1.67), diabetes (OR=2.15), cancer (OR=1.47), musculoskeletal diseases (OR=2.44), and ADL (OR=2.72) turned out to be significantly associated with fair or poor SRH. The results indicate that there are differences in self-ratings of health across countries. These differences cannot be explained entirely by status characteristics, self-reported diseases or functional ability. However, an important finding was that in all countries most of the indicators of medical and functional health were homogeneously associated with SRH.     

Workplace bullying and violence as risk factors for type 2 diabetes: a multicohort study and meta-analysis

Aims/hypothesis

The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.

Methods

The study included 45,905 men and women (40–65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.

Results

Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.

Conclusions/interpretation

We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.

     

Renal amyloidosis secondary to hydatid cyst of the liver. Clinical remission after surgical excision

Revelation or risk of aggravation of renal amyloidosis after surgery has been published, particularly after pneumonectomy for tuberculosis. A few cases of improvement of renal amyloidosis following treatment of amylogenic focus have been published. We report the case of a 57 year-old woman who presented with nephrotic syndrome occurred twenty days after surgical resection of an hydatid cyst of the liver secondary to echinococcus granulosus. The renal biopsy showed deposits of amyloidosis. Amyloidosis typing (using anti AA sera) revealed an AA type. The patient received colchicine during nine years. A complete clinical remission of nephrotic syndrome was obtained four years after the surgical act. We discuss the association of hydatidosis and amyloidosis, surgery and amyloidosis, and remission of renal amyloid and colchicine therapy.     

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension

Aims/hypothesis Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by -tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats.Methods Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL--tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes.Results Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with -tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by -tocopherol treatment.Conclusions/interpretation We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.Abbreviations ROS Reactive oxygen species - TBARS thiobarbituric acids reactive substances - NO nitric oxide - STZ streptozotocin