Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients

BACKGROUND: The predictive value of clinical and renal histological features for renal outcome in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis was investigated in a prospective analysis of 96 patients with ANCA-associated vasculitis, and moderate renal involvement (creatinine <500 micromol/L). METHODS: The extent of 39 histological features in 96 biopsies (performed at entry in a clinical trial) was scored by two independent observers, according to a standardized protocol. Age, gender, diagnosis, glomerular filtration rate at entry (GFR0), ANCA-specificity, proteinuria, and treatment of these 96 patients were also taken into account. Treatment was standardized and started after the biopsy was performed. End-points included renal function at 18 months (GFR18), GFR18 corrected for GFR0 (CORGFR18), and the occurrence of relapse or death. RESULTS: Parameters that most strongly correlated with GFR18 were GFR0 (r = 0.67), interstitial fibrosis (r = -0.45), glomerulosclerosis (r = -0.37), and tubular atrophy (r = -0.36). Parameters that most strongly correlated with CORGFR18 were segmental (r = 0.45) and cellular (r = 0.30) crescents, and fibrinoid necrosis (r = 0.46). None of the clinical and histological features predicted the occurrence of relapse or death. By applying a stepwise linear multiple regression analysis, we designed a formula for the estimation of renal function at 18 months: GFR18 (mL/min) = 17 + 0.71 x GFR0 (mL/min) + 0.34 x fibrinoid necrosis (%) + 0.33 x segmental crescents (%), (r2 = 0.60; standard deviation = 19 mL/min). Our results were independent of diagnosis, ANCA-specificity, and treatment limb. CONCLUSIONS: These data suggest that in ANCA-associated glomerulonephritis, GFR0 and predominantly chronic renal lesions are potent predictors of GFR18. Active lesions are associated with renal function recovery and may be reversible. The formula for the estimation of GFR18 shows that a combination of GFR0 and renal histology is a better predictor for GFR18 than GFR0 only.     

Hypothesis: Iodine, selenium and the development of breast cancer

Background: In this paper we examine some of the evidence linking iodine and selenium to breast cancer development. Seaweed is a popular dietary component in Japan and a rich source of both of these essential elements. We hypothesize that this dietary preference may be associated with the low incidence of benign and malignant breast disease in Japanese women. In animal and human studies, iodine administration has been shown to cause regression of both iodine-deficient goiter and benign pathological breast tissue. Iodine, in addition to its incorporation into thyroid hormones, is organified into anti-proliferative iodolipids in the thyroid; such compounds may also play a role in the proliferative control of extrathyroidal tissues. Selenium acts synergistically with iodine. All three mono-deiodinase enzymes are selenium-dependent and are involved in thyroid hormone regulation. In this way selenium status may affect both thyroid hormone homeostasis and iodine availability. Conclusion: Although there is suggestive evidence for a preventive role for iodine and selenium in breast cancer, rigorous retrospective and prospective studies are needed to confirm this hypothesis.     

Changing social variations in self-assessed health in times of transition? The Baltic States 1994-1999

BACKGROUND: Dramatic social changes took place in the Baltic States (Estonia, Latvia and Lithuania) in the 1990s. This study investigates the extent to which social variations in self-assessed health changed during that period. METHODS: Norbalt Living Conditions Survey I (1994) and II (1999) random population-based samples in Estonia, Latvia and Lithuania were analysed. Associations of self-assessed health with six social dimensions (education, economic activity, car ownership, number of rooms, ethnicity and residence) were studied for males and females aged 25-74 years (n = 16 970). RESULTS: Substantial and significant associations with poor health were found for education, economic activity, car ownership and, to a lesser extent, number of rooms. Ethnic differences were found only among women in Estonia. By and large, social variations in health were comparable for most indicators between the three countries. Differences in self-assessed health were stable between 1994 and 1999, except for the relatively worse position of the economically non-active in 1999. CONCLUSIONS: Substantial social inequalities in self-assessed poor health exist in the Baltic States. Despite dramatic social changes taking place, social variations in self-assessed health have been rather stable in the second half of the 1990s. The economically non-active seem to have become more disadvantaged.     

Successful ablation of atrioventricular accessory pathway after cardiac transplantation

Liberalization of stringent guidelines regarding donor selection is acceptable in the case of critical recipient condition. Few cardiac allografts with preexisting accessory atrioventricular pathways have been implanted. We describe the successful radiofrequency modification of the atrioventricular node and ablation of an accessory pathway after cardiac transplantation. Although the previously healthy donor had no history of arrhythmia, the recipients postoperative course was characterized by multiple bouts of reentry tachycardia. The highly successful catheter-based ablation techniques available to cure this condition favor the use of donor hearts with a preexisting accessory pathway.     

Analysis of surgical versus medical therapy in active complicated native valve infective endocarditis

From 1972 to 1980, 23 patients (Group A) with native valve infective endocarditis underwent surgical intervention, often for multiple indications, during the active stage of the infective process because of progressive class III and IV (New York Heart Association) heart failure (12 patients), persistent severe hypotension (3 patients), uncontrolled infection for over 21 days (11 patients), aortic root abscess (2 patients), and pericarditis (1 patient). Eighty-five patients (Group B) with active native valve endocarditis, matched for severity of illness, were treated medically. Two patients (9%) in Group A and 43 patients (51%) in Group B died during the hospital admission (p < 0.001). Any difference in long-term cumulative survival rate between the 2 groups was largely due to the beneficial impact of surgical management on the hospital mortality. Of 23 patients in Group A, 11 (48%) had an entirely uncomplicated postoperative course. Long-term mortality rates in those with aortic valve endocarditis treated medically (79%) were significantly higher than in those with mitral valve involvement (47%) (p < 0.05). Patients with aortic valve involvement treated surgically had a better hospital (p < 0.005) and long-term (p < 0.005) survival rate than those treated medically. Two groups at risk for postoperative complications were identified; 3 of 11 patients (27%) with uncontrolled infection had an early postoperative recurrence, and 4 of 7 patients (57%) with an aortic root abscess had postoperative prosthetic paravalvular regurgitation.

Surgery therefore effects a substantial reduction in hospital mortality in patients with complicated active infective endocarditis (9% versus 51%), but patients with preoperative prolonged periods of uncontrolled infection or with aortic root abscess are liable to postoperative complications.     

Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition

Debate exists over the impact of caloric restriction (CR) on the level of energy expenditure. At the whole animal level, CR decreases metabolic rates but in parallel body mass also declines. The question arises whether the reduction in metabolism is greater, smaller or not different from the expectation based on body mass change alone. Answers to this question depend on how metabolic rate is normalized and it has recently been suggested that this issue can only be resolved through detailed morphological investigation. Added to this issue is the problem of how appropriate the resting energy expenditure is to characterize metabolic events relating to aging phenomena. We measured the daily energy demands of young and old rats under ad libitum (AD) food intake or 40% CR, using the doubly labeled water (DLW) method and made detailed morphological examination of individuals, including 21 different body components. Whole body energy demands of CR rats were lower than AD rats, but the extent of this difference was much less than expected from the degree of caloric restriction, consistent with other studies using the DLW method on CR animals. Using multiple regression and multivariate data reduction methods we built two empirical predictive models of the association between daily energy demands and body composition using the ad lib animals. We then predicted the expected energy expenditures of the CR animals based on their altered morphology and compared these predictions to the observed daily energy demands. Independent of how we constructed the prediction, young and old rats under CR expended 30 and 50% more energy, respectively, than the prediction from their altered body composition. This effect is consistent with recent intra-specific observations of positive associations between energy metabolism and lifespan and theoretical ideas about mechanisms underpinning the relationship between oxygen consumption and reactive oxygen species production in mitochondria.     

Cytokines and major depression

In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.