In-stent restenosis of the renal artery in a single kidney patient: the role of ACEI in the therapeutic choice

Renal artery stenosis (RAS) caused by atherosclerotic changes of the renal arteries has become a concern as a cause of end-stage renal failure. Percutaneous balloon angioplasty with or without endovascular stenting is an increasingly accepted procedure at the expense of classical approaches such as aortorenal bypass and other types of surgery. Renal percutaneous transluminal angioplasty and stenting (RPTAS) represent the first therapeutic choice; however, there is doubt regarding the satisfactory long-term outcome for primary RPTAS. Currently, there is no clear evidence whether or not RPTAS prevents further progressive renal function decline because comparisons between interventional randomized studies and medical therapy are still lacking. Despite the fact that the use of angiotensin-converting enzyme inhibitors (ACEIs) may be a potential cause of acute renal failure, clinical data suggest that ACEI therapy is associated with better survival in patient with RAS. In our case, the use of ACEIs has been fundamental for the indirect evaluation of restenosis degree and RPTAS.     

Antithrombin after cardiac surgery: implications on short and mid-term outcome

Backgrounds Antithrombin (AT) drop during cardiac surgery has been described. The causes and the effects of this phenomenon are not clear. The objective of the study is to evaluate the relationship of AT postoperative values on short and mid-term outcome after cardiac surgery. Methods Between January and June 2005, 405 patients, who underwent cardiac operations at our Institution had AT values available preoperatively and postoperatively. Using Receiver Operating Characteristic curves, a cut-off equal to 63.7% for ICU-arrival AT was chosen in order to divide the entire population in two groups (117 patients with ICU-arrival AT < 63.7%, Low AT group, and 288 patients with ICU-arrival AT ≥ 63.7%, High AT group). Objective of the study was to evaluate the predictive role of ICU-arrival AT < 63.7% on in-hospital mortality and morbidity and on 18 months follow-up after cardiac surgery. Results ICU-arrival AT was significantly lower than preoperative AT (90.7 ± 16.3% vs. 71.2 ± 15.1%, P < 0.0001). Patients in the Low AT group were older, more often female, had a worse Euroscore and required longer CPB duration and cross clamp time. They had significantly higher preoperative and postoperative d-dimer levels. ICU arrival AT < 63.7% was not associated with increased in-hospital mortality but it was an independent risk factor for longer mechanical ventilation, need of inotropic support, excessive bleeding and blood products transfusion. ICU arrival-AT < 63.7% was associated with worse survival during 18 months follow up (92.3% vs. 85.4% in the High AT and Low AT group, respectively, P = 0.05). Conclusions Low AT after cardiac surgery is associated with higher incidences of peri-operative complications and worse survival in the mid-term. Future studies should clarify the pathophysiologic mechanism of this findings and possible therapeutic directions.     

Characterization of tau pathologies in gray and white matter of Guam parkinsonism-dementia complex

Guam parkinsonism-dementia complex (PDC) is a neurodegenerative tauopathy in ethnic Chamorro residents of the Mariana Islands that manifests clinically with parkinsonism as well as dementia and is characterized neuropathologically by prominent cortical neuron loss in association with extensive telencephalic neurofibrillary tau pathology. To further characterize cortical gray and white matter tau, alpha-synuclein and lipid peroxidation pathologies in Guam PDC, we examined the brains of 17 Chamorro PDC and control subjects using biochemical and immunohistological techniques. We observed insoluble tau pathology in both gray and white matter of PDC and Guam control cases, with frontal and temporal lobes being most severely affected. Using phosphorylation dependent anti-tau antibodies, abundant tau inclusions were detected by immunohistochemistry in both neuronal and glial cells of the neocortex, while less alpha-synuclein pathology was observed in more limited brain regions. Further, in sharp contrast to Alzheimer’s disease (AD), levels of the lipid peroxidation product 8, 12–iso-iPF_2α-VI isoprostane were not elevated in Guam PDC brains relative to controls. Thus, although the tau pathologies of Guam PDC share similarities with AD, the composite Guam PDC neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF_2α-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs), which may imply that Guam PDC and FTD tauopathies share underlying mechanisms of neurodegeneration.     

Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection

In this study, we demonstrate that the in vitro interactions between a CD56(neg)/CD16(pos) (CD56(neg)) subset of natural killer (NK) cells and autologous dendritic cells (DCs) from HIV-1-infected viremic but not aviremic individuals are markedly impaired and likely interfere with the development of an effective immune response. Among the defective interactions are abnormalities in the process of reciprocal NK-DC activation and maturation as well as a defect in the NK cell-mediated editing or elimination of immature DCs (iDCs). Notably, the lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after the complete masking of major histocompatibility complex I molecules, suggesting that the defective elimination of autologous iDCs is at the level of activating NK cell receptors. In this regard, the markedly impaired expression/secretion and function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among the CD56(neg) NK cell subset, largely accounts for the highly defective NK cell-mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic but not aviremic patients are substantially impaired in their ability to secrete interleukin (IL)-10 and -12 and to prime the proliferation of neighboring autologous NK cells, which, in turn, fail to secrete adequate amounts of interferon-gamma.     

Biofilm formation by the emerging fungal pathogen Trichosporon asahii: development, architecture, and antifungal resistance

Trichosporon asahii is the most common cause of fatal disseminated trichosporonosis, frequently associated with indwelling medical devices. Despite the use of antifungal drugs to treat trichosporonosis, infection is often persistent and is associated with high mortality. This drove our interest in evaluating the capability of T. asahii to form a biofilm on biomaterial-representative polystyrene surfaces through the development and optimization of a reproducible T. asahii-associated biofilm model. Time course analyses of viable counts and a formazan salt reduction assay, as well as microscopy studies, revealed that biofilm formation by T. asahii occurred in an organized fashion through four distinct developmental phases: initial adherence of yeast cells (0 to 2 h), germination and microcolony formation (2 to 4 h), filamentation (4 to 6 h), and proliferation and maturation (24 to 72 h). Scanning electron microscopy and confocal scanning laser microscopy revealed that mature T. asahii biofilms (72-h) displayed a complex, heterogeneous three-dimensional structure, consisting of a dense network of metabolically active yeast cells and hyphal elements completely embedded within exopolymeric material. Antifungal susceptibility testing demonstrated a remarkable rise in the MICs of sessile T. asahii cells against clinically used amphotericin B, caspofungin, voriconazole, and fluconazole compared to their planktonic counterparts. In particular, T. asahii biofilms were up to 16,000 times more resistant to voriconazole, the most active agent against planktonic cells (MIC, 0.06 microg/ml). Our results suggest that the ability of T. asahii to form a biofilm may be a major factor in determining persistence of the infection in spite of in vitro susceptibility of clinical isolates.     

Carbamazepine-responsive paroxysmal nausea and vomiting in a patient with meningeal carcinomatosis

In neurology, paroxysmal syndromes are well-known, eg, as manifestations of multiple sclerosis. We report a patient with meningeal carcinomatosis, who presented with therapy-refractory nausea and vomiting. The clinical suspicion of a paroxysmal syndrome prompted a trial of carbamazepine, which resulted in complete cessation of the symptoms. In cancer patients with central nervous system (CNS) involvement and therapy-refractory symptoms with sudden onset, carbamazepine treatment should be considered.     

Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.     

Risk and predictors of motor-performance decline in a normally functioning population-based sample of elderly subjects: the Italian Longitudinal Study on Aging

OBJECTIVES: To examine risk and predictors of motor-performance (MP) decline targeting subjects performing normally at an initial observation. DESIGN: Cohort study. SETTING: A subsample of the Italian Longitudinal Study on Aging (aged 65-84). PARTICIPANTS: One thousand fifty-two subjects (mean age+/-standard deviation = 71+/-5, 69% men) with normal MP at baseline. MEASUREMENTS: Six tests (standing up from a chair, stepping up, tandem walk, standing on one leg, walking speed, and steps turning 180 degrees ) were used to assess MP at baseline and after 3 years. Baseline characteristics were potential predictors of MP decline. RESULTS: Of the 1,052 subjects performing normally at baseline, 166 (15.8%) had declined in MP at follow-up. Older age, female sex, lower education, symptoms of distal symmetrical neuropathy, cognitive impairment without dementia, parkinsonism, heart failure, anemia, depressive symptoms, worse Mini-Mental State Examination score, and lost activities of daily living and instrumental activities of daily living (IADLs) were significantly associated with MP decline in univariate comparisons. Older age (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 2.14-6.88 comparing age classes > or =80 with 65-69), female sex (OR=1.50, 95% CI = 1.03-2.20), distal symmetric neuropathy (OR = 2.00, 95% CI = 1.03-3.87), depressive symptoms (OR = 1.85, 95% CI = 1.17-2.24), and baseline IADLs (OR = 1.22, 95% CI = 1.08-1.37 for each lost activity) independently predicted MP decline after regression analysis. CONCLUSION: In a population-based cohort of elderly people with normal MP, one-sixth declined in 3 years. Age, sex, distal symmetrical neuropathy, depressive symptoms, and baseline IADLs independently predicted this decline. Distal symmetrical neuropathy is underestimated in the clinical and epidemiological evaluation of motor decline in older people.     

Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma

Vascular endothelial growth factor165 (VEGF165) and semaphorin3A (SEMA3A) elicit pro- and antiangiogenic signals respectively in endothelial cells (ECs) by binding to their receptors VEGFR-2, neuropilin-1 (NRP1), and plexin-A1. Here we show that the VEGF165-driven angiogenic potential of multiple myeloma (MM) ECs is significantly higher than that of monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs) and human umbilical vein (HUV) ECs. This is probably due to a constitutive imbalance of endogenous VEGF165/SEMA3A ratio, which leans on VEGF165 in MMECs but on SEMA3A in MGECs and HUVECs. Exogenous VEGF165 induces SEMA3A expression in MGECs and HUVECs, but not in MMECs. Moreover, by counteracting VEGF165 activity as efficiently as an anti-VEGFR-2 antibody, exogenous SEMA3A restrains the over-angiogenic potential of MMECs. Our data indicate that loss of endothelial SEMA3A in favor of VEGF165 could be responsible for the angiogenic switch from MGUS to MM.