Comparison of the long-term survival benefits associated with revascularization or medical therapy in patients with known coronary artery disease undergoing transesophageal atrial pacing stress echocardiography

Although the utility of stress echocardiography for the diagnosis and prognostic evaluation of patients with suspected coronary artery disease (CAD) has been widely reported, few studies have evaluated the role of revascularization in relation to the presence of inducible ischemia during stress in patients with known CAD. The study population consisted of 295 consecutive patients who underwent transesophageal atrial pacing stress echocardiography (TAPSE) in the echocardiographic laboratory of our division between January 1988 and September 1997, in whom coronary angiography was performed within 10 days of the test. Patients were then assigned to revascularization or medical treatment according to the treatment given within 60 days of TAPSE. Cardiac-related deaths were higher in medically treated (19 of 135) than in revascularized (8 of 160) patients (p = 0.03). Parameters measured with TAPSE, i.e., positivity of the test, change in wall motion score index (DeltaWMSI and peak WMSI) were significantly related to mortality in medically treated patients but not in revascularized patients. At multivariate analysis, DeltaWMSI remained the most powerful predictor of cardiac death in medically treated patients (p = 0.005). Mortality progressively increased with increments in extent of inducible ischemia among medically treated patients (5 of 71 patients in DeltaWMSI 0, 3 of 27 in DeltaWMSI 0 to 25, 11 of 37 patients in DeltaWMSI >25) but not among revascularized patients (3 of 58 patients in DeltaWMSI 0, 2 of 51 in DeltaWMSI 0 to 25, 3 of 51 patients in DeltaWMSI >25). The survival curve in medically treated patients with ischemia in a remote zone (24 patients, 8 deaths) was worse than in other groups of medically treated patients (41 patients, 6 deaths). In conclusion, in patients with known CAD, the presence and extent of ischemia as evaluated with TAPSE worsens survival, if revascularization is not performed. In patients without ischemia at TAPSE, revascularization or medical therapy are equally effective.     

Long-term outcome of acute myocardial infarction treated with primary angioplasty. Experience of a public center in Alsatia-France

OBJECTIVES: Estimation of long-term outcome for patients suffering from acute myocardial infarction treated with primary angioplasty in an alsatian public center. PATIENTS AND METHODS: Two-hundred and ninety-eight patients who underwent an urgent coronarography in a non-university center, with a view to immediate angioplasty, between January 1999 and December 2001. RESULTS: Two-hundred and sixty-four patients (88.6%) were actually treated with urgent angioplasty, which has been successful in 87.1% of cases. Hospital mortality was of 7.7%. The population was composed of 16.4% patients older than 75 and of 11.7% patients with Killip 3 or 4 at admission. Mean follow-up was 34 months, lost to follow-up rate was of 4.7%. The global survival rate was of 78.9% and event-less survival rate of 41.9%. CONCLUSION: Our results confirm the efficiency of angioplasty in real-life conditions as well at short-term as at long-term.     

Primary Mediastinal La0rge B-Cell Lymphoma: A Single-Center Study of Clinicopathologic Characteristics

Primary mediastinal large B-cell lymphoma (PMLBCL) is a subset of LBCL with unique clinicopathologic features. Some studies have raised the question of differences in biological features and clinical course among patients from different parts of the world. We conducted a retrospective clinicopathologic analysis of 24 patients with PMLBCL from a single center in Croatia. We also conducted the first investigation of the frequency of lymphotropic viruses human herpesvirus 6 (HHV-6) and HHV-8 in lymphoid lesions of this disease. The clinical characteristics of the patients were as expected, with high International Prognostic Index scores, elevated serum lactate dehydrogenase (LDH) levels, and bulky disease being adverse prognostic factors. Only 6 patients (25%) showed CD30 expression, and Bcl-6 protein expression was, in our series, prognostically favorable (P = .0401). One patient's tumor had detectable HHV-6 genome sequence, but no HHV-8 sequences were detected in any tumors. Two thirds of the patients received CHOP chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone) with a relatively low complete remission rate (43.8%; median follow-up, 33.8 months). This study confirmed the moderate preponderance among PMLBCL patients of young females with B symptoms and elevated LDH levels. The CHOP regimen proved effective as first-line therapy only in patients with limited disease. Therefore, other third-generation chemotherapy protocols may be considered for treatment, especially in patients with bulky and advanced disease.     

An Italian study on psoriasis and depression

BACKGROUND: Psoriasis is often associated with the risk of physical disability, social discomfort and psychological disorders. OBJECTIVES: The aim of this study was to investigate the prevalence of depressive symptomatology among Italian patients with psoriasis vulgaris, in order to better evaluate the disease severity in this patient population. METHODS: Five thousand Italian patients with psoriasis were mailed the Center for Epidemiological Studies-Depression Scale (CES-D) questionnaire, a 20-item instrument developed to perform epidemiological studies of depressive symptomatology in the general population. Questionnaires with responses to 16 or more items were considered evaluable. RESULTS: We received evaluable questionnaires from 2,391 patients, including 1,528 men (63.9%) and 863 women (36.1%). Depressive symptomatology was observed in 1,482/2,391 patients (62% overall; females, 63%; males, 61%). Men < 40 years of age were significantly more likely to report depressive symptoms than were men > or =40 years of age (67 vs. 58%, respectively; p = 0.002). Depressive symptomatology was more prevalent in psoriatic patients with only primary or secondary education than in psoriatic patients with higher education (51 vs. 32%, respectively; p < 0.02). CONCLUSION: Our results are consistent with previous studies showing that psoriasis is associated with profound psychological morbidity, in particular with depression in a large number of patients. It is important to consider this association in the overall management of psoriasis.     

Anaplastic oligodendroglioma and gliomatosis type 2 in interferon-beta treated multiple sclerosis patients. Report of two cases

The concurrence of multiple sclerosis (MS) and brain tumors has been reported, but it is not known whether MS patients are at greater risk of harbouring the latter. The most common cerebral neoplasms reported in MS patients were oligodendroglioma, astrocytoma, glioblastoma and gliomatosis. MS can also present as a mass lesion that mimics a brain tumor. To establish the correct diagnosis radiological follow-up and/or histological confirmation is needed. Two cases of coincidental MS and brain tumors are reviewed. One is a 26-year-old woman with relapsing-remitting MS and an anaplastic oligodendroglioma, the other a 49-year-old woman patient with relapsing-remitting MS and gliomatosis type 2. Both patients were treated with interferon-beta1b and both died from the tumor. The concurrence of MS and brain tumors could be purely coincidental, or the result of neoplastic transformation of reactive glial cells in the areas of demyelination. The combination of a brain tumor and MS, and interferon-beta treatment could also be pure coincidence or an unknown side effect of treatment. Although interferon-beta has been said to function as a tumor-suppressor protein, the influence of long-term treatment of MS patients on cancer development is not known.     

Endogenous leukemia inhibitory factor attenuates endotoxin response

Leukemia inhibitory factor (LIF) is induced in inflammation and likely plays a regulatory role. Using LIF-deficient mice (LIF-/-), we report here that endogenous LIF has a protective role in endotoxic shock and host defence. LIF-/- mice have heightened sensitivity to LPS in a LPS/D-galactosamine (D-Gal) sensitization model compared to wild-type mice (LIF+/+), enhanced thrombocytopenia and leukopenia, with increased hepatic necrosis, neutrophil sequestration in the lung and accelerated mortality. These findings correlated with 10-fold higher tumour necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) serum levels and reduced IL-10 production in LIF-/- mice in response to LPS. Therefore, endogenous LIF attenuates the endotoxic shock response, enhances the expression of basal acute phase proteins and IL-10 production, which downregulates TNFalpha synthesis and release and thereby confers partial protection to endotoxemia.     

Three-dimensional quantitative magnetisation transfer imaging of the human brain

Quantitative magnetisation transfer (MT) analysis is based on a two-pool model of magnetisation transfer and allows important physical properties of the two proton pools to be assessed. A good signal-to-noise ratio (SNR) for the measured signal is essential in order to estimate reliably the parameters from a small number of samples, thus prompting the use of a sequence with high SNR, such as a three-dimensional spoiled gradient acquisition. Here, we show how full brain coverage can be accomplished efficiently, using a three-dimensional acquisition, in a clinically acceptable time, and without the use of large numbers of slice-selective radio-frequency pulses which could otherwise confound analysis. This acquisition was first compared in post mortem human brain tissue to established two-dimensional acquisition protocols with differing SNR levels and then used to collect data from six healthy subjects. Image data were fitted using the two pool model and showed negligible residual deviations. Quantitative results were assessed in several brain locations. Results were consistent with previous single-slice data, and parametric maps were of good quality. Further investigations are needed to interpret the regional variation of quantitative MT quantities.     

DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's disease

Senile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the brain of Alzheimer's disease (AD) patients. NFT are mainly composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly. Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function, thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no effect on the individual genetic risk for AD.     

Role of cytokines and chemokines in the regulation of innate immunity and HIV infection

The earliest defense against microbial infection is represented by the responses of the innate (or natural) immune system, that also profoundly regulates the adaptive (or acquired) T- and B-cell immune responses. Activation of the innate immune system is primed by microbial invasion in response to conserved structures present in large groups of microorganisms (LPS, peptidoglycan, double-stranded RNA), and is finely tuned by different cell types (including dendritic cells, macrophages, natural killer cells, natural killer T cells, and gammadelta T cells). In addition, several soluble factors (complement components, defensins, mannose-binding lectins, interferons, cytokines and chemokines) can play a major role in the regulation of both the innate and adaptive immunity. In this review, we will briefly overview the regulation of some cellular subsets of the innate immune system particularly involved in human immunodeficiency virus (HIV) infection and then focus our attention on those cytokines and chemokines whose levels of expression are more profoundly affected by HIV infection and that, conversely, can modulate virus infection and replication.