Chronic fatigue syndrome: Features of a population of patients from northern Italy.

In this study we analyzed the clinical features of a population of Italian patients with chronic fatigue syndrome (CFS) diagnosed according to the CDC-1994 criteria. The aim was to investigate CFS patients and their relatives, in order to search for events related to the onset of the disease and to identify correlations with other diseases. The analysis was carried out by examining medical records belonging to 82 patients suffering from the syndrome. The documentation was collected between 2008 and 2011 and provided by the non-profit Italian organization AMCFS (Associazione Malati di CFS). The influence of gender on the age of onset and association with potential risk factors were investigated in patients and in their relatives. From the results a significant correlation between the age of onset and autoimmunity was observed.

Increase in peripheral benzodiazepine receptors on monocytes in fibromyalgia.

OBJECTIVE: The aim of this study is to evaluate the expression of Peripheral Benzodiazepine Receptors (PBRs) on leukocytes in patients affected by primary fibromyalgia and to argue their possible role in pain perception and in modulation of immunologic process. METHODS: The expression of PBRs has been evaluated by flow cytometry on monocytes, on lymphocytes and on granulocytes in twenty patients with primary fibromyalgia, with indirect immunofluorescence methods. RESULTS: Upregulation of leukocyte PBRs expression has been demonstrated in fibromyalgia. A statistically significant difference has been documented only in monocytes. The monocyte PBRs expression was 26.74 +/- 14.84 MIF in fibromyalgia versus 17.45 +/- 8.54 MIF in controls (P < 0.023). Upregulation of PBRs expression, although not statistically significant, was also observed in lymphocytes and granulocytes. CONCLUSIONS: The monocyte PBRs overincrease in fibromyalgia may be due to abnormalities in the regulation of pain or to inflammation. It might perhaps explicate the possible mechanisms of therapeutic response to benzodiazepine in fibromyalgia.

Effects of iloprost on adhesion molecules and F1 + 2 in peripheral ischemia.

BACKGROUND: Iloprost has beneficial effects on microcirculation by preventing platelet and leukocyte reciprocal activation, which is known to lead to endothelial damage and acute thrombosis. This drug also reduces inflammatory system activation by decreasing alpha M beta 2 integrin expression on the phagocyte membrane, might have a role in the protection and restoration of endothelial integrity and might interact with coagulation cascade activation. DESIGN: Forty patients were enrolled: 29 with systemic sclerosis (SSc) and 11 with peripheral artery disease (PAD). Iloprost was administered for 5 days in the first group and for 21 days in second group of patients. To ascertain whether iloprost modifies the parameters of endothelial and coagulation cascade activations, the plasma concentrations of S-ICAM-1 and F1 + 2 were detected in patients at baseline, after 5 days and, in PAD patients only, after 21 days of iloprost therapy. S-ICAM-1 is the endothelial counter receptor for alpha M beta 2 integrin and is a marker of endothelial cell activation; and F1 + 2 is a marker of coagulation cascade activation. RESULTS: After infusion of iloprost a significant decrease of S-ICAM-1 was observed in both the SSc (P < 0.002) and PAD patients (P < 0.004). Similarly, a significant decrease of F1 + 2 was observed in the SSc (P < 0.0004) and PAD patients (P < 0.003). CONCLUSIONS: The study provides evidence that iloprost reduces endothelial cells and coagulation cascade activations. Both of these mechanisms are responsible for improvement in microvascular functional capacity and for the long-term clinical benefit observed. After iloprost infusion, the SSc patients showed marked reductions in F1 + 2 and S-ICAM-1 concentrations that were statistically more significant relative to the PAD patients.

Increased production of inflammatory cytokines in patients with silent myocardial ischemia.

OBJECTIVES: The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exhibit any particular cytokine pattern. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient's perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors. METHODS: Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at -80 degrees C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-beta) and the proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta and -6). RESULTS: In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups. CONCLUSIONS: The data suggest that an "anti-inflammatory pattern" of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

Cigarette smoking and hypertension influence nitric oxide release and plasma levels of adhesion molecules.

Progression of atherosclerosis is currently believed to involve interactions between leukocytes and vascular endothelium. Epidemiological risk factors for atherosclerosis such as hypertension and smoking are known to cause endothelial dysfunction, which is an early event in the atherosclerotic process; they also may be considered in the light of their effects on adhesion molecule expression and release. Little is known about the additive effect between these two risk factors on endothelial adhesion molecule expression and nitric oxide release. Soluble adhesion molecules and the nitric oxide were quantified in smoking hypertensive patients in comparison to those from patients with hypertension alone. Cotinine, a stable metabolite of nicotine, has been used to identify smokers. One hundred and three hypertensive patients were selected: 51 smokers (plasma cotinine levels >25 ng/ml) and 52 non-smokers. Plasma concentrations of soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-I) were quantified with ELISA methods. Plasma concentration of nitric oxide metabolites was measured by HPLC, whilst plasma concentration of cotinine was measured by RIA. Significant increases of sICAM-1 and sVCAM-1 were demonstrated in smokers (p<0.001 and p<0.05, respectively). In the same patients, a positive significant correlation between sVCAM-1 and plasma cotinine levels was observed (p<0.002). Nitric oxide metabolites were reduced significantly (p<0.04) in smokers. In conclusion, our data show that the two risk factors, smoking and hypertension, are additive risk factors in generating endothelial dysfunction and vascular damage, which plays a key role in atherogenesis.

The effects of iloprost infusion on microcirculation is independent of nitric oxide metabolites and endothelin-1 in chronic peripheral ischaemia.

BACKGROUND: Endothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators. METHODS: Fourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2-/NO3-) and endothelin-1 (ET-1) plasma concentrations were detected; moreover, the endothelium-dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo-Doppler device. RESULTS: The echo-Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 +/- 17.49 vs. 310.71 +/- 36.32 s; P > 0.04). NO2-/NO3- and ET-1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected. CONCLUSION: This study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2-/NO3- or ET-1.

Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation.

The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.

Solitary extramedullary plasmacytoma.

A rare case of abdominal plasmacytoma is described. A computed guided biopsy of abdominal mass permitted an accurate diagnosis. Blood findings revealed an increased gamma-globulin level and serum immunoelectrophoresis revealed high IgG-kappa spike. Bone marrow biopsy resulted negative for neoplastic infiltration. Plasmacytoma is a malignant proliferation of differentiated B lymphocytes which produce immunoglobulin. In our case, microscopically, biopsy of abdominal mass revealed the presence of plasmablasts with bizarre multiforme nuclei, spindled contours and positive immunoenzymatic reaction for CD38, suggestive for plasma cell proliferation.

Lung-angiodysplasia and von Willebrand's disease in a family with Rendu-Osler disease. A case report.

A young woman suffering from sideropenic anemia, bleeding disorders related to von Willebrand's disease and pulmonary vascular telangiectasias presented at our observation. Laboratory findings, genetic and hemostatic studies revealed platelet aggregation defect while in her father and grandfather lung angiodysplastic lesions without platelet aggregation defect. The association between bleeding disorders and pulmonary angiodysplasia has rarely presented in literature and deficiency of von Willebrand factor might increase the risk of bleeding in patients with coexisting angiodysplastic disease.

Iloprost effects on phagocytes in patients suffering from ischaemic diseases: in vivo evidence for down-regulation of alpha M beta 2 integrin.

This study has been designed to demonstrate the in vivo effects of iloprost therapy on expression of adhesion molecules on phagocytes. Sixty patients suffering from peripheral arterial occlusive disease (PAOD) and/or from skin ulcers due to secondary progressive systemic sclerosis (PSS) were enrolled in a double-blind controlled parallel study. Thirty patients (group I) underwent iloprost infusion and 30 patients (group II) were treated with aspirin. Clinical assessment and measurement of phagocyte activation in vivo, using quantitative flow cytometry, were performed on entry and after 6 h on the first day of therapy. After 3 months of therapy, complete healing of all cutaneous lesions was observed in 84% of the patients treated with iloprost compared with the control patients (P < 0.001). Neutrophils and monocytes of PAOD and PSS patients showed a significant decrease in the expression of the alpha M beta 2 integrin adhesion receptor after 6 h of iloprost infusion. Neutrophils and monocytes released a lower amount of anion superoxide (O2-) after 6 h of iloprost treatment. These data confirm other clinical observations but demonstrate that in vivo this drug modifies the expression of the alpha M beta 2 integrin of phagocytes that has a key role in leukocyte-endothelium interactions in cases of inflammation and thrombosis.