The role of 3D and speckle tracking echocardiography in cardiac amyloidosis: a case report.

Cardiac amyloidosis (CA) is a disorder characterized by amyloid fibrils deposition in cardiac interstitium; it results in a restrictive cardiomyopathy with heart failure (HF) and conduction abnormalities. The "gold standard" for diagnosis of CA is myocardial biopsy but possible sampling errors and procedural risks, limit it's use. Magnetic resonance (RMN) offers more information than traditional echocardiography and allows diagnosis of CA but often it's impossible to perform. We report the case of a man with HF and symptomatic bradyarrhythmia that required an urgent pacemaker implant. Echocardiography was strongly suggestive of CA but wasn't impossible to perform an RMN to confirm this hypothesis because the patient was implanted with a definitive pacemaker. So was performed a Speckle Tracking Echocardiography (STE) and a 3D echocardiography: STE allows to differentiate CA from others hypertrophic cardiomyopathy by longitudinal strain value < 12% and 3D echocardiography shows regional left ventricular dyssynchrony with a characteristic temporal pattern of dispersion of regional volume systolic change. On the basis of these results, finally was performed an endomyocardial biopsy that confirmed the diagnosis of CA. This case underlines the importance of news, noninvasive techniques such as eco 3D and STE for early diagnosis of CA, especially when RMN cannot be performed.

Cranial osteolytic metastases as the only recurrence of gastric carcinoma.

The purpose of this case report is to increase the knowledge about bone metastatic pattern in gastric cancer. A 59-year-old man presented with headache three years after a total gastrectomy for signet-ring cell carcinoma. Head computed tomography and magnetic resonance imaging showed multiple osteolytic lesions of the cranial vault and base, consistent with metastatic or haematological disease. Bone scintigraphy confirmed areas of accumulation only in the skull. An extensive search didn't show any other tumor. Bone biopsy revealed metastatic signet-ring cell carcinoma. In gastric cancer, bone metastases are generally associated with metastases in lymph nodes, liver, and lung, and have a higher frequency in the thoracolumbar spine. However, cranial bone metastases presenting with headache may be the only manifestation of gastric cancer recurrence.

Refractory Takayasu arteritis successfully treated with infliximab.

Takayasu arteritis (TA) is a chronic inflammatory disease of large arteries which progressively develop stenosis, occlusion or aneurismal degeneration. Proinflammatory cytokines and, among these, tumor necrosis factor-alpha (TNF-alpha) are increased and play a pathogenetic role in the development of disease. Conventional therapy often fails to determine clinical remission and, in these cases, pathogenetic strategies with anti-TNF-alpha drugs have been proposed. Infliximab is a human-murine chimeric monoclonal antibody that specifically binds to and neutralizes soluble TNF-alpha. It is an effective treatment for rheumatoid arthritis, spondyloarthritis, Crohn's disease and ulcerative colitis and it has been recently proposed for the treatment of TA in patients refractory to conventional therapy. Here we report the case of a patient affected by Takayasu arteritis unresponsive to conventional therapy who was then treated with infliximab and obtained a clinical remission of the disease.

Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia.

BACKGROUND: Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. MATERIALS AND METHODS: A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10-40 mg day(-1)) to reach the appropriate Adult Treatment Panel-III LDL target of 3.36 mmol L(-1). Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3'UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique. RESULTS: LOX-1 3'UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4.90, 95% CI 3.19-6.98, P < 0.00001). Smoking influenced events in LDL-targeted subjects (P < 0.0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3'UTR/C genotype regardless of the magnitude of LDL reduction (OR 4.21, 95% CI 2.29-6.70 P < 0.0001). CONCLUSIONS: LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity.

Increased TNF-alpha production by peripheral blood mononuclear cells in patients with Krabbe's disease: effect of psychosine.

BACKGROUND: Inflammatory and/or immune activation occurs both in animal models (twitcher mice) and in the brain of patients with Globoid cell leukodystrophy (GLD) or Krabbe's disease (KD). In this study we evaluated in vitro the cytokine profile of KD patients and the effect of psychosine, the toxic metabolite which plays a role in the demyelination process in these patients. MATERIALS AND METHODS: We studied cytokine production by peripheral blood mononuclear cells (PBMCs) isolated from four KD patients, diagnosed on the basis of clinical criteria. Cells were cultured and stimulated with appropriate agents and the supernatants collected before and after the addition of psychosine. Tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and monocyte chemoattractant factor (MCP)-1) production was evaluated (ELISA method) and compared with a group of 10 normal subjects. RESULTS: We found a significant increase of TNF-alpha release by PBMCs of KD patients compared with healthy subjects; TNF-alpha production was significantly increased after LPS addition. Psychosine was able to induce a further significant increase (P < 0.05) only in cells obtained from KD patients and not from control subjects. No changes were found in IL-8 and MCP-1 production. CONCLUSIONS: The increased TNF-alpha production permits us to confirm the presence of an inflammatory-immune stimulus in KD patients, which may be induced and potentiated by the pathogenetic metabolite psychosine.

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes.

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNgamma and TNFalpha production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.

Cytokines in acute coronary syndromes.

The aim of this study was to show the presence of an imbalance between pro-inflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, which are well known to possess pro-inflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity, in two groups of 30 patients affected by acute myocardial infarction (AMI) and unstable angina (UA), compared with two equivalent groups of patients with stable angina (SA) and of healthy volunteers. We found a significant increase of IFNgamma and TNFalpha production (p<0.01) and a significant decrease of IL-10 production (p<0.01) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes were found between AMI and UA patients and SA patients and controls. We conclude that a relevant imbalance in cytokine release is present in ACS, markedly favoring pro-inflammatory effects.

Chronic urticaria and blastocystis hominis infection: a case report.

We report a case of a 45 year old woman which fulfilled the criteria of chronic urticaria (remitting and relapsing bouts of erythematous and pruriginuos lesions without angioedema, lasted four months). Cutaneous manifestations were not related to a specific inducing factor, had no benefit from antihystamine and steroid drugs and were associated sometimes with mild gastroentric disorders. Patient was submitted to extensive clinical, laboratory and intrumental investigations which permit to exclude many conditions: allergy to inhalants, food, insects and drug adverse reactions, autoimmune urticaria, autoimmune diseases, neoplastic and infectious diseases. Finally coprocolture disclosed the presence of Blastocystis hominis in stool samples thus permitting to associate urticaria to parasitic infection. Both cutaneous manifestations and mild abdomen disturbs disappeared after appropriate treatment. Despite the high diffusion the aetiopathogenesis of chronic urticaria remains often undefined. A large number of parasites have been correlated with urticaria but few data exist as regards Blastocystis hominis infection; then our findings may add evidence to the role of this parasite in inducing chronic urticaria. Considering that Blastocystis hominis is a modest pathogen for humans, the mechanism is probably the typical one of cutaneous allergic hypersensitivity; antigen parasites induce the activation of specific clones of Th2 lymphocytes, the release of related cytokines and the consequent IgE production.

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

BACKGROUND: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation. METHODS: Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment. RESULTS: PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05). CONCLUSIONS: The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

T cell activation and enhanced apoptosis in non-ST elevation myocardial infarction.

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Cardiac papillary fibroelastoma: an unusual source of cerebral embolism solved with local fibrinolysis.

Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before echocardiography, it was an occasional autoptic finding. With the development of ultrasonographic techniques, it is currently possible to carry out diagnosis in vivo. We report the case of a young woman with cerebral ischemia who was successfully treated by intra-arterial fibrinolysis with complete clinical resolution. Transesophageal echocardiography (TEE) identified a papillary fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of the tumor was performed. Sudden cerebral or peripheral embolization is frequently linked to thrombotic material which surrounds the neoplasm, and thus can be successfully treated with local fibrinolysis.

Different mechanisms of fibrinolysis impairment among dyslipidemic subjects.

To determine whether there is a correlation between fibrinolytic activity and dyslipidemia, we performed a study of 72 subjects (20 patients with hypercholesterolemia, 20 with hypertriglyceridemia, 12 with isolated low high-density lipoprotein (HDL)-cholesterol (mean age 47.7 +/- 6.3, body mass index 24.7 +/- 0.4) and 20 healthy controls. Plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were detected at baseline and after venous occlusion test. We also measured at baseline lipidic pattern, soluble E and P selectins (sE-sel, sP-sel), prothrombin factor 1+2 (F1+2), lipoprotein(a), factor VII, plasma insulin, fibrinogen, homocysteine, and thrombin activable fibrinolysis inhibitor (TAFI) activity. Fibrinolysis was significantly reduced in hypertriglyceridemic patients compared with hypercholesterolemic patients and control subjects (PAP, p < 0.01 and p < 0.001) and was associated with increased PAI-1 (at baseline and after venous occlusion test, p < 0.001). sP-sel, F1 +2 and TAFI were not significantly different compared with controls, while hypercholesterolemic subjects showed a significant increase in these parameters (p < 0.001), which were related to decreased PAP only at the upper low-density lipoprotein (LDL)-cholesterol levels (>160 mg/dl) (p < 0.001, r = -0.76). Moreover, there was no significant difference in PAI-1 activity (at baseline and after venous occlusion test) compared with controls. In conclusion, endothelial dysfunction was the main mechanism of decreased fibrinolysis in subjects with hypertriglyceridemia and low HDL-cholesterol, while enhanced thrombin generation and TAFI activity were the main determinants in hypercholesterolemia.

Systemic adenosine increase during cold pressor test is dependent on sympathetic activation.

1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous nucleoside adenosine (ADO) has been suggested to play a relevant role by contributing to sympathetic stimulation. The possibility was investigated that CPT-induced increases in plasma ADO levels were not only an expression of the increased production of ADO in the ischaemic area, but also a consequence of systemic sympathoexcitatory mechanisms, thus showing a bidirectional involvement of the mechanisms of ADO formation. 2. The CPT was performed in 15 volunteers and mean arterial blood pressure (MABP) and HR were evaluated, together with plasma levels of noradrenaline (NA) and ADO in the tested and contralateral arm. The 15 subjects were then divided into three groups of five that were treated with either 5 mg transdermal clonidine weekly, 100 mg atenolol daily or 600 mg aminophylline twice daily. After 1 week treatment, the same test was repeated in the respective groups. 3. The CPT induced a rise in MABP and HR and an increase in plasma levels of NA and ADO. Increases in ADO were more pronounced in the tested arm. Clonidine blunted the haemodynamic response and NA release, while increases in ADO increase were reduced to a greater extent in the contralateral arm rather than the tested arm. Atenolol only affected MABP and HR without any effect on NA and ADO levels. Theophylline did not show any effect on CPT-induced changes. 4. In conclusion, local vasoconstriction and ischaemia induced in one arm following CPT are associated with haemodynamic changes dependent on the activation of the sympathetic system. The observed increase in plasma levels of ADO seems to be, in part, a direct expression of local responses to ischaemia (pre-dominant in the tested arm), but also appears as the consequence of systemic sympathoexcitatory mechanisms. Such increases in ADO are not dependent on a beta 1-adrenoceptor-mediated mechanism. Finally, theophylline, at a therapeutic dose, has no effect on the response to CPT.

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis.

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.

Polymyositis-like syndrome in hypothyroidism: report of two cases.

An increase of muscle enzymes in hypothyroidism has sometimes been correlated with a polymyositis-like syndrome and hypothyroid patients have been misdiagnosed and mismanaged as suffering from polymyositis. Actually, muscle symptoms, such as aches and pain, stiffness, weakness and cramps or, more rarely, hypertrophy, are observed in hypothyroidism and increased serum muscle enzyme values, particularly the level of creatine phosphokinase (CPK), indeed seem to suggest polymyositis. The muscular groups most commonly affected by the above mentioned symptomatology are those of the shoulder and pelvic girdles. In this report two hypothyroid patients complaining of muscle symptoms, whose serum muscle enzymes were particularly elevated, are described. In the first case the patient had been suffering from pain and weakness of the thenar eminence for about 4 months. The clinical features suggested a diagnosis of Carpal Tunnel Syndrome, but thyroid function tests revealed primary hypothyroidism. In the second case the patient had been afflicted with muscular weakness of the shoulder girdle for 2 months and was unable to keep his arms raised over his head. A study of thyroid function demonstrated a picture of hypothyroidism. Both patients were treated with L-thyroxine and in a relatively short time biochemical parameters improved remarkably, and the symptoms disappeared. The hypothesis that a muscular effort of long duration by hypothyroid patients may have been responsible for the muscular damage and the symptoms may explain why only a few hypothyroid patients develop a clinical picture similar to polymyositis.

Double-blind comparison of the efficacy and safety of etodolac SR 600 mg u.i.d. and of tenoxicam 20 mg u.i.d. in elderly patients with osteoarthritis of the hip and of the knee.

Etodolac SR is the sustained-release formulation of etodolac, an effective anti-inflammatory drug used in the treatment of various rheumatic diseases. The efficacy and safety of etodolac SR were compared with those of tenoxicam in 120 elderly patients with radiographic and clinical evidence of active osteoarthritis (OA) of the knee and/or the hip. This was a double-blind, double-dummy, randomized, parallel-group, multicentre study conducted at 4 Italian rheumatic-disease units. Sixty patients received 600 mg of etodolac SR once daily (u.i.d.) for 8 weeks; the remaining 60 patients received 20 mg of tenoxicam u.i.d. Significant improvements in all 6 efficacy parameters (viso-analogic scale of the global pain, pain at active movements, night pain, joint tenderness, joint motility, and Lequesne's algofunctional index) were observed within each of the treatment groups even after the first 2 weeks of therapy. There were no significant differences in the therapeutic response between the two groups for any efficacy parameters. Adverse reactions, mostly regarding the G-I tract, were significantly more frequent in the tenoxicam group than in the etodolac group: 23.3% vs 8.3% respectively, albeit in the majority of the cases they were not considered to be so severe as to cause the interruption of the study. There were no clinically important changes from baseline in laboratory tests performed during the study. Endoscopy of the upper G-I tract was performed both at baseline and after 8 weeks of therapy in 30 patients per treatment group in order to obtain a reliable comparative evaluation of the G-I safety of the two drugs. Both drugs were found to be well tolerated; only 2 ulcers were observed after therapy in both groups, but minor lesions were more frequently detected in the mucosa of the stomach in the patients who received tenoxicam. The cumulative endoscopic index that reflected both the erosive and the haemorrhagic lesions found in the stomach taken as a whole was significantly (p < 0.03) higher after therapy in the tenoxicam group. These results indicate that 600 mg of etodolac SR u.i.d. for 8 weeks is as effective as 20 mg of tenoxicam u.i.d. in the treatment of OA of the knee and/or of the hip. Both the overall and the G-I specific safety profiles were found to be more favourable in patients treated with etodolac SR. Renal function was not substantially affected in either treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)