Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

OBJECTIVES: Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. DESIGN: Longitudinal clinical study. SETTING: Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. PARTICIPANTS: The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. MEASUREMENTS: Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. RESULTS: A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. CONCLUSIONS: Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of 'bridging' antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel.

BACKGROUND: Patients with a recently implanted coronary drug-eluting stent (DES) who need urgent surgery are at increased risk of surgical bleeding unless clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been associated with a high rate of adverse events due to stent thrombosis. This pilot study tested the hypothesis that the i.v. perioperative administration of the short-acting antiplatelet agent tirofiban allows the safe withdrawal of clopidogrel without increasing the rate of surgical bleeding. METHODS: Phase II study with a Simon two-stage design. RESULTS: Thirty patients with a recently implanted DES [median (range) 4 (1-12) months] and high-risk characteristics for stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was to be withdrawn 5 days before surgery, and tirofiban started 24 h later, continued until 4 h before surgery, and resumed 2 h after surgery until oral clopidogrel was resumed. The use of aspirin was decided by the surgeon. There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0-11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding. CONCLUSIONS: In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a 'bridging strategy' using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding.

Serum sFas/sFasL ratio in systemic lupus erythematosus (SLE) is a function of age.

Fas and Fas ligand (FasL), members of the tumor necrosis factor (TNF) and TNF-receptor (TNFR) families of molecules, are involved in apoptosis. They are expressed in membrane-associated as well as soluble forms (sFas, and sFasL). Apoptotic defects underlie some models of autoimmune diseases, and they have been proposed in the pathogenesis of systemic lupus erythematosus (SLE) a prototypic autoimmune disorder. We measured the serum levels of sFas and sFasL in a series of well characterized SLE patients and devised an index of the two forms which resulted to be associated with age, indicating that apoptosis resistance is modulated during aging, thus explaining the conflicting observations made in previous studies.

Complete or incomplete percutaneous coronary revascularization in patients with unstable angina in stent era: Are early and one-year results different?

The aim of our study was to evaluate the impact of a strategy of incomplete revascularization by PTCA, with or without stent implantation, on clinical outcome of 208 consecutive patients (171 men) with unstable angina and multivessel coronary artery disease. Mean age of the group was 63.8 +/- 10.3 years (range, 31-91). Complete and incomplete revascularization was achieved in 49 and 159 patients, respectively. A total of 226 stents were implanted in 172 patients (1.31 +/- 0.65 stent per patient), equally distributed between the two groups. Left ventricular ejection fraction < 40% and total chronic coronary occlusions were significantly more frequent in patients with incomplete revascularization than in those with complete (P = 0.014 and 0.001, respectively). In-hospital MACE occurred in 10% and 7.5% of patients with complete and incomplete revascularization, respectively (P = NS). By multivariate analysis, multiple stent implantation (OR, 5.44; 95% CI, 1.21-24.3), presence of thrombus in the treated lesion (OR, 6.3; 95% CI, 1.53-25.9), Braunwald class III (OR, 4.74; 95% CI, 1.08-20.8), and ad hoc PTCA (OR 4.51; 95% CI, 1.11-18.3) were significantly related to in-hospital outcome. At 1-year follow-up, 11.3% and 11.5% of patients with complete and incomplete revascularization, respectively, had MACE. In all patients, diabetes (OR, 3.40; 95% CI, 1.09-10.58) and presence of thrombus in the treated lesion (OR, 3.48; 95% CI, 1.12-10.84) were significant predictors of 1-year outcome by multivariate analysis. These results indicate that the strategy of incomplete revascularization in unstable angina patients with multivessel coronary disease does not expose them to a higher risk of death or other major ischemic events in comparison to those undergoing complete revascularization.

[Percutaneous radial approach for coronary angiography]. / Approccio radiale percutaneo per angiografia coronarica.

BACKGROUND: The Sones technique for coronary angiography has been abandoned by most of laboratories. Nevertheless, in some circumstances (anticoagulation, peripheral arteriopathy, outpatients procedures), the femoral entry site may be troublesome. We evaluated the feasibility and safety of percutaneous transradial approach to coronary angiography as an alternative way to the usual femoral approach. METHODS: Since July to october 1995 we performed 200 consecutive coronary angiographies via radial artery with percutaneous approach. Exclusion criteria were the absence of radial pulse, abnormal Allen test and the need to perform right catheterism. No patient was excluded because of age or other clinical reason. We used right radial artery in 192 cases, left radial artery in 7 cases and both right and left artery in 7 cases. Thirteen patients (6.5%) had previous CABG. Thirteen patients were under treatment with heparin or dicoumarol. Twenty-one patients (10.5%) were affected by lower extremities arteriopathy. Five patients had previous coronary angiography by Sones technique. Fifty-eight patients (29%) underwent coronary angiography on outpatient basis. We used 6 F catheters in all cases but one. 5000 UI heparin bolus was injected in all cases. Sheaths were pull-out immediately after the procedure. We used Judkins L 3.5 and Judkins R 4 as first choice catheter. RESULTS: We succeeded in performing a complete coronary angiography in 189 patients (94.5%). In 11 patients the angiography had to be performed or completed by femoral approach: we failed in radial artery puncture in 5 patients; in 2 patients the guidewire could not be advanced beyond brachial bifurcation; in 1 very tall patient the catheter distal extremity did not reach coronary ostia; in 1 case were not able to do selective injection in left coronary ostium because of brachiocephalic trunk tortuosity; in 2 patients resistant radial artery spasm occurred. It was necessary to change the first choice catheter in 17 patients (8.5%) for left coronary artery and in 4 patients (2%) for right coronary artery. Clinical complications were ventricular fibrillation in 1 case and vasovagal reaction in 3 cases. Local complications were mild haematic effusion in 5 cases, small haematomas in 2 cases. In 12 patients radial artery pulsations were not palpable at discharge; in 4 of them radial artery pulse spontaneously reappeared after a week. CONCLUSIONS: Percutaneous transradial approach for coronary angiography is safe and feasible and represents a good alternative entry method mainly in patients with peripheral arteriopathy, in patients treated with anticoagulants and in outpatients coronary angiography.

[Thallium-dipyridamole in acute myocardial infarction treated by thrombolysis: diagnostic and prognostic value]. / Il tallio-dipiridamolo nell'IMA non complicato trattato con trombolisi: valore diagnostico e prognostico.

BACKGROUND: The management of patients who received thrombolytic therapy for acute myocardial infarction is still controversial. It is not clear if the strategies usually followed after myocardial infarction for risk stratification have the same value when applied to patients treated with thrombolysis. METHODS: To assess the diagnostic and prognostic value of dipyridamole thallium-201 scintigraphy in the "thrombolytic era", we studied 110 consecutive patients younger than 75 recovering from first uncomplicated acute myocardial infarction treated with thrombolytic agents. Patients with early angina, recurrent acute myocardial infarction, heart failure, life-threatening arrhythmias, non Q wave myocardial infarction were excluded. Ninety patients were treated with streptokinase, 14 with rtPA, 6 with APSAC: All patients underwent dipyridamole thallium scintigraphy with standard dose and coronary angiography before discharge (10-20 days). Ninety-nine patients underwent exercise test. All patients were followed-up for 22 +/- 9 months (range 8-42). Perfusion abnormalities were classified as reversible (totally or partially) defects or persistent defects and within or outside the infarct zone. RESULTS: Fifty-eight patients developed anterior and 52 inferior acute myocardial infarction. Coronary angiography showed single vessel coronary artery disease in 66 patients, multivessel disease in 34, and normal coronary arteries or sub-critical stenosis in 10. No major complications (death, myocardial infarction, threatening arrhythmias, prolonged severe hypotension) occurred after dipyridamole infusion. Sixty-two patients had reversible perfusion defects at thallium scanning (34 within the infarct zone, 21 within and outside the infarct zone, 7 outside); 38 patients had persistent defects; 10 patients had a normal scintigraphic pattern. The diagnostic value of homozonal perfusion reversible defects for identifying a patent infarct-related vessel was poor (sensitivity 69.7%, specificity 64.7%). The diagnostic values of the same scintigraphic pattern improved in detecting patent infarct-related artery with residual critical stenosis (sensibility 75.4%, specificity 77.3%); in all the false positive cases (reversible defects within the infarct zone and occluded infarct-related artery) a good collateral flow was present. The sensitivity of reversible defects outside the infarct zone in detecting multivessel disease was 64.7% vs 56.3% of exercise test; the specificity was 92% vs 64%; the positive predictive value 78.6% vs 44%; the negative predictive value 85.3% vs 74.5%; the diagnostic accuracy 83.6% vs 61.4%. During the follow-up 2 deaths, 7 recurrent myocardial infarction, 1 sustained ventricular tachycardia, 1 heart failure, 13 recurrence of unstable angina and 9 revascularization procedures occurred among patients with reversible defects (either within or outside the infarct zone) at thallium scanning. One recurrent myocardial infarction, 4 recurrence of unstable angina and 2 revascularization procedures were the events among patients with persistent defects or normal scintigraphic pattern (p < 0.001). Ischemic events occurred with similar frequency in patients with reversible perfusion defects within the outside the infarct zone (55% vs 50%, NS). CONCLUSIONS: Dipyridamole thallium-201 scintigraphy performed after uncomplicated myocardial infarction treated with thrombolytic agents is a valuable diagnostic tool in identifying viable jeopardized myocardium within the infarct zone perfused by a patent but critically narrowed vessel; it shows better diagnostic accuracy in detecting multivessel disease than does the exercise test and is able to identify a subset of patients at risk for future ischemic events after thrombolytic therapy.

Sonography after renal biopsy: assessment of its role in 230 consecutive cases.

Among 230 patients undergoing ultrasound (US) guided renal biopsy, 218 had postbiopsy sonography. Clinical records were reviewed to correlate symptoms to US findings. In each case of large hematoma (thickness above 1 cm), all postbiopsy sonographic studies were analyzed to look for findings indicative of unfavorable outcome. A total of 96 subcapsular/perirenal hematomas were found. Large hematomas were observed in 20 patients (20/230 = 8.7%), seven of these (3%) were severely symptomatic. In the absence of clinical signs of bleeding, no patient had clinical consequences. In the presence of clinical signs of bleeding, serious complications occurred only in patients with large hematomas. US thickness of retroperitoneal hematoma correlated to clinical outcome: whenever measured thickness was less than 2 cm, clinical evolution was very favorable, whereas a thickness above 2 cm was invariably associated to clinical signs of bleeding. In six of seven cases of thickness exceeding 3 cm, severe complications developed. An unfavorable evolution was associated with increasing thickness and an echogenicity inappropriate with respect to the time elapsed since biopsy. Hydroureteronephrosis, peritoneal effusion, and anomalous vascular images were indicators of deterioration. We conclude that sonography is indicated only for symptomatic patients and that the monitoring of both thickness and changing echogenicity of retroperitoneal blood collections supplements clinical follow-up.

Dipyridamole-echocardiography in coronary artery disease.

Regional wall motion impairment incurred by means of dipyridamole-induced ischemia, is regarded with higher sensitivity and specificity than the conventional findings in the ECG. Based on the latter considerations, a new test, the dipyridamole echocardiogram has been introduced in which the development of regional wall motion impairment is designated as the positive diagnostic criterion. Dipyridamole is a vasodilator of coronary arterioles. During the course of the examination, three consecutively occurring mechanisms are considered responsible for the appearance of dipyridamole-induced ischemia in the presence of coronary stenosis. The ischemia is initially attributed to a steal-effect, then to reflex-induced rise in rate-pressure product and, lastly, to a vasospastic component. In 680 patients with thoracic pain, on use of 0.84 mg/kg over ten minutes, there was a sensitivity of 74% in detection of angiographically-documented coronary artery disease, defined as greater than 70% stenosis in at least one major coronary artery, and a specificity of 95%. The onset of regional wall motion impairment after dipyridamole infusion was correlated with the severity of the disease, the localization of the wall motion impairment enabled delineation of the localization of the stenosis in the coronary vascular system. By means of the dipyridamole echocardiogram, the effectiveness of therapeutic measures such as PTCA, ACVB, medical antianginal treatment and thrombolysis can be assessed. Lastly, the dipyridamole echocardiogram provides important information with regard to prognosis.

[Prognostic stratification of non complicated acute myocardial infarct. Usefulness of the dipyridamole test with ecg-echo-thallium 201]. / Stratificazione prognostica dell'ima non complicato. Utilità del test al dipiridamolo con ecg-eco-tallio 201.

84 patients (pts) with recent first uncomplicated myocardial infarction underwent during the early post-infarction period, dipyridamole (D) test (EKG-ECHO-THALLIUM) and coronary arteriography in order to verify its feasibility, safety and usefulness in the detection of residual jeopardized but viable myocardium and in the diagnosis of multivessel disease. 69 pts performed a pre-discharge exercise test. During the execution of D test no major side effect occurred. The D-Echo was positive for residual ischemia in 41 pts (48.8%), the D-Thallium in 49 pts (58.3%) and the exercise test in 30 pts (43.5%). Both the imaging techniques allow the recognition of viable myocardium within the infarct zone (homozonal positivity) or outside the infarct zone (heterozonal positivity). The sensibility and specificity for multivessel disease are, respectively: with D-echo 50% and 100%; with D-thallium 60% and 100%; with exercise test 48% and 63%. D test has better diagnostic accuracy than exercise test in detecting multivessel disease; in particular we emphasized the excellent specificity of D-echo and D-thallium test. Poliparametric approach with D-test and exercise test gives a better stratification of the ischemic post-infarction risk.

[Left atrial myxoma: radioisotopic diagnosis]. / Mixoma atriale sinistro: diagnosi radioisotopica.

A case of left atrial Myxoma shown on an equilibrium radionuclide ventriculography is presented. The finding were consistent with the ecocardiographic patterns and the gross anatomy of the tumour. The analysis of various parameters obtained with gated radionuclide cardiac blood pool scan shows that the Fourier phase image is another method to detect and study this disease.

[Fixed subvalvular aortic stenosis. Monodimensional echocardiographic findings]. / Stenosi aortica sottovalvolare fissa. Reperti ecocardiografici monodimensionali.

19 patients affected by discrete subvalvular aortic stenosis were studied by M-mode echocardiography. The diagnosis was confirmed by cardiac catheterism and angiocardiography and by anatomic evidence in operative room. The most frequent echocardiographic pattern was the abnormal protosystolic movement of aortic valve leaflets, that was found in all the patients. A discrete linear echo in the outflow tract of the left ventricle was observed in almost half of the cases. In 40% of the cases the left ventricular outflow tract was narrowed. The relations between these echocardiographic patterns and the anatomical kinds of discrete subaortic stenosis are discussed. No correlations were found between echocardiographic patterns and severity of the subaortic stenosis.

[Dyslipidemia and coronary disease. Clinico-coronarographic study]. / Dislipidemia e coronaropatia. Studio clinico-coronarografico.

An inverse relationship between alpha-cholesterol and coronary atherosclerosis was observed in 200 male patients given coronographies. Specifically the lowest alpha-cholesterol levels were observed in patients with the most serious and widespread atherosclerotic lesions. This inverse correlation was maintained at the same level in all age groups.

[The natural development of arteriosclerotic coronary disease. Coronarographic study in time intervals]. / L'evoluzione naturale della coronaropatia aterosclerotica. Studio coronarografico seriato nel tempo.

In 96 patients with coronary artery disease a coronary arteriography was performed twice at least with some months' interval, in order to establish the rate of progression of coronary atherosclerosis and the factors which could affect this progression. It was possible to select patients with progression of the coronary arteria lesions from patients with no increase of coronary stenosis. From the angiographic point of view, the progression of angina and the appearance of myocardial infarction are connected with a general progression of arterial lesions on all main coronary branches. As to the electrocardiographic aspects, the ECG at rest give no informations about the evolution of the coronary disease. Among the risk factors the smoking only has some importance in order to predict the progression of the coronary atherosclerosis.

[Aortic valve disease and coronary atherosclerosis. Clinical and coronarographic study (author's transl)]. / Valvulopatia aortica e aterosclerosi coronarica.

77 patients with aortic valve disease have undergone heart catheterization in prevision of valve replacement: in this group the incidence of angina pectoris and the incidence of coronary artery disease associated with the valvular disease have been evaluated. The most important data resulting from out study are: 1) High frequency of angina pectoris both aortic stenosis and in aortic regurgitation: respectively about 60% and 50%. 2) The frequency of coronary atherosclerosis associated with aortic valve disease is much higher in aortic stenosis than in aortic regurgitation: respectively 35% versus 15%. 3) Coronary atherosclerosis associated with aortic stenosis frequently occurs (about 30%) also in young-aged patients (under 40 years). On the contrary in case of aortic regurgitation it occurs much more frequently in elderly patients. 4) The absence of angina both in aortic stenosis and in aortic regurgitation virtually excludes the presence of associated coronary atherosclerosis. 5) The presence of angina in aortic stenosis indicated either severe valvular stenosis or associated coronary artery disease (in this case the valvular stenosis is mild or moderate). The presence of angina in aortic regurgitation indicates either severe impairment of left ventricular performance or associated coronary atherosclerosis.