Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in early diagnosis of sepsis.

Quantitation of neutrophil CD64 expression and procalcitonin (PCT) levels in blood samples have been recently proposed as useful tools for early detection of sepsis. To determine the usefulness of these tests, we analyzed blood samples of 112 patients, admitted to an intensive care unit (ICU), presenting clinical symptoms of sepsis, as well as of 50 healthy controls. At the end of the study, a retrospective analysis showed that only 52 of the 112 ICU-patients presented a real sepsis (positive blood culture). The results obtained indicated that of the 52 patients with sepsis, 50 and 49 presented levels of neutrophil CD64 expression >or= 2398 molecules per cell (cut-off determined by receiver operator characteristic analysis) and PCT levels >0.5 ng/ml (cut-off suggested by the manufacturer), respectively. However, the neutrophil CD64 test showed higher specificity in detecting sepsis since 5 out of the 60 ICU-patients without sepsis (negative blood culture), presented CD64 expression levels >or= 2398 molecules per cell, PCT levels >or= 0.5 ng/ml were shown in 27 patients. Moreover, while none of the 50 healthy controls presented a neutrophil CD64 level higher than the cut-off value, 5 patients presented PCT levels >or= 0.5 ng/ml. In conclusion, our data seem to indicate that the quantitation of CD64 expression could be taken into consideration as a sensitive and specific test for early diagnosis of sepsis.

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

Correlation between clinical and morphologic findings in unstable angina.

This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and intravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.

Comparison of coronary lesions obtained by directional coronary atherectomy in unstable angina, stable angina, and restenosis after either atherectomy or angioplasty.

The present study investigated the incidence of the histopathologic lesions and of growth factor expression in a consecutive series of directional coronary atherectomy (DCA) samples from 40 unstable angina pectoris patients without prior acute myocardial infarction and compared the findings with those obtained in DCA samples from 18 patients with stable angina without previous infarction and 18 patients with restenosis. We investigated coronary thrombosis, neointimal hyperplasia, and inflammation. For unstable angina, we correlated the angiographic Ambrose plaque subtypes with the histopathologic findings. The immunophenotype of plaque cells and the growth factor expression were assessed with specific antibodies for cell characterization and for the expression of basic fibroblast and platelet-derived AA and AB growth factors and receptors. The incidence of coronary thrombosis was 35% in patients with unstable angina, 17% in those with stable angina, and 11% in patients with restenosis. Neointimal hyperplasia was found in 38% of unstable angina cases, in 17% of stable angina cases, and in 83% of restenosis cases. Inflammation without thrombus or accelerated progression occurred in 20% of unstable angina and 6% of stable angina samples. In 52% of unstable angina cases, inflammation coexisted with thrombosis and/or neointimal hyperplasia. In the unstable angina group, 71% of the plaques with thrombus had a corresponding angiographic pattern of complicated lesions. The growth factor expression, reported as percentage of cells immunostaining with different growth factor antibodies, was highest in restenosis, followed by unstable angina and stable angina lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

[The evolution of the therapeutic choice in patients with the outcomes of non-Q myocardial infarct: 2 periods compared]. / Evoluzione della scelta terapeutica nei pazienti con esiti di infarto miocardico non-Q: due periodi a confronto.

BACKGROUND: Over the last years there has been a tremendous increase in coronary angioplasty procedures (PTCA), due to the availability of better materials and to the refinement of operators skill. It is not known however if this "PTCA boom" has modified our approach to the patients with particular clinical situations, such as those with non-Q wave myocardial infarction. The purpose of this study was to verify, in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction, the clinical decision concerning the therapeutical choice in two different periods (101 patients in 1988 vs. 102 patients in 1992). METHODS AND RESULTS: Patients in the two groups had similar clinical manifestations whereas patients observed in 1992 had more frequently 2-vessel disease than single vessel disease as compared to patients studied in 1988 (p < 0.05). The distribution of patients with normal coronary arteries or with 3-vessel disease was similar in the two periods. In 1988 medical therapy was the most recommended treatment at discharge (47%), followed by aorto-coronary bypass (29%) and coronary angioplasty (24%). On the contrary, in 1992 PTCA was performed in 48% of patients, medical therapy was recommended in 28% while the incidence of coronary surgery was reduced to 24% (p < 0.01). From a clinical point of view a significant increase in PTCA procedures was seen in patients presenting with unstable angina after the non-Q wave myocardial infarction (54% of these patients undergoing PTCA in 1992 vs. 30% in 1988, p = 0.03) and in patients with effort angina and a positive exercise test at low workload (53% of these patients undergoing PTCA in 1992 vs. 22% in 1988, p < 0.05). Moreover, in 1992 PTCA procedures increased in patients with single vessel disease (64% in 1992 vs. 49% in 1988) and in patients with 2-vessel disease (64% in 1992 vs. 9% in 1988). Therefore, in these patients the need of aorto-coronary by pass was reduced from 39% in 1988 to 19% in 1992 (p < 0.05). The success rate of PTCA procedures was 98% in 1992 and 83% in 1988. No major complications were observed in the two study periods and no patients underwent urgent coronary surgery. CONCLUSIONS: These data show an increase in PTCA procedures over the last years in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction. The greater experience of operators allowed for improved results, thus reducing the need of coronary surgery in these patients.

Folate status in Italian blood donors: relation to gender and smoking.

BACKGROUND AND OBJECTIVES: Folate deficiency in the general population is associated with a risk of cardiovascular disease and various cancers. The aim of this study was to evaluate folate status in Italian blood donors and its relationship with gender and smoking habit. DESIGN AND METHODS: A prospective study of 201 first visit donors (99 males and 102 females) was undertaken to evaluate folate status by measuring serum folate (SF) and red blood cell folate (RCF) levels and relating those with gender and smoking habit (100 smokers and 101 non-smokers). RESULTS: The rates of SF level less than 6.8 nmol/L and RCF less than 340 nmol/L were 9.9% and 25.3%, respectively in Italian blood donors. Mean RCF level was significantly lower (p<0.05) in females than in males and in smokers compared to non-smokers (p<0.001). The risk of reduced RCF levels in smokers was related to the number of cigarettes smoked per day, more than nine cigarettes increased the relative risk (RR) of low RCF level to 2.93 (95% C.I.: 1.34-6.41). INTERPRETATION AND CONCLUSIONS: This study suggests that folate deficiency, evaluated by RCF and SF levels, is widespread in Italian blood donors. Moreover, RCF values seem related to gender in non-smokers and modified by smoking habit, according to the cigarettes number smoked per day.

Influence of plaque morphology on the mechanism of luminal enlargement after directional coronary atherectomy and balloon angioplasty.

OBJECTIVE: To relate the mechanism of luminal gain after directional atherectomy and balloon angioplasty to the morphological characteristics of the coronary lesions, assessed by intravascular ultrasound imaging. DESIGN: Intravascular ultrasound imaging was performed before and after the revascularisation procedure to assess the contribution of wall stretching and plaque reduction in luminal gain. SUBJECTS: 32 patients undergoing balloon angioplasty and 29 undergoing directional coronary atherectomy. MAIN RESULTS: The main luminal area in vessels treated by balloon angioplasty increased from 1.51 (SD 0.30) to 3.91 (1.09) mm2 (P < 0.0001) with a concomitant increase in total vessel area from 11.44 (2.73) to 13.07 (2.83) mm2 (P < 0.0001). Therefore stretching of the vessel wall accounted for 68% of the luminal gain while plaque reduction accounted for the remaining 32%. This mechanism ranged from 45% in non-calcific plaques to 81% in echogenic plaques. The main luminal area in vessels treated by directional atherectomy increased from 1.49 (0.32) to 4.68 (1.73) mm2 (P < 0.0001), with a concomitant increase of total vessel area from 13.61 (4.67) to 15.2 (4.04) mm2 (P = 0.006). Thus stretching of the vessel wall accounted for 49% of the luminal area gain and plaque reduction for the remaining 51%. The presence of calcium influenced the relative contribution of these two mechanisms to the final luminal gain after directional atherectomy, since in calcific plaques stretching of the vessel wall accounted for only 9% of the luminal gain as compared to 56% in non-calcific plaques. After balloon angioplasty there was greater evidence of coronary dissections (32% v 3% after directional atherectomy, P < 0.01) and plaque fissure (60% v 0%, P < 0.01). Plaque fissure was more frequently seen in echolucent and concentric lesions, whereas dissections prevailed in echogenic and eccentric lesions. CONCLUSIONS: Intravascular ultrasound imaging may allow the assessment of acute changes in lumen and vessel wall after revascularisation procedures, and help in evaluating the potential effect of the structure and morphology of coronary lesions on the mechanism of luminal enlargement.

[Diagnostic and research potential of directional atherectomy]. / Potenzialità diagnostica e di ricerca dell'aterectomia direzionale.

Directional coronary atherectomy (DCA) is the sole technique for the in vivo study of coronary artery plaques which are responsible for myocardial ischemia. The technique confers the following advantages to the pathologic study of plaque samples: the brevity, in general, of the interval between acute myocardial ischemia and sampling of the guilty plaque; the absence in samples of autolytic phenomena (such as those that affect autopsy samples), an effect that enables the use of conventional histopathology, immunohistochemistry and molecular biology; the certainty with which the researcher can identify, and thus sample, the truly guilty lesions. The drawbacks of the technique are: the fragmentation of the plaque; the difficulty the pathologist has in correctly orientating the samples in the embedding phase, in distinguishing pre- from post-procedural lesions, and in providing a detailed description of the findings. Given the foregoing, the diagnostic information to which DCA sampling enables access is as follows: plaque derivation--the recognition of whether tissue removed with DCA originates from eccentric or concentric, atheromatous of fibrosclerotic, calcified or not calcified plaques; histopathology of coronary lesions that cause ischemia with regard to: evidence of acute events, such as thrombosis, ulceration and hemorrhage, thrombus composition, when it occurs, and definition of its age and presence of material deriving from the vascular wall that lies beyond the plaque; identification and immunophenotypical characterization of inflammatory infiltrates. As regards research, the main implications of DCA are for the study of the pathogenetic mechanisms that lead to plaque instability in acute ischemic syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group]. / Reperti histopatologici [corrected] in campioni di aterectomia ottenuti da pazienti con angina instabile, con angina stabile e con ristenosi. Gruppo Lombardo Aterectomia Direzionale, GLAD.

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.