Search PubMed⌕ Search

Biomedical subjects

L Salvatore

Publications and source records attributed to L Salvatore.

At least 37 records · Page 2Linked to original sources

Vaccination of sheep against Fasciola hepatica with glutathione S-transferase. Identification and mapping of antibody epitopes on a three-dimensional model of the antigen.

The glutathione S-transferases (FhGST) of the liver fluke Fasciola hepatica have been identified as novel vaccine candidates that protect sheep against a fluke infection. With the use of overlapping peptides covering the predicted amino acid sequences of four FhGST cDNAs, we have defined the linear epitopes recognized by polyclonal antibody from sheep vaccinated with FhGST. Dominant and minor epitopes were found to be present on all four of the sequences although some epitopes were shown to be specific to particular FhGST. A high percentage of the FhGST peptides were found to be antigenic although considerable variability in response to the peptides was observed among the animals. This analysis was extended to the IgG1 and IgG2 response at the peptide level. Based on the recently solved crystal structure of the rat mu-class GST 3-3, a three-dimensional model of one of the FhGST sequences was generated that allowed the predicted spatial localization of defined epitopes. Most epitopes were localized on regions of high flexibility and accessibility. A comparison of epitopes on FhGST with the B cell epitopes on Sm28, a 28-kDa GST from Schistosoma mansoni, has found few similarities. There was no correlation between an antibody response to linear peptide epitopes and the level of protection induced in sheep by vaccination with FhGST.

Amino Acid Sequence↗

Vaccination of sheep with purified cysteine proteinases of Fasciola hepatica decreases worm fecundity.

There has been some evidence from several parasite systems that proteinases might have potential as protective antigens against parasitic infection. A cysteine proteinase complex identified in the regurgitant of adult F. hepatica was examined in this context. The thiol-cathepsin-related proteinases of M(r) 28,000 were purified and tested in vaccine trials of sheep infected with liver fluke. Ten animals were immunised with the purified proteinases and developed antibodies to the cysteine proteinases prior to challenge with F. hepatica metacercariae. Infection appeared to cause a boost in antibody response by Week 4 into infection, and antibody levels were generally sustained throughout infection. The cysteine proteinases are not novel antigens, since low-level antibody titres were also detected in nonimmunised controls by late infection. On completion of the trial, there was no difference in worm burden between the two groups. However, faecal egg counts and therefore worm fecundity were significantly decreased.

Animals↗

Neutrophil derived cathepsin G induces potentially thrombogenic changes in human endothelial cells: a scanning electron microscopy study in static and dynamic conditions.

Activated neutrophils may promote thrombus formation by releasing proteases which may activate platelets, impair the fibrinolytic balance and injure the endothelial monolayer. We have investigated the morphological correlates of damage induced by activated neutrophils on the vascular wall, in particular the vascular injury induced by released cathepsin G in both static and dynamic conditions. Human umbilical vein endothelial cells were studied both in a cell culture system and in a model of perfused umbilical veins. At scanning electron microscopy, progressive alterations of the cell monolayer resulted in cell contraction, disruption of the intercellular contacts, formation of gaps and cell detachment. Contraction was associated with shape change of the endothelial cells, that appeared star-like, while the underlying extracellular matrix, a potentially thrombogenic surface, was exposed. Comparable cellular response was observed in an "in vivo" model of perfused rat arterial segment. Interestingly, cathepsin G was active at lower concentrations in perfused vessels than in culture systems. Restoration of blood flow in the arterial segment previously damaged by cathepsin G caused adhesion and spreading of platelets on the surface of the exposed extracellular matrix. The subsequent deposition of a fibrin network among adherent platelets, could be at least partially ascribed to the inhibition by cathepsin G of the vascular fibrinolytic potential. This study supports the suggestion that the release of cathepsin G by activated neutrophils, f.i. during inflammation, may contribute to thrombus formation by inducing extensive vascular damage.

Animals↗

Prognostic value of the dipyridamole echocardiography test performed early after aortocoronary bypass surgery.

It has been demonstrated that high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography stress testing is feasible even in the first few hours after coronary artery bypass graft surgery and can be used to assess the beneficial physiological effects of coronary revascularization as well as graft patency. The aim of this study was to assess the role of dipyridamole echocardiography testing performed shortly after myocardial revascularization in the stratification of prognosis during follow-up. We studied 49 consecutive patients (45 males and 4 females; mean age 56 +/- 8 years) referred to our institute for elective myocardial revascularization. Six patients had single, 14 double, and 29 triple vessel disease. Forty-two left internal mammary artery grafts, 16 sequential venous grafts, and 45 single venous grafts were performed. All patients were submitted to dipyridamole echocardiography testing before (range 1-3 days) and shortly after (range 5-7 days) myocardial revascularization, always with the patients off antianginal medication. An arbitrary wall-motion score grading from 0 to 3 (normal, hypokinesia, akinesia, and dyskinesia) was applied to the seven regions into which the left ventricle was divided. Before surgery 48 patients showed wall-motion abnormalities during the test (47 patients also presented ECG changes). Angina occurred in 48 patients. One patient had ischemic ECG changes and angina. The mean wall-motion score was 3.11 per patient before and 6.5 per patient after the test (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Suitability of Doppler echocardiography for the assessment of right heart hemodynamics after De Vega tricuspid annuloplasty.

Cardiac Doppler Echocardiography is a suitable method for to evaluating right heart hemodynamics. However, the surgical correction of tricuspid valve annuloplasty changes valve geometry and might possibly lead to a technical obstacle to this estimation. The accuracy of Doppler echocardiography in the assessment of tricuspid regurgitation and systolic pulmonary pressure in patients who had undergone De Vega annuloplasty was evaluated in this study. Ten patients (9 females and 1 male), mean age 55.7 +/- 7.8 years, who had a previous De Vega annuloplasty for the treatment of tricuspid regurgitation due to a severe mitral stenosis, underwent a Doppler echocardiography study and, within two hours, right heart catheterization for a direct comparison of parameters calculated by different methods. Right ventricular-atrial maximal pressure gradient was found to be 32.6 +/- 11.07 mmHg by Doppler and 31.4 +/- 11.07 mmHg by catheterization. Pulmonary systolic pressure was 42.6 +/- 9.1 mmHg at Doppler and 39.1 +/- 11.3 mmHg at catheterization, with a highly significant correlation between the 2 techniques (r = 0.98%, p < 0.01). With semiquantitative Doppler evaluation 10 patients showed tricuspid insufficiency, which was mild in 8 and medium in 2. At catheterization all patients were found to have mild tricuspid insufficiency. Cardiac Doppler seems a reliable method in the evaluation of tricuspid regurgitation and of pulmonary systolic pressure even in patients who underwent De Vega annuloplasty.

Blood Pressure↗

Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica.

Glutathione S-transferases (GSTs) from Fasciola hepatica have been purified by glutathione affinity chromatography. Two closely migrating species of Mr 26,000 and 26,500 were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and several species resolved by two-dimensional gel analysis, indicating substantial heterogeneity among the GSTs. N-terminal amino acid sequencing revealed one core sequence containing three polymorphisms, whereas the sequence of GST peptides implied a minimum of three different GSTs. The amino acid sequence data assigned the F. hepatica GSTs to the mu class of GSTs with high similarities to these proteins in other helminths and mammals. The native GSTs of F. hepatica appeared to behave as dimers as determined by molecular sieving chromatography. The observation that the GSTs of F. hepatica are heterogeneous in sequence and behave as dimers in the native state suggest that these isoenzymes may exhibit considerable functional heterogeneity which may be of importance to the parasite. Immunocytochemical studies suggest that the main source of GST in F. hepatica are the parenchymal cells and peripheral tissues of the parasite. Some extracellular GST is associated with the lamellae of the intestinal epithelium. The identification of an intestinal GST is unique among trematodes studied to date.

Amino Acid Sequence↗

Myocardial vitamin E is consumed during cardiopulmonary bypass: indirect evidence of free radical generation in human ischemic heart.

Although a role for free radicals in myocardial damage during cardiopulmonary bypass for open heart surgery has been postulated, direct evidence of free radical production as well as consumption of tissue antioxidants such as vitamin E is still lacking. Twenty patients (age 26-66 yr, mean 48) undergoing elective open heart surgery with moderate hypothermia, and cold crystalloid cardioplegia, were studied. Cardiopulmonary bypass time was 61.4 +/- 31.2 min. The specimens of atrial tissue collection before and after cardiopulmonary bypass, were immediately frozen in liquid nitrogen. Mean vitamin E atrial content, measured by reverse phase HPLC, was 355 +/- 249 pmol/mg of dry weight basally, 135 +/- 85 pmol/mg (p < 0.05) at the end of the ischemic period and 405 +/- 288 pmol/mg after the reperfusion period (p < 0.01). Microscopic examination of right atrial biopsies ruled out differences in fibrosis or cellular damage as the cause of vitamin E changes. Although a great basal variability in atrial vitamin E content was observed, which was independent of age, sex and clinical status, a reproducible and substantial decrease in atrial vitamin E content after cardiopulmonary bypass occurred (mean reduction 45 +/- 17% and 55 +/- 22%, respectively, after ischemia and after reperfusion). This was directly related to the aorta cross-clamping duration and partially to the minimum temperature achieved. In conclusion, apart from the great variability observed in basal vitamin E tissue content, vitamin E was always reduced during cardiopulmonary bypass, suggesting an oxidative stress on the myocardium during open heart surgery.

Adult↗

[Destructive endocarditis caused by Streptococcus sanguis on normal valves after gastroduodenoscopy].

In recent years, epidemiological and clinical patterns in infective endocarditis are changed: mean age of patients, sex, underlying cardiac diseases, source of bacteremia, availability of better diagnostic methods--specially two-dimensional and doppler echocardiography--and surgical options. The Authors report a paradigmatic case of a young man without cardiac disease, who developed a destructive endocarditis complicated by refractory congestive heart failure; the cause was an organism of low pathogenicity, Streptococcus sanguis, that entered the bloodstream after gastroduodenoscopy.

Adult↗

Role of dipyridamole-echocardiography test in the evaluation of coronary reserve after coronary artery bypass grafting.

The object of this study was to assess the usefulness of the dipyridamole-echocardiography test in the early evaluation of coronary artery bypass grafting, when the use of an exercise stress test is precluded. We studied 39 consecutive patients (37 men and two women, mean age 57.3 years) referred to our institute for elective coronary artery bypass. Five patients had single, 12 patients double, 20 patients triple vessel disease, and two had left main stem disease. Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single vein grafts were performed. All the patients were subjected to the test before (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4 minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2 minutes (high dose) was given. During the test, blood pressure and a twelve-lead electrocardiogram were monitored. An arbitrary wall motion score was derived by dividing the left ventricle into six regions and grading from 0 to 3-normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the test was positive in 38 patients as evidenced by wall motion abnormalities (36 patients had electrocardiographic changes) and in one patient by electrocardiographic changes and chest pain; 22 tests were positive after the low dose and 17 after the high dose. Angina was present in 33 patients. Mean wall motion score was 1.64 per patient in the basal condition and 4.03 per patient after the test (p less than 0.001). After coronary bypass in three patients the test was positive at the same dosage that was used preoperatively, as shown by wall motion abnormalities (in two patients by electrocardiographic changes, as well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a treadmill stress test performed in these three patients was positive for ischemia and angina. The wall motion score was 1.25 per patient in the basal condition and 1.53 per patient after the test (no significant difference). When the preoperative wall motion score obtained after dipyridamole echocardiography was compared with the postoperative score, a statistically significant difference was seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight patients we observed an improvement of basal myocardial contractility after the operation, which indicates the reversibility of wall motion abnormalities observed before coronary bypass. In conclusion our data show that the dipyridamole-echocardiography test is a suitable method for the early assessment of bypass grafting when other methods, exercise dependent, are not indicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗

In vivo identification of mitral valve fibrosis and calcium by real-time quantitative ultrasonic analysis.

Conventional echocardiography provides fundamental information about mitral valve morphology and function but has a relatively low specificity in evaluating valve calcific deposits, which is critical information for the preoperative decision to perform commisurotomy or replacement. In vitro radiofrequency ultrasonic quantitative analysis of the mitral valve has been demonstrated to be a reliable tool in identifying normal, fibrotic and calcific valves. This study evaluates quantitative ultrasound characterization of the mitral valve in vivo. Thirty-three patients, scheduled to undergo mitral valve replacement, and 20 normal subjects (10 young and 10 older control subjects) were studied with a 2.25-MHz transducer. Radiofrequency signal was analyzed by a microprocessor system (used with an M-mode commercially available echocardiograph) for on-line evaluation of ultrasonic backscatter with 8 bits of amplitude resolution, 40-MHz sampling rate and a 1-microsecond acquisition gate. The integrated value of the rectified radiofrequency signal amplitude was deemed the integrated backscatter index. The highest value recorded with the ultrasonic analysis from each valve was taken as representative and expressed as the percent value with respect to the pericardial integrated backscatter index value of that subject. The 33 excised mitral valves underwent histologic examination. Four groups were identified: young controls (group I, n = 10); older controls age-matched with patients (group II, n = 10); patients with fibrotic mitral valves (group III, n = 13); and patients with calcific mitral valves (group IV, n = 20).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcinosis↗

Early assessment of coronary reserve after bypass surgery by dipyridamole transesophageal echocardiographic stress test.

The evaluation of coronary reserve within a few hours of aortocoronary bypass surgery could be of extreme utility for the follow-up or therapeutical management of these patients. In 11 men patients who underwent aortocoronary bypass surgery, a dipyridamole echocardiography stress test was carried out before (1 to 3 days), early after (68 to 130 minutes), and 1 week after surgery. The first and third tests were performed using a standard transthoracic approach, while the second was performed by a transesophageal approach. Dipyridamole was administered intravenously at a dose of 0.56 mg/kg body weight (low dose) and eventually adding 0.28 mg/kg body weight (high dose), always in the absence of antiischemic therapy. An arbitrary wall motion score (0 = eukinesia; 1 = hypokinesia; 2 = akinesia; 3 = dyskinesia) was assigned to the seven different myocardial regions in which the left ventricle was divided in order to have a semiquantitative score. Under basal conditions wall motion score per patient in the three series of tests did not change significantly (1.6, 1.4, and 1.5, respectively), while the mean score during dipyridamole administration showed significant differences (3.6, 1.9, and 1.9, respectively), indicative of the results obtained by surgical repair. The test, positive in all patients before surgery, showed wall motion abnormalities and ischemic ECG changes in two patients immediately after surgery by the transesophageal approach. One patient who had a normal basal contraction pattern and an abnormal response after the test developed in the following days a perioperative myocardial infarction, while a second patient in the follow-up period developed low-level effort angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of in vivo morphological results of balloon mitral valvotomy.

Percutaneous valvotomy is now more often considered for the treatment of mitral stenosis in poor risk patients. The aim of this study was the evaluation of the morphological changes produced by a similar procedure on the mitral valves of nine nonconsecutive patients undergoing a mitral valve replacement because of calcific isolated or prevalent mitral stenosis. The mitral valve was dilated through the left atriotomy before the valve excision with the same balloon catheter used in the percutaneous procedure. The pathological condition of the valve had been studied before dilatation by means of doppler echocardiography, cardiac catheterization and a visual examination performed by the surgeon before insertion of the balloon. At that time, the orifice area was measured with a Hegar dilator. A new measurement was performed after one or two dilatations performed at a balloon pressure of 2.7 atm. After excision, the valve was examined, photographed and X-rays were taken for evaluation of valve calcification. The pre-dilatation mean mitral valve orifice area was 1.3 +/- 0.4 cm2 and after the procedure was 2.8 +/- 0.3 cm2. In only one patient did the orifice area, originally 2.4 cm2, not increase. There was only one fused and calcified commissure, the other was normal. Before dilatation, the two commissures were fused in 17/18 cases and in 9/18, calcified. After dilatation, 5/17 commissures were completely open (not all were calcified), 10/17 incompletely opened and 2/17 remained fused (one in the above-mentioned patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery.

Interest in the antithrombotic potential of diets enriched with fish oil-derived polyunsaturated fatty acids (omega-3 PUFAs) prompted us to examine how these fatty acids, when taken preoperatively, affect hemostasis, plasma lipid levels, and production of prostacyclin (PGI2) by vascular tissues in atherosclerotic patients undergoing coronary artery bypass graft surgery. Fifteen patients with angiographically proven coronary artery disease received 3 g/day eicosapentaenoic acid and 1.3 g/day docosahexaenoic acid as capsules of purified fish oil for 28 days before surgery. Platelet aggregation induced by low concentrations of ADP, collagen, and epinephrine decreased (p less than 0.05) and serum thromboxane B2 decreased 36% (p less than 0.01) from baseline values. Bleeding times increased 40% (p less than 0.01) from baseline. Serum triglycerides decreased 50% (p less than 0.05) without a change in total serum cholesterol. Spontaneous production of PGI2 measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), its stable hydrolytic product, by saphenous vein and aortic and atrial tissues obtained at surgery was greater in tissues from patients receiving omega-3 PUFA supplements than in tissues from matched controls (13.8 +/- 2.2 versus 8.6, 21.0 +/- 3.1 versus 11.5 +/- 2.1, and 166 +/- 13 versus 102 +/- 15 ng/g, respectively, all p less than 0.05). Arachidonate-stimulated production of PGI2, as indicated by increased levels of 6-keto-PGF1 alpha, was increased. Despite changes in platelet function, bleeding time, and vascular PGI2, the perioperative blood loss was not increased in subjects receiving fish oil supplements. Thus, omega-3 PUFAs at moderate dosages may exert antithrombotic effects by increasing prostacyclin production by vessel walls as well as by direct inhibition of platelet activity.

Aged↗

In vitro identification of different degrees of mitral valve disease by online evaluation of radiofrequency ultrasound signal.

Sixty five mitral valves were studied in vitro with a 2.25 MHz transducer. Radiofrequency signals were analysed by a microprocessor system (implemented on an M-mode commercially available echocardiography) for online evaluation of ultrasonic backscatter (8 bits of amplitude resolution, 40 MHz sampling rate, 1 microsecond acquisition gate). The integrated value of the rectified signal amplitude was expressed as the integrated backscatter index (in db). The highest value recorded with ultrasonic scanning of each sample was taken as representative of that specimen. Calcification of mitral valves was assessed by radiography (24 mitral valves). Non-calcified mitral calves underwent pathological examination, and fibrotic valves (22 mitral valves) were differentiated from normal valves (19 mitral valves). A statistically significant (p less than 0.005) difference was recorded among the three groups for the index maximal value: calcific -7.4(3.1) db (mean(SD)), fibrotic -18.9(4.9) db, and normal -37.9(7.6) db. In conclusion, a microprocessor based system for online evaluation of radiofrequency ultrasonic signals, which may also be feasible for in vivo studies, provided a clear differentiation in vitro of calcific, fibrotic, and normal mitral valves.

Calcinosis↗

[Ambulatory ECG in the peroperative period].

The clinical recognition of perioperative myocardial necrosis represents one of the clue factors in the management of cardiac surgical patients (pts). This study was performed to determine whether there is any relationship between reperfusion ventricular fibrillation and/or ST-segment elevation and postoperative enzymatic release. Serum enzyme levels and ECG were monitored during and after cardiac operations in 23 pts (15 for valvular replacement and 8 for aortocoronary bypass graft). After aortic unclamping only 6 pts showed stable rhythm. Of the 17 pts who developed ventricular fibrillation 10 showed ST-segment elevation (83% of the 12 pts with ST-segment elevation). Although no significant difference was observed, pts with ST-segment elevation showed higher average enzyme (CK, CKMB) levels. Pts who had valvular replacement showed significantly higher serum CK and CKMB levels. Of the 4 pts who showed a second enzymatic peak, one died and another one presented complex ventricular arrhythmias. No correlation was observed between electrocardiographic data and post-operative enzymatic release. New theories concerning oxygen free radical generation during and after cardiopulmonary by-pass, with the related therapeutic perspectives, are discussed.

Cardiac Surgical Procedures↗

Cardiac damage due to nonpenetrating trauma. Report of four cases.

Four examples of cardiac damage secondary to nonpenetrating trauma in road accidents are described. Two patients had interventricular septal defect and other two had tricuspid insufficiency. In all four cases the lesion was not recognized at the time of the accident but became clinically important later. The time interval between trauma and surgery was one month to thirteen years. After surgical treatment, all four patients have continued to be asymptomatic.

Accidents, Traffic↗