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Biomedical subjects

A Grossi

Publications and source records attributed to A Grossi.

At least 91 records · Page 5Linked to original sources

HPLC with o-phthalaldehyde precolumn derivatization to measure total, oxidized, and protein-bound glutathione in blood, plasma, and tissue.

This HPLC assay with o-phthalaldehyde precolumn derivatization is used to measure the total, oxidized, and protein-bound forms of glutathione in human blood, plasma, and rat tissue. Total glutathione (i.e., sum of reduced, oxidized, and protein-bound fractions) was determined after reduction with dithiothreitol and protein precipitation with perchloric acid (PCA). A preliminary selective blockage of free sulfhydryl groups with N-ethylmaleimide was necessary to evaluate the different oxidized forms. The assay showed high sensitivity (< 0.05 pmol injected) and good precision (within-day CVs of 5.5% to 6.4%), recovery (101% +/- 4%), and linearity (r > 0.999). Samples, after PCA acidification, were stable at room temperature and 4 degrees C for 3 days, and at -20 degrees C and -80 degrees C for > 1 month. The method (involving automated derivatization) not only is very rapid and simple but also allows immediate processing of many different biological samples.

Animals↗

[Blood preservation in thoracic surgery: feasibility and limitations].

The transfusion of homologous blood carries risks associated with reactions to transfusion and the transmission of diseases. Minimizing surgery-related blood use is therefore of utmost importance. However, the application of blood-saving methods in surgery is restricted by a number of factors. Thoracic surgery poses particular problems in this regard due to the type of diseases treated, patients' general status and the use of neoadjuvant chemotherapy protocols. The aim of this study was to analyse the feasibility of a blood conservation program for thoracic surgery. A detailed analysis of blood-sparing techniques was carried out and the factors influencing blood consumption were evaluated in the preoperative, intraoperative and postoperative periods. Although pre-operative autologus blood donation is an extremely important factor, its effect is limited in thoracic surgery since only a few patients are suitable candidates for such a procedure. Our personal experience confirms the difficulty of applying a blood sparing program to thoracic surgery. Nevertheless the risks associated to transfusions, especially those related to the use of homologous blood, can be reduced by optimizing existing blood sparing techniques or developing new hemostatic agents.

Blood Group Incompatibility↗

Surgery following neoadjuvant MPV chemotherapy (mitomycin, cisplatin, vinblastine) in locally advanced (IIIa and IIIb) non-small cell lung cancer.

From November 1990 to August 1993, 32 patients with non-small cell lung cancer (NSCLC) entered a multimodality treatment study with neoadjuvant Mitomycin, Cisplatin and Vinblastine (MPV), surgery and radiotherapy at the San Raffaele Hospital in Milan, Italy. Neoadjuvant chemotherapy was performed on an outpatient basis. To date 23 patients (11 stage IIIa and 12 stage IIIb) have completed the chemotherapy treatment and are available for evaluation of response, toxicity, surgical eligibility and resection rate. The overall major response to MPV chemotherapy was 87%. The overall resection rate after major response to treatment was 60% (90% in stage IIIa and 17% in stage IIIb). After a median follow-up of 21 months (8-31) 17 patients are still alive (74%). Ten patients (83%) who had a complete resection are alive after a median follow-up of 23 months (21-30) and eight of them (66%) are in complete pathological remission. No treatment-related mortality was observed. The authors conclude that MPV is a highly effective neoadjuvant regimen for NSCLC and is feasible on an outpatient basis. Favorable resection rates can be obtained in stage IIIa patients. Stage IIIb patients can be downstaged and undergo complete resection. A longer follow-up is needed to assess the impact of this multimodality approach on long-term survival and to evaluate the role of adjuvant radiotherapy.

Adult↗

Myocardial revascularization with bilateral internal thoracic artery in patients with left main disease: an incremental risk?

Although the long-term patency of the internal thoracic artery (ITA) has been well proved, there is still some concern about its preoperative performance. We considered 80 patients with left main disease (mean age 60.2 years) who underwent coronary artery bypass grafting in our institute from March 1988 to September 1992. Patients with left main disease were divided into 2 groups: group I-38 patients receiving only ITA grafts on the left coronary system and group II-42 patients having a single ITA graft together with saphenous vein grafts on the left coronary system. No patients in group I received a saphenous graft on the left coronary system and three patients with right coronary artery involvement received total arterial myocardial revascularization with the use of the inferior epigastric artery. Perioperative complications in group I and group II patients were, respectively: myocardial necrosis in 2 (6.9%) and 3 (8.8%), use of intraaortic balloon pump in 2 (6.9%) and 2 (5.9%). No death occurred in either group. In our experience, the use of bilateral ITA grafts in patients with left main stenosis was not related to an incremental risk. We conclude that left main disease should not be considered as counterindication to the extensive use of arterial conduits.

Aged↗

Identification and revascularization of hibernating myocardium in angina-free patients with left ventricular dysfunction.

We examined 17 angina-free patients with left ventricular dysfunction, referred for surgical decision-making, who presented with no or few signs and symptoms of myocardial ischemia according to treadmill stress test. On cardiac catheterization they were affected by severe multi-vessel coronary artery disease; the mean left end-diastolic pressure of this population was 26.3 +/- 5.5 mm Hg (mean +/- SD) and their mean ejection fraction was 27.6 +/- 4.9% (mean +/- SD). They all were investigated for the presence of viable myocardium by the combined assessment of cardiac perfusion and metabolism using single photon emission tomography with [99mTc] labelled hexakis-2-methoxy-isobutyl-isonitrile [99mTc]MIBI/SPET) and positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG/PET), respectively. Patients were considered for coronary surgery when [18F]FDG was detectable in at least two cardiac segments with wall motion abnormalities and perfusion defects. Nine patients were operated on, six were medically treated and two were scheduled for heart transplantation. We recorded no in-hospital mortality. At a mean follow-up of 28.4 +/- 9.8 (mean +/- SD) months all surgical patients were alive and their NYHA functional classes have improved, except in one case. Among the patients refused for bypass surgery, three are in stable conditions, three have worsened clinical statuses and two died while waiting for heart transplantation. In conclusion, for patients with bypassable coronaries, left ventricular dysfunction and lack of angina, successful coronary revascularization may be predicted by the presence of viable myocardium demonstrated with positron emission tomography.

Adult↗

Inhibition of erythropoietin production in vitro by human interferon gamma.

The effects of interferon-gamma (IFN-gamma), alone and in combination with IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), on in vitro erythropoietin (Epo) production by the human hepatoma Hep3B cell line were evaluated. The addition of IFN-gamma to either unstimulated or cobalt chloride (CoCl2)-treated Hep3B cells resulted in a dose-dependent inhibition of Epo release in the medium by as much as 70% at 1000 U/ml. Half-maximal inhibition was observed at around 50 U/ml. According to previous observations, IL-6 had a stimulatory effect on Epo production by CoCl2-treated Hep3B cells; however, the simultaneous addition of IFN-gamma and IL-6 resulted in a reversal of the stimulatory effects due to IL-6. IFN-gamma and IL-1 had an additive inhibitory effect, whereas IFN-gamma and TNF-alpha acted in a synergistic fashion in inhibiting Epo production by Hep3B cells. The inhibitory effect of IFN-gamma appeared to be due to a down-modulation of Epo mRNA levels in CoCl2-treated Hep3B cells, as shown by Northern blot analysis. These data indicate that Epo production by hepatoma cells in vitro is inhibited by IFN-gamma, and that a complex network of interacting cytokines may regulate Epo production in response to an hypoxic stimulus. Overall, these results also suggest that IFN-gamma might have a role in the defective Epo production observed in several inflammatory and immunemediated disorders characterized by relatively high IFN-gamma plasma levels.

Blotting, Northern↗

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO4. However, vitamin E efficiency was lower (9.6 +/- 4.2 versus 30.2 +/- 7.6 min/nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5 +/- 16.5 versus 58 +/- 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu(2+)-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Assisted circulation in postcardiotomy heart failure: experience with the Bio-Medicus centrifugal pump in ten patients.

Between January 1990 and September 1992, ten patients required assisted circulation for postcardiotomy heart failure which was unresponsive to inotropic drugs and aortic counterpulsation. All patients were supported by a Bio-Medicus centrifugal pump (biventricular assist in five, left ventricular in three, right ventricular in two); six had ischaemic heart disease, two a congenital ventricular septal defect, one an acute mitral valve incompetence and one an aortic type 'A' dissection. The mean duration of circulatory support was 5.1 days (range 2 hours to 8 days). Six patients were weaned from the device and four were discharged; the perioperative deaths among the patients weaned from support were the result of cerebral haemorrhage and multiorgan failure respectively. No late deaths occurred at a mean follow-up of 15 months. Common complications were bleeding (40%), acute renal failure (30%) and sepsis (30%). All patients who developed renal failure died. The high incidence of haemorrhagic complications makes the use of pre-heparinized circuits desirable as these patients do not then require additional anticoagulation.

Acute Kidney Injury↗

Measurement of cardiac troponin T and myosin to detect perioperative myocardial damage during coronary surgery.

This study evaluated the use of monitoring blood levels of the isoenzyme of creatine phosphokinase, troponin T (tnT) and myosin in the detection of perioperative myocardial damage after coronary artery surgery. Serial blood samples were collected in 24 patients undergoing myocardial revascularization. The patients were retrospectively divided into three groups: group A with no changes in their electrocardiogram; group B showing non-specific signs of perioperative myocardial infarction such as deep and permanent T wave inversion; and group C with definite electrocardiographic signs of perioperative myocardial infarction (new persistent Q-waves and loss of R-waves). Group A (n = 17) demonstrated a mean(s.d.) troponin T peak blood level of 0.64(0.35) ng/ml at 12-24 h after surgery, a myosin peak of 1030(670) mu units/l at 3-6 days afterwards, and a creatine phosphokinase isoenzyme peak of 25.8(10.6) units/l. In group B (n = 5), mean(s.d.) troponin T levels were elevated to a peak of 4.8(3.9) ng/ml 24 h after intervention, while myosin rose to 2074(340) mu units/l 3-6 days after surgery and creatine phosphokinase isoenzyme reached 57.8(38) units/l. Group C (n = 2) had a mean(s.d.) troponin T peak of 4.8(2.6) ng/ml, a myosin peak of 2404(392) mu unit/l and a creatine phosphokinase isoenzyme peak of 88.5(20) units/l. Peak values of troponin T and myosin in groups B and C were statistically different from those in group A (P < 0.001). These results suggest that troponin T and myosin are reliable indicators of perioperative myocardial damage. In particular, troponin T may allow the differentiation of reversible from irreversible myocardial injury.

Biomarkers↗

Myocardial revascularization with bilateral internal thoracic artery in patients with left main disease or left ventricular dysfunction: an incremental risk?

Although long-term patency of the internal thoracic artery (ITA) is well stated, there is still some concern about its perioperative performance. We considered 122 consecutive patients, 63 with left main disease (LMD; mean age 60 years) and 59 with left ventricular dysfunction (LVD; mean age 59 years) who underwent coronary artery bypass grafting in our Institute from March 1988 to September 1992. Patients with LMD were divided into 2 groups: LMD I: 29 patients receiving only ITA grafts on the left coronary system and LMD II: 34 patients having a single ITA graft on the left coronary system. Patients with LVD were divided into: LVD I: 44 patients operated with bilateral ITA and LVD II: 15 patients receiving a single ITA graft. Perioperative complications in LMD I and LMD II patients were respectively: myocardial necrosis in 2 (6.9%) versus 3 (8.8%), use of intra-aortic balloon pump (IABP) in 2 (6.9%) versus 2 (5.9%); no death occurred in both groups. Perioperative results in groups LVD I and LVD II were: death in 1 patient (2.2%) versus 1 (6.7%), myocardial necrosis in 2 (4.5%) versus 1 (6.7%) and IABP in 4 (9.1%) versus 2 (13.3%). In our experience the use of bilateral ITA grafts in patients with LMD and LVD was not related to an incremental risk. We conclude that LMD and LVD should not be considered as contraindications to the extensive use of arterial conduits.

Aged↗

Rest and exercise hemodynamics of stentless porcine bioprostheses in aortic position.

Mechanical and conventional stented bioprostheses, because of need for anticoagulants, hemodynamic characteristics and long-term durability, do not represent the optimal heart valve replacement device. In this study we compared the hemodynamic function of a stented aortic bioprosthesis (St Jude Bioimplant), implanted in 10 patients, with a stentless porcine aortic bioprosthesis (Biocor) implanted in 7 patients, by means of Doppler echocardiography early postoperative at rest (T1) and 6 months later at rest (T2a) and during exercise (T2b). Mean and peak systolic gradients across stentless porcine prostheses were significantly lower than across stented bioprostheses (T1 p = 0.008 and p = 0.004; T2a p < 0.0001 and p < 0.0001; T2b p < 0.0001 and p < 0.0001, respectively). Our results show that systolic and diastolic mechanical stress on biological components of a glutaraldehyde-fixed stentless porcine aortic bioprosthesis is much lesser than on stented bioprostheses. This feature has appeared evident at rest and much more after exercise testing. The reduction of systolic and diastolic stress is expected to determine lower calcification degree and longer durability of stentless porcine aortic bioprostheses. Moreover, aortic valve replacement by means of stentless bioprostheses allows the implantation of a 1 size (2 mm) larger device, appearing favourable especially in small aortic annulus. On the basis of these promising results we suggest that stentless bioprostheses are a valid alternative to stented bioprostheses for aortic valve replacement. However, patient population is too small and the follow-up is too short to draw a definite statement about long-term hemodynamic performance of this device.

Aged↗

[Myocardial revascularization in patients with impaired left ventricular function].

From March 1988 to May 1993, 1,125 patients with coronary artery disease (CAD) underwent coronary surgery at our Institute. In the same period 74 patients (mean age 59 +/- 7 years; range 36-73) with left ventricular dysfunction (LVD) were referred for surgical decision making. All patients underwent [99mTc]MIBI/SPET to assess perfusion at rest and [99mTc]MIBI first pass radionuclide angiography to assess the ejection fraction (EF). In 44/74 patients we performed [18F]FDG/PET in fasting conditions and pharmacologic wash-out, in order to identify viable myocardium. We divided patients with LVD into 3 groups: Group A (30 patients) operated on without preoperative [18F]FDG/PET, Group B (37 patients) operated on with FDG uptake in segments with wall motion abnormalities, and Group C (7 patients) with no FDG uptake, who were excluded from coronary surgery; there was no significant difference among the 3 groups with respect to age, sex, CAD, risk factors and EF (Group A: 29.1% +/- 6.6%, range 16-39%; Group B: 30.8 +/- 5.6%, range 20-40%; Group C: 26.5 +/- 6.8%, range 18-37%). The study of perfusion and EF was repeated 6 months postoperatively in Group A and B. Left ventricular end-dyastolic pressure at cardiac catheterization was 19.9 +/- 5.1 mmHg, 20.4 +/- 4.7 mmHg and 26.8 +/- 9.2 mmHg in Group A, B and C, respectively. Myocardial protection was achieved according to the Buckberg protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial revascularization in patients with severe ischaemic left ventricular dysfunction: a clinical experience.

The benefits of myocardial revascularization in patients with ischaemic left ventricular dysfunction are widely reported. However, myocardial revascularization in such cases is associated with higher mortality and morbidity rates. Sixty patients with severe left ventricular dysfunction underwent myocardial revascularization at the authors' institution. Ejection fraction was assessed by angiocardioscintigraphy before and at 3 months after surgery. All patients underwent elective surgery and received complete myocardial revascularization. Myocardial protection was achieved using Buckberg's protocol. One perioperative death occurred. Weaning from cardiopulmonary bypass required inotropic drug therapy in 22 cases and aortic counterpulsation in nine. Perioperative myocardial infarction occurred in three patients with no further haemodynamic impairment. The mean postoperative ejection fraction was 41.0%, compared with a mean preoperative value of 26.5%. The extent of left ventricular functional improvement was greatest in those patients having the worst preoperative left ventricular function. It is concluded that, with this technique, myocardial revascularization can be achieved in patients with severe left ventricular dysfunction with an acceptable operative mortality.

Aged↗

Effects of cyclosporin A on erythropoietin production by the human Hep3B hepatoma cell line.

There is evidence that the inadequate erythropoietin (Epo) production observed in patients undergoing allogeneic bone marrow transplantation (BMT) might be ascribed to an inhibitory effect caused by the immunosuppressive drug cyclosporin A (CsA). In this in vitro study, we have evaluated the effects of CsA on the release of Epo in the culture medium by the human Hep3B hepatoma cell line. In cultures incubated with both CsA and the nonimmunosuppressive CsA analog MeAla-6, but not with the CsA-unrelated immunosuppressive agent FK-506, the levels of Epo in the medium were significantly reduced in comparison with controls, at concentrations (0.01 to 1.6 mumol/L) not affecting total protein synthetic rate nor the constitutive secretion of alpha-fetoprotein. Hep3B cells were found to contain a CsA-binding molecule, with an M(r) of 18 Kd, as assessed by high performance liquid chromatography (HPLC) and ligand-blotting analysis. CsA did not affect the expression of the Epo gene, as judged by Northern blot analysis, but caused a significant amount of Epo to remain unsecreted within the cells; almost all (97% of total) of the intracellular Epo was associated with the plasma membrane subcellular fraction. We conclude that: (1) CsA is able to inhibit Epo release in vitro by Hep3B cells, further supporting the hypothesis that the drug might have a role in the inappropriately low Epo levels observed in BMT patients; (2) the inhibitory effect appears to be specific and not caused by a general impairment of protein synthesis and/or secretion; and (3) the reduced Epo levels found in the medium of CsA-treated Hep3B cultures are supposed to be the consequence of an inability of the cells to correctly process Epo molecules for the secretory pathway.

Amino Acid Isomerases↗

Effect of the enhancement of the cholinergic tone by pyridostigmine on the exercise-induced growth hormone release in man.

We have evaluated the effect of pyridostigmine (PD), a cholinergic agonist, on the growth hormone (GH) response to physical exercise (EXC) in nine healthy volunteers. PD administration and EXC caused a similar increase of GH secretion to mean (+/- SE) peak values of 5.3 +/- 0.9 and 6.5 +/- 1.2 micrograms/l, respectively. Pretreatment with PD caused a significant augmentation of the EXC-induced GH release evaluated both as maximum peak (13.5 +/- 2.1 micrograms/l, p < 0.01 vs EXC) and as area under the secretory curve (EXC = 292.6 +/- 41.9 micrograms.min.l; PD + EXC = 587.3 +/- 68.9 micrograms.min.l, p < 0.005). The action of PD on GH secretion was additive to that of EXC since the sum of the GH responses to PD and EXC was not significantly different from the response obtained during PD + EXC. Whether PD and EXC act through a common final pathway, i.e. inhibition of endogenous somatostatin release, or the EXC-induced GH secretion involves stimulation of endogenous GHRH remains matter of investigation.

Adult↗