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Biomedical subjects

A Grossi

Publications and source records attributed to A Grossi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Regioselective synthesis and biological profiling of butyric and phenylalkylcarboxylic esters derivated from D-mannose and xylitol: influence of alkyl chain length on acute toxicity.

Regiospecific synthesis of 12 novel n-butyric and phenylalkylcarboxylic monoesters of mannose and xylitol was achieved. The strategy adopted, avoided a tedious intramolecular transesterification step, previously described for the synthesis of analogous compounds and permitted the facile synthesis of a new generation of stable derivatives. The general tolerance of the drugs has been assayed after intravenous administration of a bolus dose into mice. Monobutyric esters showed a low toxicity commensurate with the requirements for future development. A relationship was observed between chain length and toxicity. In contrast, phenylacetic, 3-phenylpropionic and 4-phenylbutyric esters were found to be toxic. Phenylbutyric esters induced marked and specific neuromuscular damage. Preliminary biological investigations of the new series of monobutyric esters showed them to retain the benificial biological properties of butyric acid whilst remaining relatively non toxic. They induced an inhibition of in vitro proliferation of 10 human cases of de novo acute myeloid leukemia (AML) primary cultures and AML established cell lines. AML blasts growth appeared to be blocked and cell differentiation was established. Transcription and expression of maturation markers and finally apoptosis were observed. Moreover, human gamma-chain hemoglobin (HbF) synthesis in erythroleukemia cells was stimulated by monobutyric esters. Mannose and xylitol butyric derivatives would appear to have exciting potential in treatment of beta-Hemoglobinopathies, sickle cell anemia and cancer.

Animals↗
PubMed1999

The Italian Consensus Conference on Diagnostic Criteria for Myelofibrosis with Myeloid Metaplasia.

The purpose of this work was to develop a definition of myelofibrosis with myeloid metaplasia (MMM) using diagnostic criteria that would remain valid within the set of patients with chronic myeloproliferative disorders or myelodysplastic syndromes. A list of 12 names for the disease and 37 diagnostic criteria were proposed to a Consensus Panel of 12 Italian experts who ranked them in order so as to identify a core set of criteria. The Panel was then asked to score the diagnosis of 46 patient profiles as appropriate or not appropriate for MMM. Using the experts' consensus as the gold standard, the performance of 90 possible definitions of the disease obtained through the core set was evaluated. 'Myelofibrosis with myeloid metaplasia' ranked as the preferred name of the disease. Necessary criteria consisted of 'diffuse bone marrow fibrosis' and 'absence of Philadelphia chromosome or BCR-ABL rearrangement in peripheral blood cells'. The six optional criteria in the core set consisted of: splenomegaly of any grade; anisopoikilocytosis with tear-drop erythrocytes; the presence of circulating immature myeloid cells; the presence of circulating erythroblasts: the presence of clusters of megakaryoblasts and anomalous megakaryocytes in bone marrow sections; myeloid metaplasia. The definition of the disease with the highest final score was as follows: necessary criteria plus any other two criteria when splenomegaly is present or any four when splenomegaly is absent. The use of this definition will help to standardize the conduct and reporting of clinical studies and should help practitioners in clinical practice.

Humans↗
PubMed1999

[Laryngotracheal resection and reconstruction by Grillo's technic for postintubation stenosis].

BACKGROUND: Tracheal resection and reconstruction is the standard treatment for postintubation stenosis. However, when the stenosis extends proximally to the subglottic larynx surgical treatment is particularly difficult. Specific surgical techniques have to be used in order to preserve the recurrent laryngeal nerves. The aim of this study is to evaluate the results obtained at our Department with laryngotracheal resection and reconstruction with the Grillo technique for postintubation stenosis. METHODS: From January 1984 to December 1997, 83 patients with tracheal and laryngotracheal lesions underwent surgical treatment. Eighteen patients had postintubation stenosis of the upper trachea and subglottic larynx and underwent single-stage laryngotracheal resection and reconstruction. Mean stenosis length was 3.5 cm (range 3-5 cm). Twelve patients underwent anterolateral laryngotracheal reconstruction, and 6 patients had a circumferential laryngotracheal reconstruction. A Montgomery suprahyoid laryngeal release was required in 4 cases. RESULTS: There was no surgical mortality. Surgical results were excellent or good in 17 cases and satisfactory in one case. No recurrence of stenosis has been observed. CONCLUSIONS: Cricoid cartilage involvement in postintubation stenosis should not be considered a contraindication to surgical treatment. However, laryngotracheal resection and reconstruction is technically difficult and should be performed only in selected cases.

Adolescent↗
PubMed1999

Assessment of CABG-related risk in patients with CAD and LVD. Contribution of PET with [18F]FDG to the assessment of myocardial viability.

BACKGROUND: Previous studies have demonstrated that hibernating myocardium can be assessed by [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). This study evaluated the use of [18F]FDG-PET for CABG related risk assessment in patients with coronary artery disease (CAD) and left ventricle dysfunction (LVD). METHODS: We retrospectively evaluated 241 to patients candidate CABG presenting with signs and symptoms of congestive heart failure (CHF) prevailing over ischemic signs. Of the 241 patients, 153 had undergone [18F]FDG-PET as well as conventional assessment: 110 out of 153 (group A) were operated because of PET evidence of hibernation. Of the 241 patients, 88 had not undergone [18F]FDG-PET: 86 out of 88 (group B) were operated on. The outcome of surgical patients was evaluated by considering all major perioperative complications including the use of mechanical and pharmacological support and in-hospital mortality. After hospital discharge, each patient was examined at 1, 4 and every 6 months thereafter. RESULTS: Perioperative use of mechanical supports and inotropic drugs, was significantly lower for the PET selected group (A) than for the non PET selected group (B). Mortality within 30 days of surgery was 0.9% in group A and 19.8% in group B. The only predictors of perioperative outcome were the presence of hibernating tissue and the ejection fraction. CONCLUSIONS: [18F]FDG-PET prior to CABG can be crucial for the assessment of perioperative risk in patients with CAD.

Coronary Artery Bypass↗
PubMed1999

Induction of apoptosis by monosaccharide butyrate stable derivatives in chronic lymphocytic leukemia cells.

BACKGROUND AND OBJECTIVE: Different therapeutic approaches are needed to restore apoptotic mechanisms in CLL cells, as present ones are not successful. We assessed the apoptotic effects of stable butyrate derivatives on CLL lymphocytes: in these molecules a mannose molecule is bound as ester to one-five butyrate moieties, conferring pharmacological stability to the pro-drugs which are able to induce apoptosis in primary AML blasts. DESIGN AND METHODS: Peripheral blood samples obtained from 17 patients with typical B-CLL were cultured in the presence of 0.5-1mM D1 (O-n-butanoyl-2, 3-O-isopropylidene-a-D-mannofuranoside), F1 (1-O-n-butanoyl-2, 3-O-isopropylidene-D,L-xylitol) and G1 (1-O-n-butanoyl-D,L-xylitol) derivatives for 4 days and equimolar sodium butyrate as comparison. After culture, apoptosis was evaluated by cell morphology, cellular DNA content, pattern of DNA fragmentation, annexin V exposure on cell membrane, and cell cycle parameters. Bcl2, bax, and fas oncogene expression were also evaluated by the APAAP method. RESULTS: The addition to cell cultures of D1 or F1 or G1 butyrate monosaccharides as well as sodium butyrate 0.5 and 1 mM determined to different extents an increase in the percentage of apoptotic cells in all CLL samples, relatively to the method and butyrate molecule added in culture. Heterogeneity in CLL cell sensitivity to the three butyrates was observed. Up to 60-68% apoptotic bodies were present in treated cultures after exposure to D1 0.5-1 mM, 60-72% after F1 0.5-1 mM and 48-60% after G1 0.5-1 mM. Comparison of untreated versus treated cultures yielded important significance (p< 0.001). At DNA content analysis, analyzed by flow cytometry, apoptotic events were accounting for up to 70-77% of D1-treated and 68-74% of F1-treated CLL cells at 0.5 and 1 mM concentrations (p= 0. 0001, vs controls 0-39%), and for 72-81% of G1 (0.5-1 mM) treated cells (overall, p=0.005). Cell cycle parameters were not altered by addition of butyrates, but expression of Annexin V was greatly enhanced. In a limited number of CLL cases fas, bcl2/bax ratio was analyzed and found unmodified. INTERPRETATION AND CONCLUSIONS: Monosaccharide butyrate stable derivatives are potent inducers of primary CLL cell apoptosis, both in untreated and alkylating agent pre-treated cases. Our results suggest that the apoptotic pathways elicited by butyrate in CLL lymphocytes are direct, specific and most probably do not involve bcl2/bax. Pro-apoptotic agents like the stable monosaccharide butyrate derivatives here studied could bring more insights into CLL biology and resistance to apoptosis, and possibly originate alternative treatments for CLL.

Aged↗
PubMed1999

Plasma lipoproteins affect rate of cholesterol absorbed from bile by gallbladder: preliminary data.

BACKGROUND: The excessive accumulation of cholesterol absorbed from bile by the gallbladder impairs its contractility and favours gallstone formation. The total low plasma and high density lipoprotein cholesterol concentrations are associated with gallstone disease. AIMS: To investigate the effect of plasma lipoproteins on gallbladder cholesterol and phosphatidylcholine absorption from bile and to establish whether cholesterol absorption is Brefeldin A-sensitive. METHODS: Gallbladder mucosa lipid absorption rates were measured using: 1) in vitro isolated intra-arterially perfused pig gallbladder model with and without plasma lipoproteins perfusing the vascular tree; 2) human gallbladder fragments mounted in Ussing chambers with plasma lipoproteins at different concentrations in the serosal side; 3) pig gallbladder fragments mounted in Ussing chambers in the presence and absence of Brefeldin A. RESULTS: Total lipoproteins and high density lipoprotein significantly increased the release of biliary cholesterol and phosphatidylcholine in plasma and significantly decreased the tissue accumulation of cholesterol absorbed from bile. The scavenger effect of plasma lipoproteins on cholesterol absorbed from bile was concentration dependent. Brefeldin A did not influence gallbladder absorption of biliary cholesterol. CONCLUSIONS: Biliary cholesterol is absorbed by gallbladder mucosa via a Brefeldin-insensitive pathway and is removed by plasma lipoproteins.

Absorption↗
PubMed1999

[High-risk pulmonary surgery in potential candidates for a heart transplant].

Severe ventricular dysfunction and concomitant infection are considered absolute contraindications for major thoracic operations and immunosuppressive therapy, respectively. However, cardiac transplantation represents the first-choice treatment in advanced heart failure. We report the case of a patient with dilated cardiomyopathy and severe left ventricular dysfunction (ejection fraction = 25%), initially not considered as a potential heart transplant candidate due to the presence of a lung abscess. The patient subsequently underwent atypical pulmonary resection with intraoperative and perioperative intraaortic balloon counter-pulsation for circulatory support and was then listed for cardiac transplant. Pitfalls and intra/postoperative strategy, all of which are potentially important aspects in minimizing operative risk, are discussed.

Cardiomyopathy, Dilated↗
PubMed1998

Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia.

An unexpectedly high incidence of blast transformation after splenectomy has been reported in patients with myelofibrosis with myeloid metaplasia. However, whether this was associated with spleen removal after adjustment for risk factors was not determined. We conducted a multicenter historical cohort study of patients with myelofibrosis with myeloid metaplasia diagnosed from January 1970 through January 1994. A total of 549 patients (325 men and 224 women from 22 to 92 years of age; median age, 63 years) were included in the final data set. The Cox's proportional-hazards model was used to identify factors associated with blast transformation and death. To further adjust for factors related to spleen removal assignment, a propensity score for splenectomy was estimated using recursive-partitioning analysis. Blast transformation developed in 78 patients (14.2%). Patients who underwent splenectomy developed more blast transformations than those who were not splenectomized (23 of 87 [26.4%] v 55 of 462 [11.9%]; P < .001). The cumulative incidence of blast transformation 12 years after diagnosis was 27.0% in nonsplenectomized patients and 55.0% in splenectomized ones (P = . 01). The risk factors independently predictive of blast transformation included prior splenectomy (relative risk = 2.61), platelet count less than 100 x 10(9)/L at diagnosis (relative risk = 2.45), and the presence of blasts in peripheral blood at diagnosis (relative risk = 2.31). The relative risk of blast transformation in splenectomized patients increased from 2.2 at 48 months from diagnosis to 14.3 at 12 years. Patients with the same propensity score for splenectomy showed a higher risk for blast transformation on the basis of having undergone splenectomy (P = .02). In conclusion, the risk of blast transformation is significantly increased in subjects who underwent splenectomy and appears to be independent of factors related to spleen removal assignment.

Adult↗
PubMed1998

Portal thrombosis. A rare complication of laparoscopic splenectomy.

Portal thrombosis is a rare complication of splenectomy. We performed 12 laparoscopic splenectomies and observed this complication only in one patient with idiopathic thrombocytopenia (ITP). The right branch of the portal vein presented a partial thrombosis, while the left branch was completely obstructed by thrombi. Abdominal ultrasonography and an ultrasound doppler exam allowed us to diagnose this event and a retrograde angiography performed afterward confirmed our diagnosis. A 48-h intravenous heparin treatment was promptly begun, followed by anticoagulant drugs (dicumarol). The patient was dismissed 5 days afterward, presenting a steady-state ultrasound doppler pattern and a complete normalization of liver parameters. An ultrasound doppler exam performed 1 month after anticoagulant therapy showed a complete resolution of portal thrombosis. We believe that early diagnosis of this rare complication, prompt beginning of anticoagulant therapy, and care in surgical procedures may reduce patient life-threatening risks and assure complete remission.

Adult↗
PubMed1998

Myocardial metabolism studied during warm blood antero-retrograde reperfusion in ischaemic human hearts.

We propose modified warm blood antegrade-retrograde reperfusion (WBARR) of arrested hearts as a metabolic model with which to study substrate exchange and energy metabolism during the recovery phase after 90 min of ischaemia in man. Eleven anaesthetized patients undergoing aorto-coronary bypass were studied during WBARR. The protocol was designed as follows: period 1, a warm blood reperfusion with potassium (3 min); period 2, a warm blood reperfusion without potassium (2 min). The perfusion flow rate averaged 250+/-2 ml/min at the beginning of period 1 and 218+/-19 ml/min at the beginning and at the end of period 2; the perfusion was performed antegradely and retrogradely in the arrested hearts. Samples were simultaneously taken from the coronary venous sinus (CVS) and from the aortic root needle (AR). At the beginning of WBARR lactate release was 85+/-44 micromol/min and at the end it had significantly decreased to 21+/-99 micromol/min (P<0.03). Simultaneously, non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate were initially released (71+/-61 and 22+/-66 micromol/min, respectively), while at the end of the WBARR there was an uptake of both NEFA (20+/-22 micromol/min; P<0.01) and beta-hydroxy-butyrate (12+/-35 micromol/min; P=0.290). Alanine, glycerol and branched chain amino acid balance across the heart did not significantly change. In summary after 90 min of ischaemia the heart energy metabolism is mainly anaerobic and based on glucose consumption, with lactate, NEFA and amino acids, which are mainly released. After 5 min of WBARR (recovery from ischaemia), lactate release is significantly reduced and NEFA becomes the energy supply of the heart. In conclusion, (1) WBARR is a valuable method with which to study myocardial metabolism in anaesthetized humans and may be combined with the use of tracers; (2) the study of myocardial metabolism in arrested hearts eliminates the imprecisions arising from the noncontinuous coronary blood flow; (3) NEFA become an important source of energy utilized by human hearts in the recovery phase from ischaemia.

Adult↗
PubMed1998

Mycotic aortic aneurysm presenting as multiple cerebral abscesses.

A 68-year-old male presented with multiple cerebral abscesses. Possible intrathoracic embolic sources were not detected by echocardiography and chest radiography and the main lesion was surgically excised. Following deterioration of the neurological status, computerized tomography performed 2 weeks later revealed a mycotic aneurysm of the ascending aorta, probably related to a previous cardiac operation. This is the first case in the literature of aortic infection presenting as multiple brain abscesses.

Aged↗
PubMed1998

In search of biological markers of high-risk carotid artery atherosclerotic plaque: enhanced LDL oxidation.

The oxidation of low density lipoprotein (LDL) is a key event in the development and progression of atherosclerosis because it generates molecular epitopes that are more atherogenic than parent LDL. We found previously that patients with carotid atherosclerosis have a significantly higher titer of autoantibodies against oxidatively modified LDL than normal subjects. The aim of this study is to correlate biological markers of in vivo LDL oxidation with the degree of carotid stenosis and of plaque ulceration (PU) in a series of patients undergoing carotid endoarteriectomy (CEA). Ninety-four consecutive patients (68M and 26F, aged 67.3 +/- 8.2 years) who underwent CEA at our institution between June 1993 and January 1994 were included in the study. The degree of carotid stenosis and the presence and extent of PU were correlated with the level of autoantibodies (IgG) against oxidatively modified LDL (Cu++-oxidized [oxLDL] or malondialdehyde derivatized LDL [MDA-LDL]), that consistently mirrors the occurrence of oxidative modifications in vivo. A statistically significant correlation (r = 0.23, p = 0.039) was found between the degree of carotid stenosis and antiMDA-LDL specific ratio (a parameter that describes the specificity of LDL towards other proteins as target for oxidative modification). A statistically significant correlation was also found between the PU score and antioxLDL IgG (r = 0.32, p = 0.011), antiMDA-LDL IgG (r = 0.25, p = 0.045) and antiMDA-LDL IgG specific ratio (r = 0.38, p = 0.002). None of the classical biochemical parameters (total, LDL and HDL cholesterol and triglycerides) correlated with the above-mentioned plaque characteristics. The results shown, support the use of biological markers of in vivo LDL oxidation (antioxidatively modified LDL autoantibody titers) to evaluate the clinical setting of high-risk carotid atherosclerosis both in screening and in follow-up studies.

Aged↗
PubMed1998

Erythropoietin upregulates the expression of its own receptor in TF-1 cell line.

In the erythroleukemia cell line TF-1, recombinant human erythropoietin (rHEpo), but not c-kit ligand, enhanced the number of cells expressing the erythropoietin receptor (EpoR), as measured by flow-cytometric analysis of binding of the biotin-labeled Epo. Moreover, 125I-Epo binding and Scatchard analyses, indicated that TF-1 cells, maintained in standard conditions with IL-3, and those stimulated with c-kit ligand, bear a single class of EpoR. On the other hand, cells cultured in the presence of rHEpo had a higher number of receptors than IL-3 or c-kit ligand-stimulated cells, and had two binding sites with different affinities for the ligand. EpoR mRNA expression was higher in cells exposed to rHEpo than in IL-3 or c-kit-stimulated cells. This difference may have been dependent on either a higher level of transcription or an increased stability of mRNA. The observed changes of EpoR in rHEpo-stimulated TF-1 cell line could cooperate, together with the alteration of the gene (3' end deletion), in the occurrence of the erythroleukemic process. Changes induced in EpoR by rHEpo were not accompanied by an increase in the expression of glycophorin A or globin chain mRNAs. This may suggest that rHEpo is unable to induce erythroid differentiation in TF-1 cells. The results also indicate that this cell line could be a model for the investigation of the role of transcription factor(s) in the expression of EpoR, and for the study of the mechanism(s) underlying the changes in the number and affinity of the cell receptors.

Erythropoietin↗
PubMed1998

Surgery of cavo-atrial renal carcinoma employing circulatory arrest: immediate and mid-term results.

From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent resection of the tumor. Circulatory arrest was employed in 11/12 cases. The neoplasm extended to the inferior vena cava in two patients and to the intrahepatic veins or right atrium in five cases. Two severely cardiac compromised patients died perioperatively. Of five patients who showed preoperative suspicion of isolated metastases, 3 patients died postoperatively because of relapsing disease after a mean period of 10.8 months. Five patients are alive and doing well after a mean follow-up of 14.8 months. In our experience myocardial dysfunction determined poor immediate survival. Mid-term survival was influenced by preoperative metastases and lymph-node involvement, but not by intracaval extension. Circulatory arrest appears to be a relatively safe technique to remove renal carcinoma with cavo-atrial extension and should be indicated whenever there are no metastases.

Adult↗
PubMed1998

Combined carotid and cardiac procedures: improved results and surgical approach.

Severe cerebrovascular complications following cardiac surgical procedures remain a major concern, particularly in patients with significant carotid atherosclerotic involvement (14% of perioperative stroke). Operative mortality for carotid operations in patients with documented Coronary Artery Disease (CAD) may be as high as 20%. Seventy patients underwent combined operations (unilateral carotid stenosis > 70%, unilateral stenosis > 50% with ulcerated plaque or bilateral stenoses > 50%; and this also included patients with unilateral occlusion). Cardiac procedures were 69 coronary artery bypass grafts, four left ventricular aneurysmectomies, three aortic valve replacements and surgery on two mitral valves. Seven perioperative deaths occurred, which were all caused by cardiac events. There were no perioperative strokes. Carotid endarterectomy immediately before cardiopulmonary bypass is a safe and expeditious approach to coexisting significant cardiac and carotid disease. In our experience, technical details in monitoring and minimizing cerebral ischemia are possibly more crucial in these severe vasculopathic patients. Moreover, it is probably advantageous from an economic standpoint compared with other therapeutic treatments.

Aged↗
PubMed1998

Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukaemia cells.

The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo has been improved by the synthesis of monosaccharide stable pro-drugs of butyric acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D-mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O-isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute myeloid leukaemia (AML). AML cell maturation was measured by surface antigen expression, morphology and cytochemistry. Toxicology in mice was also evaluated (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1 and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1 (27%). The persistence of maturative and apoptotic activity in these new pro-drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a possible use in differentiation therapy of myelodysplastic syndromes and AMLs.

Acute Disease↗
PubMed1998

Coexpression of erythroid and megakaryocytic genes in acute erythroblastic (FAB M6) and megakaryoblastic (FAB M7) leukaemias.

There is evidence to suggest a close relationship between the erythroid and megakaryocytic lineages. Using RT-PCR, we evaluated the coexpression of erythroid and megakaryocytic genes in blasts from 25 acute myeloid leukaemia (AML) cases (FAB M1-M7) and three unclassifiable leukaemias with trilineage dysplasia (trilineal AML). All FAB M6 and M7 and trilineal leukaemias expressed mRNAs for alpha-globin, glycoprotein IIb (GpIIb), erythropoietin receptor (Epo-R) and thrombopoietin receptor (c-mpl), but not for myeloperoxidase (MPO) which in contrast was expressed in the other FAB-subtype leukaemias. These data support the hypothesis that blasts from M7 and M6 leukaemias may derive from (or represent) a common progenitor cell with resident bipotentiality towards the megakaryocytic and erythrocytic lineages.

Base Sequence↗