Search PubMed⌕ Search

Biomedical subjects

M Lombardi

Publications and source records attributed to M Lombardi.

At least 19 recordsLinked to original sources
PubMed2003

Automated cardiac MR image segmentation: theory and measurement evaluation.

We present a new approach to magnetic resonance image segmentation with a Gradient-Vector-Flow-based snake applied to selective smoothing filtered images. The system also allows automated image segmentation in the presence of grey scale inhomogeneity, as in cardiac Magnetic Resonance imaging. Removal of such inhomogeneities is a difficult task, but we proved that using non-linear anisotropic diffusion filtering, myocardium edges are selectively preserved. The approach allowed medical data to be automatically segmented in order to track not only endocardium, which is usually a less difficult task, but also epicardium in anatomic and perfusion studies with Magnetic Resonance. The method developed proceeds in three distinct phases: (a) an anisotropic diffusion filtering tool is used to reduce grey scale inhomogeneity and to selectively preserve edges; (b) a Gradient-Vector-Flow-based snake is applied on filtered images to allow capturing a snake from a long range and to move into concave boundary regions; and (c) an automatic procedure based on a snake is used to fit both endocardium and epicardium borders in a multiphase, multislice examination. A good agreement (P<0.001) between manual and automatic data analysis, based on the mean difference+/-SD, was assessed in a pool of 907 cardiac function and perfusion images.

Algorithms↗
PubMed2002

Numerical construction of "optimal" nonoscillating amplitude and phase functions.

A numerical recipe for the construction of nonoscillating amplitude and phase functions for potentials with a single minimum is given. We give different examples illustrating the recipe, showing the usefulness of the procedure for the construction of basis functions in bound-state scattering processes, such as those described by quantum defect theory. The resulting amplitude and accumulated phase functions are coined as "optimal" nonoscillating (as a function of the space and energy variables) because they are the counterpart for the quantum problem of the classical action for the analog semiclassical problem.

Journal Article↗
PubMed2002

Sex steroid hormones act as growth factors.

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

3T3 Cells↗
PubMed2002

[Laparoscopic surgical treatment in abdominal emergencies: personal experience].

In recent years laparoscopic surgery has reached a crucial role in the surgical approach of both abdominal and thoracic pathologies. A diffused as elective surgery, its utilization has become necessary even in emergency surgery, both as diagnostic approach as curative aim. In this work the purpose of the Authors is to show their own experience in a six years period in the laparoscopic treatment of abdominal emergencies.

Abdomen↗
PubMed2001

PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells.

The p85-associated phosphatidylinositol (PI) 3-kinase/Akt pathway mediates the oestradiol-induced S-phase entry and cyclin D1 promoter activity in MCF-7 cells. Experiments with Src, p85alpha and Akt dominant-negative forms indicate that in oestradiol-treated cells these signalling effectors target the cyclin D1 promoter. Oestradiol acutely increases PI3-kinase and Akt activities in MCF-7 cells. In NIH 3T3 cells expressing ERalpha, a dominant-negative p85 suppresses hormone stimulation of Akt. The Src inhibitor, PP1, prevents hormone stimulation of Akt and PI3-kinase activities in MCF-7 cells. In turn, stimulation of Src activity is abolished in ERalpha-expressing NIH 3T3 fibroblasts by co-transfection of the dominant-negative p85alpha and in MCF-7 cells by the PI3-kinase inhibitor, LY294002. These findings indicate a novel reciprocal cross-talk between PI3-kinase and Src. Hormone stimulation of MCF-7 cells rapidly triggers association of ERalpha with Src and p85. In vitro these proteins are assembled in a ternary complex with a stronger association than that of the binary complexes composed by the same partners. The ternary complex probably favours hormone activation of Src- and PI3-kinase-dependent pathways, which converge on cell cycle progression.

Breast Neoplasms↗
PubMed2001

Relationship between function and perfusion early after acute myocardial infarction.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p < 0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p < 0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p < 0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

Adrenergic beta-Agonists↗
PubMed2001

Effects of estrogen therapy on arterial resistance and pulsatility in postmenopausal women.

The hypothesis of this study was that changes in arterial determinants of afterload due to static muscular contraction can be modified, in postmenopausal women, by estrogen replacement therapy. Two groups of 14 postmenopausal and 15 premenopausal women were enrolled. Hemodynamic changes induced by right handgrip were recorded between days 7 and 10 of the menstrual cycle in premenopausal women. The same recordings were performed in postmenopausal women, before and after receiving transdermal estrogen replacement therapy for 8 days. Handgrip was performed at 50% of maximal voluntary contraction and maintained until exhaustion. Arterial pressure and blood velocity were recorded in the resting hand with photoplethysmographic and Doppler techniques. Indices of arterial elasticity and resistance were calculated. In postmenopausal women, these indices increased during effort only slightly less after therapy than before, if the mean values and statistical significance were considered, but the most evident effect of therapy was a decrease in interindividual differences in the effort induced changes. This means that, after therapy, increases in arterial resistance and elasticity indices were appreciably prevented mainly in those postmenopausal women who, before therapy, showed the greatest increases. Differences due to therapy were negligible in postmenopausal women in whom, before estrogen replacement, increases in elasticity and resistance indices during effort were similar to those obtained in premenopausal women. After therapy, no differences were found in resting conditions in any of the investigated cardiovascular parameters. Estrogen replacement did not appreciably affect changes in some arterial afterload-related indexes during handgrip, if the average values were considered in a group of postmenopausal women, but uneven and unpredictable peaks in individual responses were cut off, with a better predictability of the responses to sustained muscular contractions, as well as of the related risk factors.

Aged↗
PubMed2000

Steroid-induced androgen receptor-oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation.

Treatment of human prostate carcinoma-derived LNCaP cells with androgen or oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor beta with Src, activates the Src/Raf-1/Erk-2 pathway and stimulates cell proliferation. Surprisingly, either androgen or oestradiol action on each of these steps is inhibited by both anti-androgens and anti-oestrogens. Similar findings for oestradiol receptor alpha were observed in MCF-7 or T47D cells stimulated by either oestradiol or androgens. Microinjection of LNCaP, MCF-7 and T47D cells with SrcK(-) abolishes steroid-stimulated S-phase entry. Data from transfected Cos cells confirm and extend the findings from these cells. Hormone-stimulated Src interaction with the androgen receptor and oestradiol receptor alpha or beta is detected using glutathione S:-transferase fusion constructs. Src SH2 interacts with phosphotyrosine 537 of oestradiol receptor alpha and the Src SH3 domain with a proline-rich stretch of the androgen receptor. The role of this phosphotyrosine is stressed by its requirement for association of oestradiol receptor alpha with Src and consequent activation of Src in intact Cos cells.

Androgen Antagonists↗
PubMed2000

Predicting patient outcome from acute renal failure comparing three general severity of illness scoring systems.

BACKGROUND: A major problem of studies on acute renal failure (ARF) arises from a lack of prognostic tools able to express the medical complexity of the syndrome adequately and to predict patient outcome accurately. Our study was thus aimed at evaluating the predictive ability of three general prognostic models [version II of the Acute Physiology and Chronic Health Evaluation (APACHE II), version II of the Simplified Acute Physiology Score (SAPS II), and version II of the Mortality Probability Model at 24 hours (MPM24 II)] in a prospective, single-center cohort of patients with ARF in an intermediate nephrology care unit. METHODS: Four hundred twenty-five patients consecutively admitted for ARF to the Nephrology and Internal Medicine Department over a five-year period were studied (272 males and 153 females, median age 71 years, interquartile range 61 to 78, median APACHE II score 23, interquartile range 18 to 28). Acute tubular necrosis (ATN) accounted for 68.7% (292 out of 425) of patients. Renal replacement therapies (hemodialysis or continuous hemofiltration) were used in 64% (272 out of 425) of ARF patients. RESULTS: Observed mortality was 39.1% (166 out of 425). The mean predicted mortality was 36.2% with APACHE II (P = 0.571 vs. observed mortality), 39.3% with SAPS II (P = 0.232), and 45.1% with MPM24 II (P < 0.0001). Lemeshow-Hosmer goodness-of-fit C and H statistics were 15.67 (P = 0.047) and 12.05 (P = 0.15) with APACHE II, 32.53 (P = 0.0001), 39.8 (P = 0.0001) with SAPS II, 21.86 (P = 0.005), and 20. 24 (P = 0.009) with MPM24 II, respectively. Areas under the receiver operating characteristic (ROC) curve were 0.75, 0.77, and 0.85, respectively. CONCLUSIONS: The APACHE II model was a slightly better calibrated predictor of group outcome in ARF patients, as compared with the SAPS II and MPM24 II outcome prediction models. The MPM24 II model showed the best discrimination capacity, in comparison with both APACHE II and SAPS II models, but it constantly and significantly overestimated mean predicted mortality in ARF patients. None of the models provided sufficient confidence for the prediction of outcome in individual patients. A high degree of caution must be exerted in the application of existing general prognostic models for outcome prediction in ARF patients.

APACHE↗
PubMed2000

[Digestive endoscopy in children].

Also in the pediatric population the digestive endoscopy became, at this point, a very good diagnostic and operative technique largement used. The endoscopy can explore the upper gastrointestinal tract (esophagus, stomach, duodenum and jejunum) and can investigate the colon and the terminal ileum regarding the lower gastrointestinal tract. Principally, the operative endoscopy concerns emostasis of gastrointestinal bleeding, polipectomy, extraction of foreign bodies, and intestinal dilatations. The patients population submitted to this investigation by now is very wide thanks to the modernization of the instruments and at specialization of gastroenterologist pediatricians: range from newborn, to childhood, adolescence and young adults. The gastroenterologist pediatricians specialization associated to a routine use of amnemonic drugs (benzodiazepine) reduced at the minimum the invasivity of endoscopy; this technique can be considered a good safe procedure and free of important physical and psychic side effects for the young patient.

Child↗
PubMed1999

The differential pattern of tissue-specific expression of ruminant pancreatic type ribonucleases may help to understand the evolutionary history of their genes.

Molecular evolutionary analyses of mammalian ribonucleases have shown that gene duplication events giving three paralogous genes occurred in ruminant ancestors. The enzymes of the bovine species encoded by these genes, isolated from pancreas, brain and seminal vesicles, present similar enzymological properties but distinct structural features. In other ruminant species, genomic sequences orthologous to the bovine genes of pancreas and brain ribonucleases encode active enzymes. In mammalian species other than ruminant artiodactyls, only one gene encoding ribonuclease of the pancreatic type is generally present. In this work, we describe a differential pattern of transcriptional expression of the pancreas and brain ribonuclease genes in the ox species and report transcription of the human ribonuclease gene in brain as well as in pancreas and in mammary gland. We also report the molecular cloning of the gene encoding the bovine seminal ribonuclease in which the structural organization already described for the two paralogous genes is conserved. The seminal RNAase is exclusively expressed in seminal vesicles of Bos taurus, whereas in other ruminant species, the orthologous sequence is a pseudogene. Previous studies from a number of research groups demonstrated that, unlike other mammalian ribonucleases, the seminal enzyme is a covalent dimer, and its unique quaternary structure correlates with special biological activities. The major determinant of dimer formation, i.e. the presence of two adjacent cysteine residues, is absent in the pseudogenes. We advance the hypothesis that the differentiation of distinct expression patterns could represent an important evolutionary determinant for the genes encoding pancreas and brain ribonucleases in ruminants, whereas the differentiation of a quaternary structure endowed with new biological functions could be the main determinant for the evolutionary success of the seminal gene in the bovine species.

Amino Acid Sequence↗
PubMed1999

Assessment of trigeminal small-fiber function: brain and reflex responses evoked by CO2-laser stimulation.

Laser pulses selectively excite mechano-thermal nociceptors and evoke brain potentials that may reveal small-fiber dysfunction. We applied CO2-laser pulses to the perioral and supraorbital regions and recorded the scalp laser-evoked potentials (LEPs) and reflex responses in the orbicularis oculi, masticatory, and neck muscles in 30 controls and 10 patients with facial sensory disturbances. Low-intensity pulses readily evoked scalp potentials consisting of a negative component with a latency of 165 ms followed by a positive component at 250 ms. In vertex recordings, the amplitude of LEPs exceeded 30 microV. Although only high-intensity pulses evoked reflex responses, some subjects showed--even to low-intensity pulses--an orbicularis oculi (blink-like) response that markedly contaminated the scalp recording. Scalp LEPs were abnormal in patients with hypalgesia and normal trigeminal reflexes and normal in patients with normal pain sensitivity and abnormal trigeminal reflexes. Possibly because of the high receptor density in this area and the short conduction distance, laser stimulation of the trigeminal territory yields low-threshold and large LEPs, which are useful for detecting dysfunction in peripheral and central pain pathways.

Adult↗
PubMed1999

Use of the mean transit time of an intravascular contrast agent as an exchange-insensitive index of myocardial perfusion.

A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.

Animals↗
PubMed1999

Prevalence and clinical outcome associated with preexisting malnutrition in acute renal failure: a prospective cohort study.

Malnutrition is a frequent finding in hospitalized patients and is associated with an increased risk of subsequent in-hospital morbidity and mortality. Both prevalence and prognostic relevance of preexisting malnutrition in patients referred to nephrology wards for acute renal failure (ARF) are still unknown. This study tests the hypothesis that malnutrition is frequent in such clinical setting, and is associated with excess in-hospital morbidity and mortality. A prospective cohort of 309 patients admitted to a renal intermediate care unit during a 42-mo period with ARF diagnosis was studied. Patients with malnutrition were identified at admission by the Subjective Global Assessment of nutritional status method (SGA); nutritional status was also evaluated by anthropometric, biochemical, and immunologic parameters. Outcome measures included in-hospital mortality and morbidity, and use of health care resources. In-hospital mortality was 39% (120 of 309); renal replacement therapies (hemodialysis or continuous hemofiltration) were performed in 67% of patients (206 of 309); APACHE II score was 23.1+/-8.2 (range, 10 to 52). Severe malnutrition by SGA was found in 42% of patients with ARF; anthropometric, biochemical, and immunologic nutritional indexes were significantly reduced in this group compared with patients with normal nutritional status. Severely malnourished patients, as compared to patients with normal nutritional status, had significantly increased morbidity for sepsis (odds ratio [OR] 2.88; 95% confidence interval [CI], 1.53 to 5.42, P < 0.001), septic shock (OR 4.05; 95% CI, 1.46 to 11.28, P < 0.01), hemorrhage (OR 2.98; 95% CI, 1.45 to 6.13, P < 0.01), intestinal occlusion (OR 5.57; 95% CI, 1.57 to 19.74, P < 0.01), cardiac dysrhythmia (OR 2.29; 95% CI, 1.36 to 3.85, P < 0.01), cardiogenic shock (OR 4.39; 95% CI, 1.83 to 10.55, P < .001), and acute respiratory failure with mechanical ventilation need (OR 3.35; 95% CI, 3.35 to 8.74, P < 0.05). Hospital length of stay was significantly increased (P < 0.01), and the presence of severe malnutrition was associated with a significant increase of in-hospital mortality (OR 7.21; 95% CI, 4.08 to 12.73, P < 0.001). Preexisting malnutrition was a statistically significant, independent predictor of in-hospital mortality at multivariable logistic regression analysis both with comorbidities (OR 2.02; 95% CI, 1.50 to 2.71, P < 0.001), and with comorbidities and complications (OR 2.12; 95% CI, 1.61 to 2.89, P < 0.001). Malnutrition is highly prevalent among ARF patients and increases the likelihood of in-hospital death, complications, and use of health care resources.

Acute Kidney Injury↗
PubMed1998

Significance of myocardial ischemic electrocardiographic changes during dipyridamole stress echocardiography.

The aim of this study was to assess the diagnostic and prognostic value of the presence and characteristics of ischemic electrocardiographic (ECG) changes during dipyridamole stress echocardiography. The ECG response in 178 patients with echocardiographic evidence of myocardial ischemia during dipyridamole stress testing was analyzed. ECG changes occurred in 105 patients (59%). Patients with ECG changes had a higher incidence of echocardiographic signs of ischemia at a low dose than patients with an unchanged electrocardiogram (50% vs 23%; p = 0.0002). Three-vessel and/or left main coronary artery disease (CAD) was found in 41% of patients with and in 21% of patients without ECG changes (p = 0.029). During follow-up (33 +/- 19 months), 30 cardiac events occurred: 10 deaths, 6 infarctions, and 14 unstable anginas. Coronary revascularization was performed in 48 patients with and in 17 patients without ECG changes (p = 0.0022). The univariate predictors of cardiac events were: presence of ischemia in > or =4 ECG leads (p = 0.0004), echocardiographic evidence of ischemia at a low dose (p = 0.0062), ST-segment shift on precordial leads (p = 0.0094), family history of CAD (p = 0.0115), coexistence of > or =3 cardiovascular risk factors (p = 0.0156), ST-segment depression (p = 0.0172), and ECG changes during testing (p = 0.0335). At Cox analysis, occurrence of ischemia at a low dose (odds ratio 3.0; 95% confidence interval 1.3 to 6.8) and the presence of ischemia in > or =4 ECG leads (odds ratio 3.5; 95% confidence interval 1.3 to 9.3) had an independent prognostic importance. In conclusion, the presence and characteristics of ischemic ECG changes are associated with more extensive CAD and worse prognostic outlook than are echocardiographic changes alone during dipyridamole stress echocardiography.

Aged↗
PubMed1998

Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor.

The molecular mechanisms by which ovarian hormones stimulate growth of breast tumors are unclear. It has been reported previously that estrogens activate the signal-transducing Src/p21(ras)/Erk pathway in human breast cancer cells via an interaction of estrogen receptor (ER) with c-Src. We now show that progestins stimulate human breast cancer T47D cell proliferation and induce a similar rapid and transient activation of the pathway which, surprisingly, is blocked not only by anti-progestins but also by anti-estrogens. In Cos-7 cells transfected with the B isoform of progesterone receptor (PRB), progestin activation of the MAP kinase pathway depends on co-transfection of ER. A transcriptionally inactive PRB mutant also activates the signaling pathway, demonstrating that this activity is independent of transcriptional effects. PRB does not interact with c-Src but associates via the N-terminal 168 amino acids with ER. This association is required for the signaling pathway activation by progestins. We propose that ER transmits to the Src/p21(ras)/Erk pathway signals received from the agonist-activated PRB. These findings reveal a hitherto unrecognized cross-talk between ovarian hormones which could be crucial for their growth-promoting effects on cancer cells.

Animals↗