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Showing papers by "University of Milan published in 1995"


Journal ArticleDOI
TL;DR: Whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index.
Abstract: Background Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal levels may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. Methods A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). Results The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P<0.001). Mortality was 48.4, ...

1,365 citations


Journal ArticleDOI
13 Apr 1995-Nature
TL;DR: In this article, a synergistic effect between A beta and interferon-gamma was found to trigger the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia.
Abstract: Alzheimer's disease is the most common cause of progressive intellectual failure. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of beta-amyloid protein (A beta), infiltrated by reactive microglia and astrocytes. Although A beta, and a portion of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct toxic effect on neurons, the role of microglia in such neuronal injury remains unclear. Here we report a synergistic effect between A beta and interferon-gamma (IFN-gamma) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-gamma and A beta leads to neuronal cell injury in vitro. These findings suggest that A beta and IFN-gamma activate microglia to produce reactive nitrogen intermediates and TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.

1,337 citations



Journal ArticleDOI
TL;DR: Evidence is given that multivariate models--which allow evaluation of the interactions between changes in blood pressure, heart rate, and other biological signals in the time or frequency domains--offer a more comprehensive approach to the assessment of cardiovascular regulation than that represented by the separate analysis of fluctuations inBlood pressure or heart rate only.
Abstract: Blood pressure variability includes rhythmic and nonrhythmic fluctuations that, with the use of spectral analysis, appear as clear peaks or broadband power, respectively. This review offer...

864 citations


Journal ArticleDOI
TL;DR: This is the first study to demonstrate differential responses of LQTS patients to interventions targeted to their specific genetic defect, and it is suggested that LQT3 patients may be more likely to benefit from Na+ channel blockers and from cardiac pacing because they would be at higher risk of arrhythmia at slow heart rates.
Abstract: Background The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene. These findings opened the possibility of attempting gene-specific control of ventricular repolarization. We tested the hypothesis that the QT interval would shorten more in LQT3 than in LQT2 patients in response to mexiletine and also in response to increases in heart rate. Methods and Results Fifteen LQTS patients were studied. Six LQT3 and 7 LQT2 patients were treated with mexiletine, and its effects on QT and QTc were measured. Mexiletine significantly shortened the QT interval among LQT3 patients (QTc from 535±32 to 445±31 ms, P<.005) but not among LQT2 patients (QTc from 530±79 to 503±60 ms, P=NS). LQT3 patients (n=7) shortened their QT interval in response to increases in heart rate much more than LQT2 patients (n=4) and also more than 18 healthy control subjects (9.45±3.3 versus 3.95±1.97 and 2.83±1.33, P<.05; data e...

775 citations


Journal ArticleDOI
TL;DR: This work presents a novel, scalable, scalable and scalable approach that can be applied to the rapidly changing and rapidly changing landscape of gastroenterological care.

725 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated whether these alterations involve sympathetic drive in 10 young obese sub-groups and found that the sympathetic drive was not involved in the majority of the cases.
Abstract: Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subj...

597 citations


Journal ArticleDOI
TL;DR: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG, providing insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.
Abstract: Background The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. Methods and Results Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the absolute height of the T wave (Tamplitude, in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n=47), 7 (n=30), and 11 (n=76). Genotypic data were used to define each family member as being affected or unaffected with long QT syndrome. Affected member...

593 citations


Journal ArticleDOI
TL;DR: Data from a large and unbiased sample of a general population show that home and 24 h or daytime average blood pressures are much lower than clinic blood pressure.
Abstract: Objective : To determine ambulatory and home blood pressure means and distributions in relation to clinic blood pressure in a general population. Methods : We obtained a random sample of 2400 subjects stratified by sex and 10 year age groups to be representative of residents aged 25-64 years of the city of Monza. Participation rate was 69% (1651 subjects). Blood pressure measurements consisted of clinic blood pressure (average of three measurements, sphygmomanometry), home blood pressure (average of morning and evening measurements, semiautomatic device) and ambulatory blood pressure (automatic readings at 20min intervals, Spacelabs 90207). Clinic blood pressure was obtained both before and after home and ambulatory blood pressures. Data analysis did not include 213 subjects receiving antihypertensive drug treatment and was therefore limited to 1438 participants. Results : In the 1438 subjects, clinic, home and ambulatory blood pressure showed a normal-like distribution, with a taller peak and a narrower base for ambulatory than for home and clinic values. Clinic, home and ambulatory blood pressures were significantly related to each other (P always <0.001). ). The means of the two clinic blood pressures obtained on consecutive days were superimposable (127.4 ± 17.0/82.3 ± 9.8 and 128.2 ± 16.5/81.9 ± 9.9 mmHg) and both were markedly higher than home and 24 h average blood pressures (8.2 mmHg), which were similar to one another. The differences between clinic and home or 24 h average blood pressure were similar in both sexes but increased with increasing age and clinic blood pressure values. The influence of clinic blood pressure values on the clinic-ambulatory or clinic-home blood pressure differences was more important than age. Although higher than the 24 h average value, daytime average blood pressure was also lower than clinic blood pressure. Night-time blood pressure was markedly lower than the daytime value in both sexes and at all ages. Conclusion : Data from a large and unbiased sample of a general population show that home and 24 h or daytime average blood pressures are much lower than clinic blood pressure. The relatively close correlation between blood pressure values measured with the different methods used has allowed calculation of home and ambulatory blood pressure values corresponding to the accepted upper limit of normality of clinic blood pressure (140/90 mmHg). The upper limit of normality for the population was for both home and ambulatory blood pressures in the range 120-130 and 75-81 mmHg for systolic and diastolic values, respectively, with slight differences depending on sex and age. Taking 140/90 mmHg as the upper normal limit of the population is therefore an error that leads to individuals whose home or ambulatory blood pressures are high being considered as normotensive.

579 citations


Journal ArticleDOI
TL;DR: The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS) and found that with increasing PEEP, the VTct distribution decreased significantly in the upper levels, did not change in the middle levels, and increased significantly (p < 0.01) in the lower levels.
Abstract: The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS). A CT section was obtained in the supine position at 0, 5, 10, 15, and 20 cm H2O positive end-expiratory pressure (PEEP) and at the corresponding inspiratory plateau pressure (21 +/- 1.8, 26 +/- 1.4, 31 +/- 1.8, 38 +/- 2.1, and 46 +/- 3.2 cm H2O [mean +/- SE]), keeping VT constant. Each CT section was divided along its ventral-dorsal height into 10 equally spaced intervals (levels). Vi(insp) and Vi(exp) were defined as the gas volume for level i (i = 1 to 10) at end-inspiration and at end-expiration, respectively. The following variables were computed at each lung level: (1) distribution of CT section tidal volume (VTct), i.e., the fraction of VT that inflates a given lung level; (2) the plateau-induced and PEEP-induced recruitment, i.e., the amount of lung tissue previously collapsed that inflates at plateau pressu...

524 citations


Journal ArticleDOI
TL;DR: In this paper, a survey about Hyers-Ulam stability of functional equations and systems in several variables is presented, with a focus on the stability of the Ulam model.
Abstract: The paper is a survey about Hyers—Ulam stability of functional equations and systems in several variables.

Journal ArticleDOI
TL;DR: In this article, measures of technical and scale efficiencies are derived in the Italian banking industries by implementing non-parametric Data Envelopment Analysis on a cross section of 174 Italian banks taken in 1991.
Abstract: Measures of technical and scale efficiencies are derived in the Italian banking industries by implementing non-parametric Data Envelopment Analysis on a cross section of 174 Italian banks taken in 1991. The methodology of the parametric and non-parametric approaches to measure efficiency are discussed. The existence of both technical and allocative efficiency is established. This result is robust to modifications in the specification of inputs and outputs suggested by the Intermediation Approach and by the Asset Approach. In implementing both the Intermediation and the Asset Approach the traditional specification of inputs is modified to allow an explicit role for financial capital. In addition, regression analysis is used on a bank-specific measure of inefficiency to investigate determinants of banks' efficiency. Efficiency is best explained by productive specialization, size and, to a lesser extent, by location.

Journal ArticleDOI
TL;DR: Routine HCV screening is not recommended in pregnant women because of a lack of evidence to suggest an increased risk of HCV transmission through breast feeding and drugs to treat established infections in mothers and infants.

Journal ArticleDOI
TL;DR: The data suggest that natural antioxidants could play a role in inhibiting the formation of cytotoxic products such as lipid peroxides thus retarding the onset of the atherosclerotic damage.

Journal ArticleDOI
TL;DR: The results are the first evidence that components of the phenolic fraction of olive oil can inhibit platelet function and eicosanoid formation in vitro, and that other, partially characterized, olive derivatives share these biological activities.

Journal ArticleDOI
TL;DR: It is confirmed that there are alterations in the NAWM of MS patients and it is suggested that such changes might be relevant to the disability in MS.
Abstract: We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.

Journal Article
TL;DR: The results suggest that the antiaggregating activity of resveratrol is related to its concentration in wine.
Abstract: The antiaggregating effect of the phytoalexin resveratrol (3,4,5-trihydroxystilbene), alone or associated with red wine, and polyphenol have been evaluated in vitro at different concentrations on platelet-rich plasma from healthy volunteers Resveratrol at the concentration of 356 micrograms/l was able to lower platelet aggregation by 503% +/- 183 Red wine containing 12 mg/l of natural trans-resveratrol and 36 milligrams of polyphenols diluted 1000-fold (final resveratrol concentration: 12 micrograms/l) inhibited platelet aggregation by 419% +/- 211 By adding resveratrol to the wine up to a concentration of 12 micrograms/l, inhibition was raised to 785% +/- 470 These results suggest that the antiaggregating activity of resveratrol is related to its concentration in wine

Journal ArticleDOI
TL;DR: The results of a two-stage genome-wide search for genes conferring susceptibility to schizophrenia were reported in this article. But none of these genes have been found to be associated with the HLA region on chromosome 6p.
Abstract: Schizophrenia is thought to be a multifactorial disease with complex mode of inheritance. Using a two-stage strategy for another complex disorder, a number of putative IDDM-susceptibility genes have recently been mapped. We now report the results of a two-stage genome-wide search for genes conferring susceptibility to schizophrenia. In stage I, model-free linkage analyses of large pedigrees from Iceland, a geographical isolate, revealed 26 loci suggestive of linkage. In stage II, ten of these were followed-up in a second international collaborative study comprising families from Austria, Canada, Germany, Italy, Scotland, Sweden, Taiwan and the United States. Potential linkage findings of stage I on chromosomes 6p, 9 and 20 were observed again in the second sample. Furthermore, in a third sample from China, fine mapping of the 6p region by association studies also showed evidence for linkage or linkage disequilibrium. Combining our results with other recent findings revealed significant evidence for linkage to an area distal of the HLA region on chromosome 6p. However, in a fourth sample from Europe, the 6p fine mapping finding observed in the Chinese sample could not be replicated. Finally, evidence suggestive of locus heterogeneity and oligogenic transmission in schizophrenia was obtained.

Journal ArticleDOI
TL;DR: It is suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance.
Abstract: A direct influence of dietary long-chain polyunsaturated fatty acids (LC-PUFA) on the developmental quotient (DQ) of the healthy term infant remains unexplored. To test this hypothesis, we designed a prospective study of three types of diet. Twenty-nine infants received a LC-PUFA-supplemented formula, 31 received a standard infant formula, and 30 infants were breast-fed exclusively. Neurodevelopmental response was measured by the Brunet-Lezine psychomotor development test at 4 mo. The fatty acid status was also assessed among three diet subgroups (59 subjects) at 4 mo. Formula-fed infants who received LC-PUFA supplementation scored significantly higher (p < 0.01) on the Brunet-Lezine scale than infants who received the standard formula. Breast-fed infants also performed better than those fed the standard formula. Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula. These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance.

Journal ArticleDOI
TL;DR: It is shown that ferritin synthesis is significantly stimulated in the liver of rats subjected to oxidative stress by treatment with phorone, a glutathione-depleting drug, and direct measurements of intracellular free iron levels by EPR indicate that the increased ferritIn synthesis can be mediated by an expansion of the free iron pool.

Journal ArticleDOI
TL;DR: The presence of palmitate appears to play a key role in the membrane localization of either the entirepolypeptide or parts of it, and may regulate the interactions of these polypeptides with other proteins.

Journal ArticleDOI
TL;DR: To investigate the existence of an association between the frequency of chromosome aberrations in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy.

Journal ArticleDOI
TL;DR: Observations suggest the existence of a new pathway of trans-synaptic regulation of gene expression in mice derived from older pups, which appears to be developmentally regulated.
Abstract: Neuronal proliferation, migration, and differentiation are regulated by the sequential expression of particular genes at specific stages of development. Such processes rely on differential gene expression modulated through second-messenger systems. Early postnatal mouse cerebellar granule cells migrate into the internal granular layer and acquire differentiated properties. The neurotransmitter glutamate has been shown to play an important role in this developmental process. We show here by immunohistochemistry that the RelA subunit of the transcription factor NF-kappa B is present in several areas of the mouse brain. Moreover, immunofluorescence microscopy and electrophoretic mobility-shift assay demonstrate that in cerebellar granule cell cultures derived from 3- to 7-day-old mice, glutamate specifically activates the transcription factor NF-kappa B, as shown by binding of nuclear extract proteins to a synthetic oligonucleotide reproducing the kappa B site of human immunodeficiency virus. The use of different antagonists of the glutamate recpetors indicates that the effect of glutamate occurs mainly via N-methyl-D-aspartate (NMDA)-receptor activation, possibly as a result of an increase in intracellular Ca2+. The synaptic specificity of the effect is strongly suggested by the observation that glutamate failed to activate NF-kappa B in astrocytes, while cytokines, such as interleukin 1 alpha and tumor necrosis factor alpha, did so. The effect of glutamate appears to be developmentally regulated. Indeed, NF-kappa B is found in an inducible form in the cytoplasm of neurons of 3- to 7-day-old mice but is constitutively activated in the nuclei of neurons derived from older pups (8-10 days postnatal). Overall, these observations suggest the existence of a new pathway of trans-synaptic regulation of gene expression.

Journal ArticleDOI
TL;DR: In vivo evidence is provided for a fractionation of the neural substrates of semantic knowledge in man using positron emission tomography during the recognition of visual stimuli representing living and nonliving entities.
Abstract: Using positron emission tomography, we mapped brain activity in normal volunteers during the recognition of visual stimuli representing living (animals) and nonliving (artefacts) entities. The subjects had to decide whether pairs of visual stimuli were different representations of the same object, o

Journal ArticleDOI
01 Jan 1995-Surgery
TL;DR: Octreotide was able to reduce significantly the incidence of pancreatic fistula after elective pancreatic resections, and when specific pancreatic complications were grouped together and evaluated, they occurred less frequently in the treated group than in the placebo group.

Journal ArticleDOI
TL;DR: Surgery and percutaneous ethanol injection improve survival in single hepatocellular carcinoma associated with Child A and B cirrhosis compared to untreated patients in the same Child class.

Journal ArticleDOI
TL;DR: The results suggest that alpha-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.
Abstract: alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of alpha-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and alpha-MSH production in RAW 264.7 cultured murine macrophages stimulated with bacterial lipopolysaccharide and interferon gamma. alpha-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. alpha-MSH increased cAMP accumulation in RAW cells, characteristic of alpha-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary alpha-MSH receptor (melanocortin 1). mRNA for proopiomelanocortin, the precursor molecular of alpha-MSH, was expressed in RAW cells, and tumor necrosis factor alpha increased production and release of alpha-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor alpha can induce macrophages to increase production of alpha-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of NO. The results suggest that alpha-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.

Journal ArticleDOI
TL;DR: This work introduces finitely additive measures (called states) on MV algebras with the intent of capturing the notion of ‘average degree of truth’ of a proposition.
Abstract: Chang's MV algebras are the algebras of the infinite-valued sentential calculus of Łukasiewicz. We introduce finitely additive measures (called states) on MV algebras with the intent of capturing the notion of ‘average degree of truth’ of a proposition. Since Boolean algebras coincide with idempotent MV algebras, states yield a generalization of finitely additive measures. Since MV algebras stand to Boolean algebras as AFC*-algebras stand to commutative AFC*-algebras, states are naturally related to noncommutativeC*-algebraic measures.


Journal Article
TL;DR: The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis and microvessel quantitation, however, MVD does not provide significant prognostic information in colOREctal cancer patients.
Abstract: Angiogenesis is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of prognostic value in several types of malignancies. Scarce data are available on angiogenesis in gastrointestinal tumors. We studied 36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation. Endothelial cells were immunostained with an anti-CD31 mAb; in each case three microscopic fields (x 200) with the highest number of microvessels were counted: the average value of the three fields was used to evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41 cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001; adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with metastases, disease stage, and patient survival. The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis. MVD, however, does not provide significant prognostic information in colorectal cancer patients.