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M Falconi

Publications and source records attributed to M Falconi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Does the extent of lymphatic resection affect the outcome in pancreatic cancer?

Radical resection of ductal adenocarcinoma of the pancreas affords the only realistic chance of cure. Despite some reports, in particular from Japan, suggesting an improvement in the long-term prognosis, this is true only in subgroups of selected patients. In actual fact, the overall long-term survival of resected patients is still below 10%. How meaningful is a more extended resection? The lack of randomized prospective trials involving a sufficient number of cases does not enable us to make any final conclusions. The only controlled data, recently reported by an Italian multicenter study, suggested that extended lymphadenectomy improved prognosis not in the whole population of resected patients, but only in a subgroup of patients with lymph node involvement. No definitive judgments can be made without further prospective controlled clinical trials involving a greater number of patients. The suspicion arises that surgery alone, even when extensive, may not be the best treatment for pancreatic ductal cancer.

Adenocarcinoma↗
PubMed1996

Anti-BrdUrd labeling of newly synthesized DNA in HL-60 cells triggered to apoptosis.

Apoptosis is an active process that takes place during pre- and postnatal life. It can be viewed as the essential counterpart to cell proliferation, both phenomena being aimed at the maintenance of tissue and organ homeostasis. Because apoptosis often takes place during the S phase of the cell cycle, we describe the spatial and temporal correlation between DNA synthesis and DNA cleavage taking place in the same nucleus at the same time as a result of the action of camptothecin on proliferating HL-60 cells in vitro. The relationship between DNA synthesis and DNA fragmentation was studied at the single-cell level by bromodeoxyuridine (BrdUrd) incorporation revealed by flow cytometry, electron microscopy, and confocal microscopy. Most HL-60 cells are triggered to apoptosis during the first hour of treatment with camptothecin, and only cells in early-middle S phase are sensitive to the drug effect, whereas late S phase cells appear insensitive to camptothecin-induced apoptosis. Our data, therefore, reinforce the hypothesis of a DNA strand break threshold that may exist in the cell, beyond which the apoptotic program is activated. Moreover, DNA synthesis activity in the nucleus committed to apoptosis is gradually downregulated; after 6 h of camptothecin treatment, virtually no residual DNA replication activity can be detected in micronuclei. DNA repair does not appear to be involved in bromode-oxyuridine incorporation during the apoptotic process.

Antibodies, Monoclonal↗
PubMed1996

Dimer asymmetry in superoxide dismutase studied by molecular dynamics simulation.

Molecular dynamics (MD) simulations of 100 ps have been carried out to study the active-site behaviour of the Cu,Zn superoxide dismutase dimer (SOD) in water. The active site of each subunit was monitored during the whole simulation by calculating the distances between functional residues and the catalytic copper. The results indicate that charge orientation is maintained at each active site but the solvent accessibility varies. Analysis of the MD simulation, carried out by using the atomic displacement covariance matrix, has shown a different intra-subunit correlation pattern for the two monomers and the presence of inter-subunit correlations. The MD simulation presented here indicates an asymmetry in the two active sites and different dynamic behaviour of the two SOD subunits.

Animals↗
PubMed1996

Risk of death from acute pancreatitis. Role of early, simple "routine" data.

CONCLUSIONS: The analysis of all the data available in 192 patients at 24 h from admission shows that only serum glucose above 250 mg/dL (13.88 mmol/L) and serum creatinine above 2 mg/dL (176.8 mumol/L) are prognostic factors of death (P < 0.0001). When, however, pathological chest X-rays are also considered in a subset of 149 patients, these and serum creatinine are prognostic factors of death with odd ratios of 2.9 (95% CL 1.3-6.3) and 9.4 (95% CL 2.2-40.7), respectively (P < 0.0001). BACKGROUND: In patients suffering from acute pancreatitis, neither Ranson scores nor Glasgow criteria evaluation at 24 h yield a sufficiently reliable prognosis of the risk of death from the first acute attack. METHODS: After excluding posttraumatic, postsurgical, and post-ERCP acute pancreatitis, we selected 192 consecutive patients admitted in the first instance to our center for a first attack, distinguishing between patients who died and patients who survived. We used Cox's model to analyze the prognostic weight of variables available within 24 h of admission (sex, age, alcohol intake, smoking habits, 17 biochemical tests, body mass index, chest X-rays, body temperature, and shock status). RESULTS: Seventeen (8.8%) patients died; mortality showed a decreasing trend over the period of years considered and was correlated, among other things, with necrotizing type of pancreatitis, idiopathic etiology, and shock status on admission.

Acute Disease↗
PubMed1996

Pain relapses in the first 10 years of chronic pancreatitis.

PURPOSE: To evaluate whether the annual number of pain relapses of chronic pancreatitis correlated with sex, type of pancreatitis, drinking and smoking, presence of intraductal calcifications, pancreaticojejunostomy, and length of follow-up in the first 10 years of follow-up. METHODS: The authors analyzed 205 nonobstructive chronic pancreatitis cases with at least a 10 year follow-up, for a total of 2,034 person/year observations. Data were recorded on the daily number of cigarettes smoked and grams of alcohol drunk, as well as the presence of intraductal calcifications, and performance of pancreaticojejunostomy. RESULTS: The model for multivariate autoregressive repeated measures analysis indicated that drinking (P < 0.0001), smoking (P < 0.0001), calcifications (P < 0.0001), pancreaticojejunostomy (P < 0.0011), and length of follow-up (P < 0.0001) all correlated significantly with annual number of pain relapses. Pancreaticojejunostomy is probably very effective in reducing pain both physically, by removing the largest intraductal calcifications and obstructions through drainage of Wirsung's duct, and psychologically, by inducing patients to cut down their postsurgical alcohol intake. CONCLUSIONS: Regardless of surgical treatment, patients should be advised to reduce both their alcohol intake and cigarette smoking.

Abdominal Pain↗
PubMed1996

Antagonistic involvement of FIS and H-NS proteins in the transcriptional control of hns expression.

Gel shift and DNase I footprinting experiments showed that Escherichia coli FIS (factor for inversion stimulation) protein binds to at least seven sites in the promoter region of hns. These sites extend from -282 to +25 with two sites, closely flanking the DNA bend located at -150 from the transcriptional startpoint, partly overlapping the H-NS binding sites involved in the transcriptional autorepression of hns. The interplay between FIS, H-NS and the hns promoter region were studied by examining the effects of FIS and H-NS on in vitro transcription of hns-cat fusions, as well as looking at the effect of FIS on preformed complexes containing H-NS and a DNA fragment derived from the hns promoter region. Taken together, our data suggest that in the cell, FIS and H-NS interact with the promoter region of hns and influence their respective interactions (possibly competing for the same binding site), eliciting antagonistic effects so that an interplay between these proteins might contribute to the transcriptional control of hns.

Bacterial Outer Membrane Proteins↗
PubMed1996

Effect of Lys-->Arg mutation on the thermal stability of Cu,Zn superoxide dismutase: influence on the monomer-dimer equilibrium.

The thermal stability of two single (K3R, K67R) and one double (K3R-K67R) mutants of Xenopus laevis B Cu, Zn superoxide dismutase has been studied to test Lys --> Arg substitution as an 'electrostatically conservative' strategy to increase protein stability. The K3R mutant displays an increased thermostability with respect to the wild-type enzyme, whilst a decreased stability was observed in the case of the K67R and K3R-K67R mutants. Concentration dependence of the apparent inactivation constant (kapp) of the latter mutants, as compared to that of the wild type enzyme and K3R mutant, indicates that their higher sensitivity to heat inactivation is due to a perturbation of the dimer association. These results are confirmed also by fluorescence anisotropy measurements of the internal probe Tyr149. The possible role of Arg67 in perturbing the dimer dissociation equilibrium toward the monomeric form is discussed.

Animals↗
PubMed1996

Antimicrobial activity of human pancreatic juice and its interaction with antibiotics.

Pancreatic juice (PJ) should be a factor of variability in the antimicrobial activity of antibiotics eliminated by the pancreas during pancreatic infections. We studied its effects on the activity of antimicrobial drugs with different mechanisms of action. Samples of pure PJ were collected from 16 patients with stabilized external pancreatic fistulas. The antimicrobial activity of the juice at different concentrations (from 1.25 to 100%) alone and in combination with mezlocillin, imipenem, ceftriaxone, gentamicin, ofloxacin, and ciprofloxacin was studied by a microbiological method (continuous turbidimetric recording of bacterial growth). The human PJ showed dose-dependent antimicrobial activity that increased directly with the concentration. The activity of the antibiotics at bactericidal concentrations were not modified by the PJ, while the combination with subinhibitory concentrations produced the following variable and different effects: (i) additivity with mezlocillin, ceftriaxone, gentamicin, and ciprofloxacin and autonomy (no interaction) with imipenem and ofloxacin against Providencia rettgeri and (ii) additivity with ceftriaxone, ofloxacin, gentamicin, imipenem, and mezlocillin and autonomy with ciprofloxacin against Escherichia coli. In the presence of PJ, fluoroquinolones showed constant positive effects, while beta-lactams showed more variable antimicrobial activity. Antibiotic concentrations and PJ pharmacodynamics are the main factors determining the final effect of the interaction in vitro. These results may be useful in choosing antibiotics for the treatment of pancreatic infections when they are supplemented with the pharmacokinetic data for each drug.

Adult↗
PubMed1996

Somatostatin analogues and pancreatic fistulas.

Consideration is given to the characterisation of pancreatic fistulas (PFs), the rationale for their treatment, and supportive and specific treatment measures. Choice of treatment should be based not only on the percentage of closures achieved, but also on their time and cost. The combined use of parenteral nutrition (TPN) and somatostatin inhibits pancreatic secretion well; no therapy can inhibit it completely. Presumptive use of octreotide, a subcutaneous formulation of somatostatin, in patients undergoing elective pancreatic surgery, reduced postoperative complications, mainly PFs, in about 500 patients in two controlled double-blind clinical studies, confirming the use of octreotide both in prophylaxis and treatment. Octreotide has been tested on out-patients after a brief hospitalisation period, at a dose of 100 mg three times a day. Home treatment does not involve co-administration of TPN, thus lowering not only costs but also risks. Optimal doses and the types of fistula amenable to this therapy need to be established and we only use out-patient treatment for chronic low-output fistulas.

Gastrointestinal Agents↗
PubMed1996

Cigarette smoking: an independent risk factor in alcoholic pancreatitis.

It is not known whether cigarette smoking plays a role as a risk factor in alcoholic pancreatitis. The aim of this study was to compare drinking and smoking habits in three groups of male subjects with an alcohol intake in excess of 40 g/day: (i) 67 patients with acute alcoholic pancreatitis, without other known potential causative agents; (ii) 396 patients with chronic alcoholic pancreatitis; and (iii) 265 control subjects randomly selected from the Verona polling lists and submitted to a complete medical checkup. The variables considered were age at onset of disease, years of drinking and smoking, daily alcohol intake in grams, number of cigarettes smoked daily, and body mass index (BMI). Cases differed from controls in daily grams of alcohol, number of cigarettes smoked and BMI (Mann-Whitney U test, p < 0.00001 for each comparison). Multivariate logistic regression analysis, comparing acute and chronic cases, respectively, versus controls, revealed an increased relative risk of pancreatitis in the two comparisons, associated in both cases with a higher alcohol intake (p < 0.00001) and cigarette smoking (p < 0.00001). No significant interaction between alcohol and smoking was noted, indicating that the two risks are independent. In conclusion, in males a higher number of cigarettes smoked daily seems to be a distinct risk factor in acute and chronic alcoholic pancreatitis.

Adult↗
PubMed1995

Effectiveness of gabexate mesilate in acute pancreatitis. A metaanalysis.

Since the effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial, a metaanalysis of the published literature was conducted to address this problem. Five randomized trials were identified by our literature search. Three end points (mortality, complications, and complications requiring surgery) were evaluated. The results of our metaanalysis indicate that the treatment with gabexate mesilate does not affect mortality at 90 days (P = 0.27), but significantly reduces the incidence of complications requiring surgery (odds ratio = 0.61, 95% CI: 0.41-0.89; P < 0.05) and of complications in general (odds ratio = 0.69, 95% CI: 0.54-0.89; P < 0.05). Because the drug proves to be beneficial only to a low proportion of the treated patients, its clinical impact seems to be small. A pharmacoeconomic evaluation shows that its use in all patients with acute pancreatitis would imply a very high cost for preventing each complication. The administration of the drug to select patients who are at higher risk of complications could have a better cost-effectiveness ratio. However, specific studies on this point are still lacking.

Acute Disease↗
PubMed1995

High-resolution FEISEM detection of DNA centromeric probes in HeLa metaphase chromosomes.

HeLa metaphase chromosome spreads were hybridized with centromeric biotinylated DNA probes and detected with gold-conjugated anti-biotin antibodies. Chromosomes were observed by an in-lens field emission scanning electron microscope (FEISEM), which permits detection of biological samples without any coating. DNA probes were well localized in the centromeric region of chromosomes and there was clear discrimination between 10 nm fibers that hybridized to DNA probes and those that did not hybridize. This approach shows that in situ hybridization can be directly visualized at the FEISEM level by evaluating only secondary electron emission, which allows physical localization of the hybridized probe with high resolution so that backscatter detection represents only a control. Because chromosomes maintain the 10-nm fiber organization after in situ hybridization procedures, our data suggest that this fiber represents the lowest order of chromatin arrangement that permits transitory DNA denaturation.

Centromere↗
PubMed1995

[Closed surgical treatment in acute severe pancreatitis].

Between 1976 and 1994, 318 patients underwent surgical closed retro-endoperitoneal drainage and post-operative lavage for acute necrotizing severe pancreatitis. The main indication was sepsis (66.4%). The ratio between operated on and the overall number of observed patients has been progressively shifting towards medical treatment. Furthermore in the operated group the timing of surgery has been delayed step by step. The Authors discuss improvements in the understanding of the etiological and therapeutical aspects of the disease which has had a better outcome in recent years, survival rate of 91.4%. The personal option for the closed surgical approach is based on the progressive improvement of the technique and on the good results obtained both in terms of mortality and associated morbidity; as regards the latter problem the open techniques seems to be related to a higher complication rate than the closed one.

Acute Disease↗
PubMed1994

Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group.

A placebo-controlled double-blind multicentre study, with randomization into parallel groups, was performed to determine whether perioperative subcutaneous administration of octreotide 0.1 mg every 8 h reduces the rate of complications specifically related to pancreatic surgery. In all, 252 patients were evaluated (153 men, 99 women; mean(s.e.m.) age 53.1(0.8) years) who had pancreatic or periampullary tumour or other duodenal disease (157 patients) or chronic pancreatitis (95) and were undergoing elective pancreatic resection (100 Whipple's procedure, 60 distal resection, 12 others), pancreaticojejunostomy (66) or enucleation of pancreatic lesions (14). The proportion of patients with complications was significantly lower in the group treated with octreotide than in the placebo group (15.6 versus 29.2 per cent, P = 0.01). Octreotide thus appears to reduce substantially the risk of complications related to elective pancreatic surgery. Moreover, treatment acceptability was high.

Administration, Cutaneous↗
PubMed1994

Molecular modeling and electrostatic potential calculations on chemically modified Cu,Zn superoxide dismutases from Bos taurus and shark Prionace glauca: role of Lys134 in electrostatically steering the substrate to the active site.

The three-dimensional structure of Cu,Zn superoxide dismutase (SOD) from the shark Prionace glauca was homology modeled on the structure of the bovine enzyme used as a template. Shark SOD displays the conservative substitution of one of the residues involved in the electrostatic guidance of superoxide toward the active site of the enzyme, i.e., Lys134, which is replaced by arginine. The association rate, calculated by brownian dynamics simulations incorporating electrostatic terms, and the enzyme reaction rate, measured by the pulse radiolysis method, were found to be identical for both bovine and shark SODs. In order to quantify the role of Lys134 in electrostatically steering the superoxide to the active site, chemical modification of the lysine residues by carbamoylation was carried out on both bovine and shark SODs. Experimental determination of the enzymatic reaction rate indicated that the charge located on the residue 134 gives 19% contribution to the guidance of superoxide anion at low ionic strength. This value matches the association rates predicted by brownian dynamics.

Amino Acid Sequence↗
PubMed1994

High resolution detection of uncoated metaphase chromosomes by means of field emission scanning electron microscopy.

HeLa metaphase chromosomes were examined by means of "in lens" field emission scanning electron microscopy, which permits high resolution detection of uncoated biological samples. By using uncoated chromosomes as a model for comparison we report evidence of how traditional scanning electron microscopy techniques such as metal coating and conductive methods can generate errors in chromosome structure evaluation, since both give rise to morphological artifacts. By comparing the morphology of uncoated chromosomes obtained by two different isolation procedures, such as that utilized in standard cytogenetics and the polyamine method, we have drawn the following conclusions: (a) the standard cytogenetic method gives rise to a chromosome structure consisting of a flattened network of 10 nm fibers, in which higher order chromatin organization is absent. (b) Chromosomes obtained by the polyamine method show both three-dimensional profile and higher level folding of chromatin fibers, supporting the loop chromosome organization previously suggested by scanning electron microscopy observation of hexylene glycol isolated chromosomes.

Chromosomes, Human↗
PubMed1994

Behavior of antibiotics during human necrotizing pancreatitis.

The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic samples were collected simultaneously at different time intervals after parenteral drug administration by computed tomography-guided needle aspiration, intraoperatively, and from surgical drainages placed during surgery. Drug concentrations were determined by microbiological and high-performance liquid chromatography assays. All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%) and metronidazole (99%). The concentrations of pefloxacin (13.0 to 23 micrograms/g) and metronidazole (8.4 micrograms/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 micrograms/g) and mezlocillin (8.0 and 15.0 micrograms/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 microgram/g) were inadequate. Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue. The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.

Adult↗