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Biomedical subjects

M Falconi

Publications and source records attributed to M Falconi.

At least 91 records · Page 5Linked to original sources
PubMed2000

A single-institution experience with fistulojejunostomy for external pancreatic fistulas.

External pancreatic fistulas resistant to medical treatment are an indication for surgery. Over the period from May 1986 to March 1999, we operated on 17 patients suffering from a stabilized external pancreatic fistula as a result of surgical treatment for severe acute pancreatitis in 12 cases, chronic pancreatitis in 3, duodenopancreatectomy in 1, and islet cell tumor enucleation in 1. The surgical repair consisted of precise identification of the fistula tract around the drainage tube and its anastomosis with a Roux-en-Y jejunal loop (fistulojejunostomy). The surgical mortality was nil, and the postoperative outcome was uneventful in 12 patients. Four patients experienced surgical complications, all of which were treated conservatively. After a median follow-up of 93 months, 14 patients are still alive and healthy, 1 had died of neoplastic cachexia, and 2 were lost to follow-up. In our experience, fistulojejunostomy appears to be safe, easy to perform, and curative.

Acute Disease↗
PubMed2000

Changes in pancreatic resection for chronic pancreatitis over 28 years in a single institution.

BACKGROUND: Because of advances in knowledge over recent years there is reason to believe that surgical attitudes towards patients with chronic pancreatitis may have changed. METHODS: Some 547 patients were treated surgically for chronic pancreatitis from 1971 to June 1998. Anastomoses were performed in 80 per cent (438 patients) and resections in 20 per cent (109 patients). Indications and type of operation were analysed, as were mortality and morbidity rates and long-term follow-up results, in patients undergoing resection both over the period as a whole and after dividing the series into two subperiods of 14 years. RESULTS: In the second 14-year period, there was a significant reduction in the percentage of resections compared with anastomoses (28 per cent (69 of 244 patients) versus 13 per cent (40 of 303); P < 0.0001), and a significant change in the type of resection with a substantial increase in resections of the head compared with those of the body and tail. Statistically significant reductions occurred in operating times, number of units of blood transfused (mean(s.d.) 4.7(3.6) versus 1.2(1.6) units; P = 0.0001) and mean hospital stay (18 versus 14 days for pylorus-preserving and 12 versus 8 days for left pancreatectomy with splenectomy; P < 0. 01); mortality and morbidity rates also tended to decrease, but not significantly. CONCLUSION: A different pattern has emerged over the years as regards both the type and number of resections performed.

Adolescent↗
PubMed2000

Alcohol intake, cigarette smoking, and body mass index in patients with alcohol-associated pancreatitis.

The differential diagnosis between acute and chronic alcohol-associated pancreatitis is often difficult or impossible at onset of the disease. A study was conducted to determine possible relationships between patients suffering from a first episode of acute alcoholic pancreatitis and patients with unequivocal chronic alcoholic pancreatitis, comparing age, drinking and smoking habits, and body mass index (BMI). Two groups of men were considered. The first group consisted of 67 patients with a diagnosis of acute alcohol-associated pancreatitis in the absence of other potential pathogenic factors; in this group, 48 of the 56 patients surviving the acute attack were submitted to imaging studies for a median period of 9 years. The second group consisted of 396 patients with chronic alcoholic pancreatitis with a median follow-up period of 12 years. The variables that differed significantly in the two groups were BMI (p < 0.009) and number of smokers (p < 0.001). Logistic regression analysis selected only BMI with an odds ratio of 1.19 (95% CI, 1.07-1.33; p < 0.00015) in favor of acute alcoholic pancreatitis. In male patients, from an epidemiologic standpoint, only smoking habits and BMI are significant differences at clinical onset between the two types of pancreatitis.

Acute Disease↗
PubMed2000

Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis.

BACKGROUND: Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. AIM: To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. METHODS: We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. RESULTS: Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis. CONCLUSIONS: Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.

Adult↗
PubMed1999

Molecular dynamics simulations of Cu,Zn superoxide dismutase: effect of temperature on dimer asymmetry.

Molecular dynamics simulations of solvated dimeric Cu,Zn superoxide dismutase have been carried out at four temperatures, namely 200, 225, 250 and 300 K. Analysis of the backbone-to-backbone hydrogen bonds number indicates that the symmetry observed in the two subunits at 200 K is gradually lost by heating the system. The C(alpha) atoms displacement cross-correlation maps confirm that the asymmetric behaviour of the two subunits increases as a function of temperature. The dynamic cross-correlation of the subunits volumes indicates a fast correlation between the two subunits at 300 K, which is delayed upon lowering the simulation temperature. These results indicate that temperature plays an essential role in injecting such an asymmetry; the two subunits being asymmetric and in rapid communication at 300 K, and almost symmetric and in slow communication at lower temperatures.

Journal Article↗
PubMed1999

A model for the incorporation of metal from the copper chaperone CCS into Cu,Zn superoxide dismutase.

BACKGROUND: Recent studies have identified the human copper chaperone CCS as the presumed factor responsible for copper incorporation into superoxide dismutase (SOD). A lack of knowledge of the chaperone's three-dimensional structure has prevented understanding of how the copper might be transferred. RESULTS: The three-dimensional structure of CCS was homology modelled using the periplasmic protein from the bacterial mercury-detoxification system and the structure of one subunit of the human SOD dimeric enzyme as templates. On the basis of the three-dimensional model, a mechanism for the transfer of copper from CCS to SOD is proposed that accounts for electrostatic acceptor recognition, copper storage and copper-transfer properties. CONCLUSIONS: The proposed model identifies a path for copper transfer based on the presence of different metal sites characterized by sulphur ligands. Such a model permits the development of strategies able to interfere with copper incorporation in SOD, providing a possible way to prevent or arrest degeneration in the fatal motor neuron disorder amyotrophic lateral sclerosis.

Amino Acid Sequence↗
PubMed1999

Evolutionary constraints for dimer formation in prokaryotic Cu,Zn superoxide dismutase.

Prokaryotic Cu,Zn superoxide dismutases are characterized by a distinct quaternary structure, as compared to that of the homologous eukaryotic enzymes. Here we report a newly determined crystal structure of the dimeric Cu,Zn superoxide dismutase from Photobacterium leiognathi (crystallized in space group R32, refined at 2.5 A resolution, R-factor 0.19) and analyse it in comparison with that of the monomeric enzyme from Escherichia coli. The dimeric assembly, observed also in a previously studied monoclinic crystal form of P. leiognathi Cu,Zn superoxide dismutase, is based on a ring-shaped subunit contact region, defining a solvated interface cavity. Three clusters of neighbouring residues play a direct role in the stabilization of the quaternary assembly. The present analysis, extended to the amino acid sequences of the other 11 known prokaryotic Cu,Zn superoxide dismutases, shows that at least in five other prokaryotic enzymes the interface residue clusters are under strong evolutionary constraint, suggesting the attainment of a quaternary structure coincident with that of P. leiognathi Cu,Zn superoxide dismutase. Calculation of electrostatic fields for both the enzymes from E. coli and P. leiognathi shows that the monomeric/dimeric association behaviour displayed by prokaryotic Cu, Zn superoxide dismutases is related to the distribution of surface charged residues. Moreover, Brownian dynamics simulations reproduce closely the observed enzyme:substrate association rates, highlighting the role of the active site neighbouring residues in determining the dismutase catalytic properties.

Amino Acid Sequence↗
PubMed1999

Functional modulation of the Thr72-->Ile mutant from Scapharca inaequivalvis homodimeric hemoglobin.

The pH and temperature dependence of both the kinetic and thermodynamic properties of the Thr72-->Ile mutant of Scapharca inaequivalvis homodimeric hemoglobin were investigated between pH 2 and 10 and between 8 degrees C and 36 degrees C, in comparison with the wild-type recombinant protein. Results demonstrate pH-independent O2-binding properties, at least between pH 5 and 10, with the higher affinity of the mutant being related to a less negative entropy change. This observation may relate to a variation in the number of water molecules involved in the intersubunit communication. Furthermore, the kinetic properties of ligand association and dissociation seem to be in keeping with possible structural alterations of water molecules at the subunit interface occurring in the Thr72-->Ile mutant as well as with amino acid residues involved in the modulation of reactivity and cooperativity at the level of (1) the proximal side of the heme pocket and of (2) the heme propionates bridging the two subunits.

Amino Acid Substitution↗
PubMed1999

Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer.

The aim of this study was to compare alcohol and smoking as risk factors in the development of chronic pancreatitis and pancreatic cancer. We considered only male subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47 extrapancreatic cancers; (2) 69 patients with histologically well documented pancreatic cancer and no clinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona polling list and submitted to a complete medical check-up. Chronic pancreatitis subjects drink more than control subjects and more than subjects with pancreatic cancer without chronic pancreatitis (P<0.001). The percentage of smokers in the group with chronic pancreatitis is significantly higher than that in the control group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P<0.001] and in the group with pancreatic carcinomas but with no history of chronic pancreatitis (OR 5.3; 95% CI 3.0-9.4; P<0.001). In conclusion, our study shows that: (1) the risk of chronic pancreatitis correlates both with alcohol intake and with cigarette smoking with a trend indicating that the risk increases with increased alcohol intake and cigarette consumption; (2) alcohol and smoking are statistically independent risk factors for chronic pancreatitis; and (3) the risk of pancreatic cancer correlates positively with cigarette smoking but not with drinking.

Adenocarcinoma↗
PubMed1999

Incidence of cancer in the course of chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis patients appear to present an increased incidence of pancreatic cancer. The aim of the study was to compare the incidence of cancer, whether pancreatic or extrapancreatic, in our chronic pancreatitis cases with that in the population of our region. METHODS: We analyzed 715 cases of chronic pancreatitis with a median follow-up of 10 yr (7287 person-years); during this observation period they developed 61 neoplasms, 14 of which were pancreatic cancers. The cancer incidence rates were compared, after correction for age and gender, with those of a tumour registry. RESULTS: We documented a significant increase in incidence of both extrapancreatic (Standardized Incidence Ratio [SIR], 1.5; 95% confidence interval [CI], 1.1-2.0; p <0.003) and pancreatic cancer (SIR, 18.5; 95% CI, 10-30; p <0.0001) in chronic pancreatitis patients. Even when excluding from the analysis the four cases of pancreatic cancer that occurred within 4 yr of clinical onset of chronic pancreatitis, the SIR is 13.3 (95% CI, 6.4-24.5; p <0.0001). If we exclude these early-onset cancers, there would appear to be no increased risk of pancreatic cancer in nonsmokers, whereas in smokers this risk increases 15.6-fold. CONCLUSIONS: The risks of pancreatic and nonpancreatic cancers are increased in the course of chronic pancreatitis, the former being significantly higher than the latter. The very high incidence of pancreatic cancer in smokers probably suggests that, in addition to cigarette smoking, some other factor linked to chronic inflammation of the pancreas may be responsible for the increased risk.

Adult↗
PubMed1999

Role of chemoembolization in synchronous liver metastases from pancreatic endocrine tumours.

Endocrine tumours of the pancreas, even in case of liver involvement, are generally characterized by a slower evolution and a better prognosis, if compared with ductal carcinoma. This fact gives reason to a radical surgical approach, whenever possible, and to the research of any effective adjuvant treatment. For this purpose, hepatic transarterial chemoembolization (TACE) has been proposed in recent years for the treatment of metastatic endocrine tumours. Out of 80 patients suffering from endocrine tumours of the pancreas, observed between January 1985 and December 1996, 28 (35%) presented liver metastases at the time of diagnosis. Twelve of these patients were submitted to palliative resection of pancreatic tumour and one or more cycles of TACE. Overall survival was 50% (6/12); median survival was 35.4 months (range 4-75). These results suggest that chemoembolization, combined with surgical resection of primary malignancy, appears to be able to control the disease for a certain time and to increase the survival rate.

Actuarial Analysis↗
PubMed1999

Assessment and treatment of severe pancreatitis. Protease inhibitor.

From the theoretical point of view, antiproteolytic therapy would seem to be the rationale for acute pancreatitis management. Unfortunately, clinical human trials studying the role of antiproteases in the treatment of acute pancreatitis differ in several respects in terms of their basic design. As a consequence, any form of homogeneous analysis of the reported data as a whole is impossible. Considering the data emerging from a meta-analysis of five trials a rational use of antiproteases may result in a reduction of complications requiring surgery and of patient management costs only in selected cases, meaning by that severe and necrotic forms. As regards presumptive applications, over 400 patients were prospectively tested versus placebo in a double-blind trial with the aim of preventing acute pancreatitis after ERCP. The complication incidence was significantly lower among the pretreated patients; anyway, also in this field of protease inhibitor clinical application it is necessary to identify the patients with the greatest risk to develop post-ERCP acute pancreatitis. In conclusion, antiproteases can still play a role when given prophylactically or when used in the very early phases of the disease; moreover a 'multiple drugs approach' (including, for example, suitable antibiotics) seems to represent nowadays the most modern and rational treatment of acute pancreatitis.

Health Care Costs↗
PubMed1999

Management of digestive tract fistulas. A review.

Digestive tract fistulas are a complex subject in terms both of classification and management. There is still a lack of firm epidemiological data regarding the their incidence, though the prognostic factors conditioning the prognosis of these patients are now well known. They are related mainly to the nutritional status of the patients and to the presence or otherwise of sepsis. Instrumental investigations should be aimed not merely at identifying the complication, but also at guiding clinicians in their choice of therapeutic management. According to the various situations arising, the treatment will be surgical, endoscopic or conservative medical. In the latter case, the clinician should establish first of all whether, as a result of the site of the fistula or the nutritional status, the patient requires total parenteral or enteral artificial nutrition, whenever possible. In those cases in which parenteral nutrition is indicated, the ideal drug with the best proven ability to shorten healing times and reduce the number of complications when used in combination with parenteral nutrition is naturally occurring somatostatin at the dose of 250 micrograms/h over 24 h. In all other cases, if the fistula is clinically important, its synthetic analogue, octreotide, should be the drug of choice and can be administered subcutaneously. The amount of octreotide administered ranges from 300 to 600 micrograms/day in 3 or 4 daily doses.

Digestive System Fistula↗
PubMed1999

Scanning electron microscopic detection of nuclear structures involved in DNA replication.

In order to evaluate at the ultrastructural level the three dimensional chromatin arrangement during interphase and particularly during the S phase, the immunogold detection of Bromodeoxyuridine (BrdU), as a marker of DNA synthesis, was performed in human HeLa, HL60, and in murine Friend leukemia cells (FLC). Field emission in lens scanning electron microscopy analysis of ultrathin cryosections revealed the presence of a regular three-dimensional network of fibers in dispersed chromatin. This spatial architecture was apparently constituted mainly of 10 nm filaments organized in loops of about 80-100 nm. Nodal points and the overlapping of such coils appeared as thicker structures of about 30 nm in diameter. Thin filaments of about 5 nm did not show a regular distribution. This three-dimensional fiber organization seemed quite constant in the dispersed chromatin of all the cell lines analyzed. The DNase treatment of the samples selectively removed the 10 nm class fibers, whereas the BrdU labeling confirmed the presence of newly synthesized DNA organized into chromatin units with a regular arrangement. These data suggest that the 10 nm chromatin fiber likely represents the DNA condensation order at which DNA duplication starts and the main weft of a three dimensional network within the interphase nucleus.

Animals↗
PubMed1999

Cytoreductive surgery in advanced endocrine tumours of the pancreas.

Surgery still plays an important role even in advanced endocrine tumours of the pancreas, owing to their biological behaviour. Sometimes it is possible to attempt a radical approach, but more often only cytoreduction is feasible. In fact, when the malignancy is not completely resectable on account of vessel involvement or extensive liver metastases, surgical reduction of the tumour burden (debulking) can be proposed, aimed at improving the clinical conditions and survival of these patients. Forty-one patients suffering from advanced endocrine tumour of the pancreas were observed from 1985 to 1996. In 13 patients, the disease was locally advanced as far as concerns lymph node metastases and/or vessel involvement, while the other 28 patients presented liver metastases. In the former group, we performed 6 radical resections, in the latter we submitted 2 patients to radical resection and 12 patients to cytoreductive surgery, with complete removal of the pancreatic malignancy. The overall survival of the resected patients was 87% (7/8). Three patients (37.5%) are alive and free of disease, while the other 4 have subsequently developed liver metastases. One patient died with hepatic recurrence. Half the patients (6/12) undergoing cytoreductive surgery are alive, 3 with stable and 3 with progressive disease. The other 6 patients have died due to liver progression of the disease. As data in the literature concerning the role of debulking as regards the survival are conflicting, we have modified our surgical approach in patients with advanced disease. We perform cytoreductive surgery whenever complete removal of the pancreatic tumour is feasible. The rationale of this approach is to leave only a liver with residual disease, with a view to giving targeted adjuvant treatment.

Adolescent↗