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Biomedical subjects

M Falconi

Publications and source records attributed to M Falconi.

180 records · Page 10Linked to original sources

Correlative high-resolution morphologic analysis of the three-dimensional organization of human chromosomes.

A correlative morphologic analysis was carried out on isolated metaphase chromosomes by means of field emission in-lens scanning electron microscopy (FEISEM) and atomic force microscopy (AFM). Whereas FEISEM provides ultra-high resolution power and allows the surface analysis of biological structures free of any conductive coating, the AFM allows imaging of biological specimens in ambient as well as in physiologic conditions. The analysis of the same samples was made possible by the use of electrical conductive and light transparent ITO glass as specimen holder. Further preparation of the specimen specific for the instrumentation was not required. Both techniques show a high correlation of the respective morphologic information, improving their reciprocal biological significance. In particular, the biological coat represents a barrier for surface morphologic analysis of chromosome spreads and it is sensitive to protease treatment. The chemical removal of this layer permits high-resolution imaging of the chromatid fibers but at the same time alters the chromosomal dimension after rehydration. The high-resolution level, necessary to obtain a precise physical mapping of the genome that the new instruments such as FEISEM and AFM could offer, requires homogeneously cleaned samples with a high grade of reproducibility. A correlative microscopical approach that utilizes completely different physical probes provides complementary useful information for the understanding of the biological, chemical, and physical characteristics of the samples and can be applied to optimize the chromosome preparations for further improvement of the knowledge about spatial genome organization.

Chromosomes, Human↗

Pancreatic abscess and other pus-harboring collections related to pancreatitis: a review of 108 cases.

This is a report on 108 cases collected from 1970 to 1987, in the same department, of surgically-detected pancreatic abscesses or pus-harboring collections. The purulent areas were either of a spreading pattern or represented a clearly localized mass. To the spreading pattern belong 47 cases of necrotizing pancreatitis, without discontinuity in the clinical course from the early toxic to the late septic phase, 4 cases of acute pancreatitis, initially in remission and later complicated by septic collections, and 4 cases which developed after an acute attack of chronic pancreatitis. The abscess pattern was made up of 19 each of pseudocysts and predisposing pancreatitis, 10 cases of chronic pancreatitis, and only 5 necrotizing "nonstop" pancreatitis. The surgical treatment in all cases consisted of multiple drainages and postoperative irrigation. We exclude 3 cases of associated open packing. The etiological, clinical, and biochemical features of each group of patients are reported and discussed. Computed tomography availability seems to be the most important improvement reported as regards diagnosis and surgical tactics. The overall mortality rate was 15.7% with a significant difference between the 2 patterns (23.6% for the spreading pattern versus 7.5% for the abscess pattern). On the basis of this experience, it is possible to establish a relationship between the gross appearance of the collection and the underlying pancreatic disease with differences in terms of prognosis, morbidity, and mortality. Finally, a simple nomenclature can be chosen which is capable of distinguishing between the diverse pancreatic purulent collections. While the presence of pus may characterize the course of severe acute pancreatitis in many cases, the low incidence of "true" pancreatic abscess is emphasized.

Abscess↗

Antibacterial and mezlocillin-enhancing activity of pure human pancreatic fluid.

The majority of deaths in severe pancreatitis are the result of superinfection of necrotic tissue. The pathogen most commonly responsible for such infections is Escherichia coli. Antibiotic prophylaxis would appear a logical precaution. The antibacterial drugs of choice should possess two basic characteristics: they must be active against the flora responsible for the infections and must be capable of penetrating into the pancreas at adequate minimum inhibitory concentrations (MICs). Mezlocillin--which is active against E. coli--has been shown to possess the latter requisite, but achieving therapeutic concentrations requires administration at high doses. In the present study, pure human pancreatic fluid showed properties similar to those observed in the dog against E. coli (bacterial colony growth 100 times lower than in a control culture) and produced a 75% reduction in mezlocillin MICs against this organism. These enhancing characteristics might make the commonly used doses sufficient for prophylactic purposes.

Colony Count, Microbial↗

Ultrasonography of the pancreas. 7. Intraoperative imaging.

The usefulness of intraoperative ultrasonography (IOUS) has been documented in the Literature since the Eighties and, although its main applications are in hepatobiliary and pancreatic surgery, it has been used also in neurosurgery, cardiovascular and endocrine surgery. The continuous technical developments have led to an increase in the diagnostic accuracy of IOUS from the Eighties to now. The use of IOUS has increased in time together with the technical innovations until, mainly in the midnineties, its value was recognized by many surgeons. This results have been obtained with scanners that allow to depict fine anatomical details and detect small lesions in real time with extremely high spatial resolution. IOUS is able to shows fine details, such as primary or secondary lesions not detectable with other preoperative imaging modalities or tumor extension and its relationship with vessels. Assessment of resectability by IOUS may determine important changes in therapeutic planning. The role of IOUS, however, has recently been down-sized, especially in those centers where preoperative imaging is advanced. This article will review the clinical role of pancreatic IOUS in the different pancreatic pathologies.

Humans↗

Early detection of pancreatic cancer following the diagnosis of chronic pancreatitis.

AIM: To assess whether patients with misdiagnoses of chronic pancreatitis (CP), followed at an early stage by a diagnosis of pancreatic cancer (PCr), present different epidemiological characteristics from patients suffering either from CP alone or from CP with late degeneration to PCr. METHODS: We arbitrarily subdivided our patient series into three groups: (1) 12 CP who developed PCr within 4 years after onset of symptoms; (2) 12 CP developing PCr after the 4th year, and (3) 701 CP with no subsequent development of PCr. The variables studied were age, sex, drinking and smoking habits, tumor localization, and presence of intraductal calcifications and diabetes mellitus at the time of diagnosis of CP. RESULTS: There were no significant differences between CP and 'late' PCr in any of the study variables considered. As compared with the CP group, the 'early' PCr cases were older (58.7 vs. 40.7 years; p < 0.0001), with a lower proportion of males (58 vs. 88%; p < 0.01), smaller proportions of both smokers (42 vs. 88%; p < 0.0001) and subjects drinking more than 40 g of alcohol/day (42 vs. 86%; p < 0. 0001), and a greater incidence of non-insulin-dependent diabetics at the time of diagnosis of CP (25 vs. 3.7%; p < 0.012). As compared with the 'late' PCr group, the malignancies in the 'early' PCr cases were more often located in the head of the pancreas (100 vs. 50%; p < 0.01). Multivariate logistic regression analysis selected age over 50 (odds ratio OR 13.5, 95% confidence interval CI 2.79-65.5; p < 0. 001), smoking habits (OR 0.14, 95% CI 0.04-0.49; p < 0.002), and non-insulin-dependent diabetes (OR 5.91, 95% CI 1.20-29.1; p < 0. 028) as variables identifying subjects with 'early' PCr. CONCLUSIONS: A high suspicion of a pancreatic tumor is necessary when CP is diagnosed in a patient with atypical epidemiological characteristics for this condition, possibly female, aged over 50, who is not a smoker or drinker, and suffers from non-insulin-dependent diabetes.

Adult↗

Nuclear phospholipase C: a novel aspect of phosphoinositide signalling.

The role of polyphosphoinositides in cellular signalling is well known and recently it has also been shown that the nucleus is a site for both synthesis and hydrolysis of the phosphorylated forms of phosphatidylinositol. It has been demonstrated that phospholipase C specific for inositol lipids (PLC) is one of the main steps of the inositol lipid cycle. The PLC beta family, and especially type beta 1, has given rise to considerable interest since, due to their common COOH-terminus they show nuclear localisation in addition to that at the plasma membrane. It is well established that an autonomous intranuclear inositide cycle exists, and that this cycle is endowed with conventional lipid kinases, phosphatases and PLCs. Among this latter the beta 1 type undergoes stimulation or inhibition under different stimuli and this implicates the beta 1 isoform as a key enzyme for mitogen-activated cell growth as well as for differentiation. Indeed, both the overexpression and the down-regulation of PLC beta 1, by means of antisense mRNA, have demonstrated that PLC plays a role in the nuclear compartment.

Animals↗

[Quality of life assessment in pancreatic carcinoma: results of an European multicentric study].

Quality of life (Qol) assessment is a mandatory endpoint of cancer clinical trials. Little research has been conducted on pancreatic cancer (Pc) and no disease specific Qol questionnaire exists. We report on the development of the European Organization for Research and Treatment of Cancer (EORTC) Pc Qol module to supplement the core cancer module (QLQ-C30). Literature research and qualitative interviews with 6 specialists and 34 patients in the UK were followed by construction of a questionnaire, a peer review by international specialists and EORTC. Administration of the QLQ-C 30, a provisional Pc module and a qualitative debriefing interview was performed on 78 patients in 8 countries stratified into groups by disease stage and treatment intention. Pretesting identified that 23/26 questions had an adequate internal reliability (Cronbach's alpha > 0.7) and construct validity (Pearson's r 0.4-0.6). The median time of completion was 12 mins. Qualitative analysis indicates that the module is easy to complete and cross culturally applicable. The EORTC QLO-PAN 26 includes 26 items covering symptoms, body image, sexuality and the emotional and social consequences of Pc. It is intended for use in patients undergoing clinical trials for pancreatic cancer including surgery, chemotherapy and radiotherapy and will allow the detection of small but clinically meaningful differences in clinical trials for Pc.

Adult↗

Resection in chronic pancreatitis: anastomosis with the jejunum or with the stomach?

Even in centers where the first choice in the surgical treatment of chronic pancreatitis is a derivative procedure some selected patients require resection. The most popular solution of gastrointestinal reconstruction still seems to be pancreaticojejunostomy but, the review of the reported experiences, suggests a general trend towards anastomosis with the stomach as a recent policy. A reliable comparison between pancreaticogastrostomy and pancreaticojejunostomy is difficult because the reported series are seldom related to chronic pancreatitis patients only, but are reporting mixed date concerning mainly periampullary cancer. Moreover with only one exception no prospective randomised clinical trails are available; unfortunately the positive trend in favour of pancreaticogastrostomy reported in uncontrolled studies is not confirmed in the randomized setting. Also the comparison between the experiences achieved by the present authors working in centers with different approach to the pancreatic anastomosis does not show statistical significant difference for both morbidity and mortality. In conclusion nowadays the best confidence and experience with any of the two methods represents the basis of choice.

Anastomosis, Surgical↗

[Clinical evolution of chronic pancreatitis and quality of life].

Nowadays the availability of reliable, efficacious methods of assessing the outcome of chronic pancreatitis is mandatory, especially in view of the several new procedures developed to relieve the symptoms of the disease. Together with the traditional evaluation of postoperative morbidity and mortality and the assessment of exo/endocrine function in patient follow-up, we currently consider the patient's perception of his or her health status as a priority. This information is obtained by administering quality of life questionnaires along with reliable physical and psychometric evaluation.

Abdominal Pain↗

[Does locoregional chemotherapy improve survival in patients with non-resectable pancreatic carcinoma? Results of an open controlled study].

About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.

Adult↗

[Gabexate mesilate vs gabexate mesilate combined with octreotide in the prevention of postoperative complications of pancreatic surgery: preliminary results].

To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.

Adolescent↗

[Intermediate resection and distal pancreatectomy for benign neoplasms of the pancreas: comparison of postoperative complications and costs].

The middle pancreatic resection for benign pathology of the pancreas has been proposed as an advantageous alternative to the distal pancreatectomy, even though the risk of complications is greater. The purpose of the present study is to compare the cost and intra and perioperative impact for the 2 procedures. All patients with benign neoplasia of the body and tail of the pancreas operated on from 1990-1999 were selected from our computer archives, 21 patients underwent an intermediate resection and 64 a distal pancreatectomy. Operative time, units transfused, perioperative complications, post-operative stay and cost were compared. Statistical analysis revealed that the 2 operations are not significantly different in the intra-operative period. Comparing serious complications, the percentage of pancreatic fistulas (33% vs. 11%; P < 0.03) and average hospital stay (21.2 +/- 11.7 days vs. 15.5 +/- 7.1 days; p = 0.009) are greater for the middle than distal resection, respectively. In cases with post-operative complications the hospital stay is even more significant (middle 31.8 +/- 10.3 days vs. 19.1 +/- 7.6 days; p = 0.0002). The economic margin of residual costs, calculated by using the difference of DRG (no 192) and average post-operative costs, is similar for the 2 procedures in cases with normal post-operative courses, (intermediate Euro 2890.02; distal Euro 3181.9), while in cases with complications (DRG no 191), the difference increases (intermediate Euro 8670.11; distal Euro 12788.94). The middle pancreatic resection in respect to the distal pancreatectomy presents a greater technical difficulty when you take into account the longer post-operative course, the increased difficulty in treating complications and the increased costs.

Adolescent↗

Cystic tumours of the pancreas: a review.

The detection of a cystic tumour of the pancreas is a challenge which puts not only the surgeon's knowledge and expertise to the test, but also those of the team of radiologists and pathologists with whom he works. The diagnosis of a suspected pancreatic cystic tumour is morphological and is based on modern imaging techniques and, in the case of intraductal papillary mucinous tumours, on endoscopic findings. In the search for the correct preoperative diagnosis, however, it is of fundamental importance to bear in mind the limitations of the various instrumental investigations, and particularly those of fine-needle aspiration cytology. In this light the main morphological and clinicopathological features of serous cystadenomas, mucinous adenomas and adenocarcinomas, intraductal papillary mucinous tumours and papillary cystic and solid tumours are analysed as well as the surgical indications. In fact only the surgeon, on the basis of his knowledge of the patient's medical history and symptoms, will be in a position to determine to which nosological "cystic" entity the morphological findings described belong. A deeper knowledge of the natural history of each of these cystic tumours will help the surgeon formulate the most appropriate treatment indication. Providing the patient's condition fulfills the necessary operability criteria, resection will be mandatory whenever there exists a doubt that the tumour may be malignant or whenever its natural history suggests a malignant potential.

Cysts↗

Gemcitabine and continuous infusion of 5-fluorouracil in locally advanced and metastatic pancreatic cancer: a phase I-II study.

BACKGROUND: Gemcitabine has been recently recognized as standard treatment in advanced pancreatic cancer. To potentiate its single-agent activity we conducted a phase I-II study with the primary objective of establishing the maximum tolererated dose (MTD) of gemcitabine and continuous infusion 5-FU in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Fifteen patients received a fired dose of 5-FU 200 mg/mq protracted infusion for six months. Gemcitabine was administered weekly for three out of four weeks for six cycles at escalating doses of 800 mg/mq to 1100 mg/mq. RESULTS: MTD was established at 1000 mg/mq of gem citabine. Of the 11 evaluable patients, 7 patients had stable disease, 1 had partial response and 3 had progressive disease. Of the 14 patients evaluable at follow-up, median time to progression was 5 months. Median survival was 10 months. CONCLUSION: This study confirms the good tolerability of the combination, of gemcitabine with 5-FU.

Adenocarcinoma↗

Necrosectomy by lavage in the surgical treatment of severe necrotizing pancreatitis. Results in 263 patients.

A conservative surgical technique for treatment of necrotizing pancreatitis is described. Standardized since 1976, the technique is based on washout mechanical necrosectomy accomplished by lavages via intraoperatively placed wide-bore drainage tubes. The overall mortality rate from necrotizing pancreatitis was thereby reduced from 61% (with resective technique) to 18%, and in 106 cases observed from the onset of the disease the mortality fell to only 6.6%. The series included also patients with fulminant acute pancreatitis and multiorgan failure.

Acute Disease↗

Acute nonlymphocytic leukemia in the elderly: results of a retrospective study.

Seventy-four patients over 60 years of age with new cases of ANLL diagnosed between January, 1980 and December, 1986 were retrospectively evaluated. Twenty-nine (median age 63, range 60-70) received aggressive induction polychemotherapy: 15 achieved CR (52%), 10 were resistant (34.5%) and 4 died during induction (13.5%). Overall median survival was 6 1/2 months, median CR duration and median survival of responders were 9 and 13 months, respectively. Eight patients (median age 70.4, range 64-74) received low doses of Ara-C: 2 achieved CR, 5 were resistant and 1 died during induction, with an overall median survival of 6 1/2 months; 37 patients (median age 72, range 60-86) received only supportive care and cytostatic therapy for disease control with Hydroxyurea and 6-Mercaptopurine if WBC greater than 20 x 10(9)/l: overall median survival was 6 months and 2 patients are still alive after 18 and 26 months. Aggressive chemotherapy seems to be the treatment of choice in patients less than or equal to 70 years, while for those over 70 current supportive care may offer good survival and a good quality of life.

Aged↗

Gabexate mesilate in the treatment of acute pancreatitis.

Despite controversial experimental and clinical findings, the use of Aprotinin (A) in the treatment of acute pancreatitis (AP) is still widespread in our country. Compared to A, Gabexate Mesilate (FOY) should have the following advantages: lack of antigenicity, low molecular weight with better cellular penetrance, wide inhibitory spectrum (against phospholipase A2 too) and good tolerability. In order to verify the efficacy of FOY versus, we decided to carry out a prospective multicenter (34 centers) randomized double blind trial in moderate-severe AP with FOY 3g/day versus A 1,500,000 U.I.K./day infused for 7 days with central venous line. Based on standard clinical, biochemical and radiological data, 199 patients suffering from AP were enrolled to the study from January 1989 to December 1990. The main admission criteria were: onset of the disease from no more than 72 hours, at least 2 Ranson positive criteria and C.T. evidence of acute pancreatic damage. Seventeen no protocol patients were excluded. The Etiology in the 182 analyzed patients (106 male, 76 female; mean age 57.6 years, range 21-91) were: biliary 102 (56%), alcohol 47 (25.8%), post-operative 13 (7.1%), unknown causes 13 (7.1%) and others 7 (3.8%). Median Ranson's Score was 3. CT examination showed 66 AP with edema, while 116 cases (63.7%) were recognized as severe forms with pancreatic necrotic involvement of 30% of the gland in 71 (61.2%), 50% in 31 (26.7%), and more than 50% in 14 (12.1%). Out of 182 patients, 91 were treated with A and 91 with FOY. The two groups were comparable regarding the main prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗