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Biomedical subjects

V Di Francesco

Publications and source records attributed to V Di Francesco.

At least 37 records · Page 2Linked to original sources

Lithostathine messenger RNA expression in different types of chronic pancreatitis.

Lithostathine may play a physiological role in preventing the precipitation of excess calcium in the pancreatic juice. The hypothesis has been advanced that in chronic calcifying pancreatitis the abnormal biosynthesis of lithostathine might be the original defect to which genetic proneness to the disease may be ascribed. The aim of the present work was to study lithostathine messenger RNA expression in the pancreas of patients with different types of pancreatitis. Lithostathine and chymotrypsinogen mRNA were determined in surgical specimens obtained from the pancreases of the following subjects: (a) 13 patients with chronic alcoholic pancreatitis (84.6% calcified); (b) 4 patients with chronic hereditary pancreatitis (all calcified); (c) 6 patients with chronic obstructive pancreatitis (4 calcified); and (d) 27 subjects suffering from pancreatic cancer. Significantly lower concentrations of both mRNAs were found in the pancreases of chronic pancreatitis patients than in non-cancerous tissue from pancreatic cancer subjects. However, about 70% of the pancreatic cancer subjects showed lithostathine and chymotrypsinogen mRNA levels comparable to those of chronic pancreatitis patients. These results indicate that the decrease in the level of mRNA is not specific to lithostathine and it is unrelated to the presence of pancreatic stones.

Adult↗

Long-term follow-up of patients with chronic pancreatitis in Italy.

BACKGROUND: We investigated the epidemiologic, clinical, and radiologic aspects of a mixed medicosurgical series of chronic pancreatitis patients observed at the University of Verona Centre for the Study of Pancreatic Diseases over the period 1971-1995. METHODS: Even though the pathogenesis of chronic pancreatitis has yet to be clarified and the classification is still debatable, the patients were subdivided in accordance with the Marseilles-Rome classification into those with alcoholic, obstructive, familial, and idiopathic forms of the disease. A total of 715 patients were analysed with a median follow-up period of 10 years (range, 1-25 years). RESULTS AND CONCLUSIONS: At the end of follow-up the dropout rate amounted to 7.1% (51 patients), and 176 patients (24.6%) had died. Data are reported about the type of chronic pancreatitis, sex, and age distribution at the onset of the disease, drinking and smoking habits before onset and during follow-up, and incidence of calcifications, pain, diabetes, steatorrhoea, and pseudocysts. Surgical aspects, survival curves, and causes of death are also analysed, and the most frequent concomitant diseases in chronic pancreatitis sufferers are discussed.

Adolescent↗

Protein topology recognition from secondary structure sequences: application of the hidden Markov models to the alpha class proteins.

The three-dimensional fold of a protein is described by the organization of its secondary structure elements in 3D space, i.e. its "topology". We find that the protein topology can be recognized from the ID sequence of secondary structure states of the residues alone. Automated recognition is facilitated by use of hidden Markov models (HMMs) to represent topology families of proteins. Such models can be trained on the experimentally observed secondary structure sequences of family members using well established algorithms. Here, we model various topology groups in the alpha class of proteins and identify, from a large database, those proteins having the topology described by each model. The correct topology family for protein secondary structure sequences could be recognized 12 out of 14 times. When the observed secondary structure sequences are replaced with predicted sequences recognition is still achievable 8 out of 14 times. The success rate for observed sequences indicates that our approach will become increasingly useful as the accuracy of secondary prediction algorithms is improved. Our study indicates that the HMMs are useful for protein topology recognition even when no detectable primary amino acid sequence similarity is present. To illustrate the potential utility of our method, protein topology recognition is attempted on leptin, the obese gene product, and the human interleukin-6 sequence, for which fold predictions have been previously published.

Algorithms↗

Fold recognition using predicted secondary structure sequences and hidden Markov models of protein folds.

We present an analysis of the blind predictions submitted to the fold recognition category for the second meeting on the Critical Assessment of techniques for protein Structure Prediction. Our method achieves fold recognition from predicted secondary structure sequences using hidden Markov models (HMMs) of protein folds. HMMs are trained only with experimentally derived secondary structure sequences of proteins having similar fold, therefore protein structures are described by the models at a remarkably simplified level. We submitted predictions for five target sequences, of which four were later found to be suitable for threading. Our approach correctly predicted the fold for three of them. For a fourth sequence the fold could have been correctly predicted if a better model for its structure was available. We conclude that we have additional evidence that secondary structure information represents an important factor for achieving fold recognition.

Algal Proteins↗

Food intake of patients with chronic pancreatitis after onset of the disease.

The food intake of 40 male patients with chronic pancreatitis followed up at our center for > or = 10 y were compared with that of 75 healthy control subjects. Patients had significantly lower anthropometric values and serum triacylglycerol and cholesterol concentrations than control subjects (P < 0.001). Subjects with pancreatitis had higher carbohydrate and energy intakes than control subjects but no significant differences were observed in protein, fat, fiber, or cholesterol intakes. The results show that although those with chronic pancreatitis consumed carbohydrates with a more balanced variety of nutrients, they were thinner and had lower serum lipid concentrations, which suggests that they had latent digestion disorders or malabsorption.

Adult↗

Ultrasonography-secretin test pattern after acute administration of octreotide in healthy persons and in patients with recurrent acute pancreatitis.

The intravenous administration of octreotide stimulates sphincter of Oddi activity and impairs pancreatic flow into the duodenum. Postsecretin ultrasonography (US-S test) has revealed an increase in the caliber of the main pancreatic duct, which disappears in healthy persons approximately 10 minutes later as a result of the opening of the sphincter of Oddi and passage of stimulated fluids into the duodenum. We have assessed US-S test patterns after octreotide in healthy persons and in patients with recurrent acute pancreatitis. The study sample consisted of 16 participants: alcohol-abstinent, nonsmoking, healthy volunteers (four men, three women; mean age: 28 +/- 2.5 years) and nine patients with recurrent acute pancreatitis (six men, three women; mean age: 32.1 +/- 7.1 years). All participants underwent measurement of the main pancreatic duct at 1-min intervals for 60 min after secretin stimulation (1 IU/kg intravenous bolus). On a different day the same persons had repeated US-S tests 1 hour after administration of 0.1 mg octreotide intramuscularly. In both controls and patients with recurrent acute pancreatitis, octreotide administration induced an appreciable dilatation of the main pancreatic duct before secretin stimulation, and the caliber remained significantly increased throughout the duration of the test. These results suggest that a single administration of octreotide at the dose used (a) does not inhibit pancreatic secretion of basal and secretin-stimulated fluid within the first 60 min and (b) probably exerts an inhibitory effect on sphincter of Oddi relaxation. These findings warrant more intensive study given their therapeutic implications for acute pancreatic disease.

Acute Disease↗

Incorporating global information into secondary structure prediction with hidden Markov models of protein folds.

Here we propose an approach to include global structural information in the secondary structure prediction procedure based on hidden Markov models (HMMs) of protein folds. We first identify the correct fold or 'topology' of a protein by means of the HMMs of topology families of proteins. Then the most likely structural model for that protein is used to modify the sequence of secondary structure states previously obtained with a prediction algorithm. Our goal is to investigate the effect on the prediction accuracy of including global structural information in the secondary structure prediction scheme, by means of the HMMs. We find that when the HMM of the predicted topology of a protein is used to adjust the secondary structure sequence predicted originally with the Quadratic-Logistic method, the cross-validated prediction accuracy (Q3) improves by 3%. The topology is correctly predicted in 68% of the cases. We conclude that this HMM based approach is a promising tool for effectively incorporating global structural information in the secondary structure prediction scheme.

Algorithms↗

Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy--Italian Group.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP. METHODS: We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years)--208 in the gabexate group and 210 in the placebo group--were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain. RESULTS: After the procedures, 276 patients (66 percent) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups. Mean serum amylase values were higher in the placebo group than in the gabexate group through 24 hours of observation (P=0.03). Twelve patients in the gabexate group and 29 in the placebo group had abdominal pain (6 percent vs. 14 percent, P=0.009). Sixteen patients in the placebo group and five in the gabexate group had acute pancreatitis (8 percent vs. 2 percent, P=0.03). Two patients treated with gabexate and six given placebo had adverse events, all of which resolved. Two patients given placebo died of acute pancreatitis; one was excluded from the evaluation because pancreatitis was present before endoscopy. One patient in the gabexate group died, from a myocardial infarction. CONCLUSION: Prophylactic treatment with gabexate reduced pancreatic damage related to ERCP, as reflected by reductions in the extent but not the frequency of elevated enzyme levels and in the frequency of pancreatic pain and acute pancreatitis.

Acute Disease↗

Improving protein secondary structure prediction with aligned homologous sequences.

Most recent protein secondary structure prediction methods use sequence alignments to improve the prediction quality. We investigate the relationship between the location of secondary structural elements, gaps, and variable residue positions in multiple sequence alignments. We further investigate how these relationships compare with those found in structurally aligned protein families. We show how such associations may be used to improve the quality of prediction of the secondary structure elements, using the Quadratic-Logistic method with profiles. Furthermore, we analyze the extent to which the number of homologous sequences influences the quality of prediction. The analysis of variable residue positions shows that surprisingly, helical regions exhibit greater variability than do coil regions, which are generally thought to be the most common secondary structure elements in loops. However, the correlation between variability and the presence of helices does not significantly improve prediction quality. Gaps are a distinct signal for coil regions. Increasing the coil propensity for those residues occurring in gap regions enhances the overall prediction quality. Prediction accuracy increases initially with the number of homologues, but changes negligibly as the number of homologues exceeds about 14. The alignment quality affects the prediction more than other factors, hence a careful selection and alignment of even a small number of homologues can lead to significant improvements in prediction accuracy.

Amino Acid Sequence↗

Effect of octreotide on sphincter of Oddi motility in patients with acute recurrent pancreatitis: a manometric study.

Sphincter of Oddi dysfunction has been reported as a cause of acute idiopathic recurrent pancreatitis (IRP). Octreotide, a long-acting somatostatin analogue, is an antisecretory drug used in the treatment and prevention of acute pancreatitis. Its action on sphincter of Oddi motility is controversial and no data are available for IRP patients. The aim of this study was to assess sphincter of Oddi motor response to acute administration of octreotide in patients with past attacks of acute pancreatitis without identification of any evident aetiological factor. Six patients (four male, two female; mean age +/-SD, 38.8+/-9 years) suffering from acute pancreatitis for at least 3 months before the examination were submitted to sphincter of Oddi manometry. After a basal recording lasting at least 2 min, octreotide, 0.05 mg i.v., was administered and the recording repeated. Intraduodenal pressure was taken as the zero reference and the basal sphincter of Oddi pressure and amplitude and frequency of phasic contractions were calculated before and after octreotide administration. No significant pre- vs post-octreotide differences were observed in basal pressure (41.9+/-24 vs 47.5+/-33 mm Hg, respectively) or in amplitude of phasic contractions (164.6+/-33 vs 170.8+/-18 mm Hg). With a latency of about 1 min, octreotide administration caused a high-frequency phasic activity in all cases (mean frequency, 5.5+/-2.2 contractions/min before and 9.8+/-2 after octreotide; P < 0.04). After the procedure acute pancreatitis (prolonged abdominal pain and serum amylase levels more than three-fold the normal values) developed in five patients. In conclusion, our data suggest that acute administration of octreotide may induce tachyoddia and thus a rise in sphincter of Oddi pressure, with possible impairment of biliary-pancreatic outflow.

Acute Disease↗

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↗

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↗

Division of the sphincter of Oddi for treatment of dysfunction associated with recurrent pancreatitis.

Increasing evidence suggests that motility disorders of the sphincter of Oddi may lead to episodes of recurrent pancreatitis in a small proportion of patients with the diagnosis of idiopathic recurrent pancreatitis. Over 10 years, 35 patients have been identified and treated for this condition. The aim of the study was to assess symptomatic outcome in these patients. Following the exclusion of common causes of pancreatitis the patients underwent sphincter of Oddi manometry. Patients with manometric abnormalities and three with normal manometric findings underwent treatment. Twenty-six patients with persistent symptoms underwent total division of the sphincter via open sphincteroplasty and septectomy. Patients were followed up according to symptoms and classed as having a cure, mild symptoms or no change. At a median follow-up of 24 (range 9-105) months, 15 of the 26 patients were cured, eight had only mild symptoms and three remained unchanged. In the majority of patients with a good clinical outcome, manometry had demonstrated sphincter of Oddi stenosis. Total division of the sphincter of Oddi is associated with good symptomatic outcome in patients with recurrent episodes of pancreatitis and documented sphincter of Oddi stenosis.

Adult↗

Chronic obstructive pancreatitis in humans is a lithiasic disease.

In humans chronic obstructive pancreatitis (COP) is thought to be a disease devoid of ductal stones. The aim of this study was to verify the presence and frequency of calcifications in patients with COP and compare them with those found in patients with chronic calcifying/calcific pancreatitis (CCP). We conducted a retrospective ERCP investigation in 115 patients with documented chronic pancreatitis. Only 75 could be safely classified as COP or CCP. Fifty-three patients (M:F ratio, 5.6:1; mean age, 36.1 +/- 12.2 years) had CCP, 46 of whom (86.8%) with calcifications. Twenty-two patients (M:F ratio, 3.4:1; mean age, 45.3 +/- 16.2 years; p < 0.05 vs. CCP) presented COP at endoscopic retrograde cholangiopancreatography, 8 (36.4%) with ductal calcifications (p < 0.0001 vs. CCP). COP was secondary to acute pancreatitis in nine cases, to odditis in 11 cases, and to malignant tumor and hypertrophy of Oddi's sphincter, respectively, in the other two cases. The two patient groups showed no significant differences in drinking and smoking habits, number of painful relapses, disease duration, and incidence of diabetes, gallstones, and need for surgery. In conclusion, formation of ductal stones is by no means rare in COP and should be classified as a form of lithiasic pancreatitis. Early restoration of pancreatic outflow by removing the obstruction, or by shunt-type operations and abstinence from drinking and smoking, should resolve this type of disease.

Adult↗