Serum selenium concentrations in chronic pancreatitis and controls.

BACKGROUND: In the light of the recent hypothesis that one cause of pancreatic damage may be related to the toxic action of oxygen free radicals [Braganza JM. The pathogenesis of pancreatitis. Manchester: Manchester University Press; 1991; Braganza JM. A framework for the aetiogenesis of chronic pancreatitis. Digestion 1998;59(Suppl. 4):1-12], we were prompted to assess the role of selenium in pancreatic disease. OBJECTIVE: The objective of the study was to establish whether or not there is any correlation between selenium levels and the degree of impairment of exocrine pancreatic function in patients suffering from chronic pancreatitis. PATIENTS: Two groups of subjects were recruited, the first consisting of 38 patients with clinically quiescent chronic pancreatitis of alcoholic origin and the second of 48 control subjects selected from among healthy volunteers attending our Transfusion Centre. METHODS: Body mass index, smoking and drinking habits were evaluated and selenium serum levels were assayed in all subjects. The patients with pancreatic disease were subdivided into three groups on the basis of lipase output assayed with a duodenal probe. RESULTS.: Selenium serum levels in the chronic pancreatitis group as a whole were found to be significantly lower than in the control group, but when they were analysed in the three distinct subgroups, a significant difference was found against control group only in the groups with severe and moderate exocrine pancreatic insufficiency. CONCLUSIONS: The mean serum selenium levels were lower in chronic pancreatitis patients than control.

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.

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.

The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests.

Fecal chymotrypsin (FCT) has been measured by a new photometric method (Monotest Chymotrypsin; Boehringer, Mannheim) in 78 patients: 44 with chronic pancreatitis and 34 not affected by any pancreatic disease. The results were compared with those from other tests of pancreatic secretory (secretin-cerulein test) and digestive [serum and urinary p-aminobenzoic acid (PABA) and pancreolauryl] capacity. When FCT values were severely reduced (below 6.7 U/g), from 90 to 100% of the patients also presented abnormal pancreatic secretory and digestive capacity. On the other hand, 87% of the patients with normal FCT (above 20 U/g) presented normal secretory and digestive capacity. Patients with intermediate FCT values (between 6.7 and 20 U/g) showed normal or abnormal pancreatic secretory and digestive capacity with the same probability. Therefore, FCT, carried out as a first test, seems to identify subjects that need no further pancreatic function tests (normal and severely impaired FCT) and patients who need other more complex functional investigations (intermediate FCT values).

HLA molecule expression on chronic pancreatitis specimens: is there a role for autoimmunity? A preliminary study.

This study was prospectively carried out in order to clarify if an aberrant expression of HLA-DR molecules could take part in the pathogenesis of chronic pancreatitis. Pancreatic specimens from 12 chronic pancreatitis patients and nine controls were examined. Strong HLA-DR expression was observed in 6/12 chronic pancreatitis patients and in 1/9 controls. Moreover, lymphocytic foci with large numbers of activated cells were found only in chronic pancreatitis. The four HLA-DR - patients had a marked increase of fibrous tissue with small portions of acinar tissue, whereas the six patients with strong positivity had the greatest dilatation and hyperplasia of the ducts. These findings are similar to those observed in immune diseases, such as thyroiditis and primary biliary cirrhosis (PBC), and suggest that autoimmune phenomena are involved in chronic pancreatitis.

Effect of alcohol and smoking on pancreatic lithogenesis in the course of chronic pancreatitis.

The aim of the study was to establish whether correlations were discernible between calcification, smoking, and other variables--including alcohol intake--in chronic pancreatitis. A total of 637 patients with chronic pancreatitis diagnosed over the period of 1973-1989 were reviewed. Only patients who had had one or more instrumental tests (ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, plain film of the abdomen) every 3 years were included in the study. Onset of calcification was taken as the end point of the follow-up. No statistically significant correlation was found between alcohol intake and calcification. As regards smoking habits, patients were divided into two groups: nonsmokers and medium-to-heavy smokers (> or = 10 cigarettes/day). Of 637 patients, only 570 fulfilled our criteria. Three hundred seventy-six patients (66%) developed calcifications, whereas 64 (10%) already presented calcifications at the time of diagnosis. Smoking correlated with formation of calcifications (p < 0.004). The mean time to onset of calcification in smokers was 8 years as against 12 years in nonsmokers. The relative risk of calcification in smokers versus nonsmokers was 1.21 (95% confidence limits: 1.10-1.32). By the end of follow-up (17 years), 277 smokers (69%) with chronic pancreatitis had developed calcifications compared with only 93 nonsmokers (55%). The results show that, in this sample of chronic pancreatitis sufferers, smokers present a significantly increased risk of developing calcifications.

Salivary gland involvement in patients with chronic pancreatitis.

The salivary glands are structurally similar to the exocrine pancreas and may be involved in the course of diseases of autoimmune origin (sclerosing cholangitis, ulcerative rectocolitis, primary biliary cirrhosis). For a not-yet-quantified proportion of chronic pancreatitis (CP) cases, a possible autoimmune pathogenesis has been postulated. The aim of the study was to assess the frequency of salivary ductal system abnormalities in patients with CP. Fifty-one patients with CP consecutively admitted to our center were studied (44 men, seven women; mean age, 48.2 +/- 10.8 years). The mean duration of disease was 11.7 years (range, 1-37 years); 44 (86%) of 51 patients had pancreatic calcifications, 25 (49%) of 51 diabetes, 25 (52%) of 48 steatorrhea, and 32 (63%) of 51 underwent pancreatic surgery. As a control group, we studied 10 patients of whom four with liver cirrhosis (three alcoholic and one posthepatitis; three men, one woman; mean age, 57 +/- 12.5 years), and six with temporomandibular pain (five men and one woman; mean age, 42 +/- 10.3 years). The patients were given parotid sialography, the findings being read by two independent observers. In two CP patients, parotid sialography was unsuccessful. Fifteen (31 %) of 49 patients and none of the 10 control patients exhibited abnormalities of the glandular ducts compatible with chronic inflammation of the salivary ducts (p = 0.039). None of the CP patients had salivary intraductal calcifications. Findings of parotid ductal abnormalities are frequent in the course of CP and may indicate a common pathogenetic mechanism, even of an immune type.

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.

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.

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.

Natural history of pancreatitis associated with cystic fibrosis gene mutations.

BACKGROUND: An increased incidence of CFTR mutations has recently been reported in chronic and idiopathic pancreatitis. AIM: The aim of the study was to verify these data and describe the clinical, morphological and histological findings in 99 patients (59 males, 40 females, mean age 40+/-16 years), 45 suffering from idiopathic chronic pancreatitis and 54 from acute recurrent pancreatitis. METHODS: Each subject was screened for the 18 CFTR mutations: DF508, DI507, R1162X, 2183AA>G, 21303K, 3849+10KbC>T, G542X, 1717-1G>A, R553X, Q552X, G85E, 711+5G>A, 3132delTG, 2789+5G>A, W1282X, R117H, R347P, R352Q), which cover 72% of cystic fibrosis chromosomes in the Italian population, plus the 5-thymidine allele in intron 8 of the CFTR gene (IVS85T). RESULTS: Among the 99 patients, we found 14 patients with CFTR mutation (14.1%). Three idiopathic chronic pancreatitis patients had cystic fibrosis (compound mutations in two and a single mutation with a pathological sweat test in one) and 11 (11.1%) presented a single mutation (carriers) (seven idiopathic chronic pancreatitis and four acute recurrent pancreatitis). The incidence of patients with cystic fibrosis was 167.5 times higher than that observed in the general population, whereas the carrier frequency was 4.43 times higher for chronic pancreatitis and 2.11 times for acute recurrent pancreatitis than that observed in 428 unrelated partners of cystic fibrosis patients. The prevalence of IVS8-5T was similar (7.1%) to that of the general population (10%). All idiopathic chronic pancreatitis patients with one or more CFTR gene mutations had a long history of recurrent attacks of pancreatitis. The length of recurrences of pancreatitis before diagnosis of chronic pancreatitis was shorter in chronic pancreatitis patients with one or more CFTR gene mutations than in the other idiopathic chronic pancreatitis patients (7.4+/-5.8 vs. 2.1+/-2 years). In idiopathic chronic pancreatitis patients with one or more CFTR gene mutations, exocrine and endocrine insufficiency (diabetes and steatorrhoea) were rare or delayed events. CONCLUSIONS: The natural history of pancreatitis associated with CFTR gene mutations seems to be characterised by recurrences of pancreatitis which develops into chronic pancreatitis.

Association of keratin 8 gene mutation with chronic pancreatitis.

BACKGROUND: Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue. AIM: To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis. METHODS: Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary. RESULTS: Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, p(c) < 0.003, odds ratio = 21.24, confidence interval = 2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject. CONCLUSION: G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.

High serum levels of secretory immunoglobullin A in chronic pancreatitis.

BACKGROUND AND AIM: Elevated levels of secretory immunoglobulin A have been reported in patients with cholestatic hepatitis. Secretory immunoglobulin A is present in the biliary and pancreatic tract. Chronic pancreatitis is a disease characterized by dilatation of Wirsung's duct. The aim of the study was to evaluate secretory immunoglobulin A levels in patients suffering from chronic pancreatitis. PATIENTS AND METHODS: The study population consisted of 66 consecutive chronic pancreatitis patients (55 male, 11 female; mean age 49.6+/-10 years), 26 patients suffering from acute recurrent pancreatitis (9 males, 17 females; mean age 39.6+/-10.6 years) and 90 healthy controls, pair-matched for sex and age with the chronic pancreatitis patients. Secretory immunoglobulin A was determined by enzyme-linked immunosorbent assay, as were serum alanine transaminase and GGT. RESULTS: Secretory immunoglobulin A levels were significantly higher in chronic pancreatitis patients (35+/-23.7 mg/l) than in those acute recurrent pancreatitis group (16.1+/- 7.9) and in healthy controls (11.8+/-4.9 mg/l) (p<0.0001). Secretory immunoglobulin A was significantly higher in chronic pancreatitis patients with steatorrhoea, diabetes and calcifications and in those undergoing pancreatic surgery. Of 61 chronic pancreatitis patients, 14 (23%) had pathological GGT. When only chronic pancreatitis patients with normal GGT levels were analysed, the differences in secretory immunoglobulin A levels between groups of patients and between chronic pancreatitis subgroups remained statistically significant. CONCLUSIONS: This study demonstrates that secretory immunoglobulin A is elevated in chronic pancreatitis. Its value in the staging of patients needs to be further evaluated.

Effect of graded doses of PGE2 on pancreatic exocrine secretion of bicarbonate, chymotrypsin and cyclic nucleotides during i.v. infusion of secretin in man.

We have previously reported that PGE2 inhibits pancreatic enzyme secretion during Secretin-Caerulein infusion, but differing results have also been reported. In this study 10 tests were performed in 5 healthy volunteers as follows: each subject received secretin (GIH) 2 CU/Kg-h by continuous infusion for 2 hours and, several days later, Secretin at the same dose plus PGE2 (Upjohn) in step-wise doses (0.04-0.08-0.12 gamma/Kg min) increasing every thirty min form 30' to 120' min. Duodenal juice was collected in 10 min samples. The volume of each sample was recorded and bicarbonate, chymotrypsin, cAMP and cGMP contents were determined. Statistical evaluation was performed by Student's "t" test for paired data and the regression test. PGE2 significantly decreased chymotrypsin concentration under Secretin. Both cyclic AMP and GMP Secretin-induced secretions were significantly increased by the highest dose of PGE2. No correlation was found in the behaviour of bicarbonate, chymotrypsin and cyclic nucleotides, but it must be noted that our data concern duodenal contents and not pure pancreatic secretion.

[Medical therapy of chronic idiopathic constipation]. / Terapia medica della stipsi cronica idiopatica.

The medical care of the idiopathic constipation requires the correct patient identification based on precise classification items and on physiopathological considerations. The laxative abuse is often the most difficult problem to be solved and it has to be dealt with the consideration of different clinical aspects (wrong diet, psychological profile, concomitant diseases, drug therapy, etc.). The first step exactly consists in the identification and correction of the wrong convictions, of the behavioural attitudes and of the unbalanced dietary habits. Adding bran is the second widely accepted therapeutic step based on both physiopathological and epidemiological considerations. Even if the mechanism of action is still not completely understood, the fibre addition per se leads to an improvement of the constipation in quite a relevant percentage of patients, although it is often poorly tolerated. Nevertheless there are peculiar conditions not responsive to the bran addition such as the so-called "anismus". For these situations different therapeutic approaches have been proposed with variable results. Among these we can mention the re-educational programmes of the modalities of the defecation using biofeedback techniques. The chronic idiopathic constipation not respondent to the conventional medical therapy appears anyway a problematic and very difficult condition both from the investigational viewpoint and the therapeutic options. Finally it can be stated that the laxatives have a certain role in those clinical conditions most probably leading to the constipation. For each therapeutic drug class it is, of course, of great importance to know its mode of action as well as its adverse event profile.

[Acute adrenal failure due to adrenal hemorrhagic necrosis secondary to heparin-induced thrombocytopenia]. / Insufficienza surrenalica acuta da necrosi emorragica surrenalica secondaria a trombocitopenia indotta da eparina.

The authors describe a clinical case with a peculiar sequence of unhealthy events. An operated by osteotomy woman presented a deep venous thrombosis of lever lower extremity with following pulmonary embolism. The patient was treated with heparin. After 5 days, the patient showed a thrombocytopenia, that was not determined by an immune mechanism. The heparin was stopped and the thrombocythemia returned to normal values. But the patient still presented somnolence, asthenia and hypotension. The tests of adrenocortical function showed below normal values. The abdominal CAT showed haemorrhagic necrosis of the suprarenal glands.

Thrombocytopenic purpura during therapy with simvastatin.

The authors describe a case of very serious thrombocytopenic purpura occurring in a diabetic and hyperlipidemic woman during therapy with simvastatin, an HMG-CoA reductase inhibitor drug. Interruption of the medical treatment produced a prompt reversal of the thrombocytic attack: one year later the patient's platelet count remains within the normal range. The authors have not found other reports in the medical literature of similar serious reactions during therapy with an HMG-CoA reductase inhibiting substance; nevertheless, a causal nexus is hypothesized but not argued in this case, since further studies will be needed before this connection can be established.

Effect of histamine-H2-receptor antagonists on the exocrine pancreatic secretion.

Pancreatic exocrine secretion has been studied in 10 patients with documented duodenal ulcer before and after 4 weeks of cimetidine treatment (1 g/die). This chronic 'short term' cimetidine administration did not result in any substantial modification of exo-pancreatic response stimulated by Secretin and Caerulein. From this point of view the drug could be employed in the treatment of pancreatic insufficiency in order to obtain a better utilization of pancreatic enzyme supplement. It is, however, questionable if such a 'long-term' therapy may be responsible for the appearance or the relapse of a peptic ulcer.