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Background & Aims: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients., Methods: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy., Results: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively)., Conclusions: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Background: We report the use of a thorough intraoperative sentinel lymph node (SLN) biopsy screening procedure for patients with small N0 breast tumors., Methods: Sixty-eight consecutive female patients with monofocal stage I or "small" stage II (ie, 2.1-3.0 cm) N0 tumors received intraoperative SLN screening according to a procedure on the basis of comprehensive histologic analysis and cytokeratin immunohistochemical determination (CkID) of adjacent frozen sections of the SLN taken at 50-microm cutting levels., Results: The maximum duration of intraoperative analysis including CkID was 40 minutes. Positive SLN were found in 15/68 (22%) patients (always in a single node); they included 5 instances of micrometastasis and 3 of carcinomatous lymphangitis. In the 14 patients who underwent axillary lymph node dissection, no further metastasis was found at histologic analysis or CkID. SLN positivity correlated with histologic type (P=.044), intratumoral or peritumoral vascular invasion (P<.001) and Mib1 score (P=.042)., Conclusions: It is possible for an experienced team to perform intraoperative SLN screening for T1 or small T2 N0 breast tumors with frozen sections taken at 50-microm cutting levels. This procedure facilitates identification of micrometastasis, as well as of carcinomatous lymphangitis to help understand the biologic implications of these small lesions in the long term. SLN positivity appears to correlate with histologic type, intratumoral/peritumoral vascular invasion and Mib1 score.

Background: In mild head injury, predictors to select patients for computed tomography (CT) and/or to plan proper management are needed. The strength of evidence of published recommendations is insufficient for current use. We assessed the diagnostic accuracy and the clinical validity of the proposal of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies on mild head injury from an emergency department perspective., Methods: In a three year period, 5578 adolescent and adult subjects were prospectively recruited and managed according to the proposed protocol. Outcome measures were: (a) any post-traumatic lesion; (b) need for neurosurgical intervention; (c) unfavourable outcome (death, permanent vegetative state or severe disability) after six months. The predictive value of a model based on five variables (Glasgow coma score, clinical findings, risk factors, neurological deficits, and skull fracture) was tested by logistic regression analysis., Findings: At first CT evaluation 327 patients (5.9%) had intracranial post-traumatic lesions. In 16 cases (0.3%) previously undiagnosed lesions were detected after re-evaluation within seven days. Neurosurgical intervention was needed in 71 patients (1.3%) and an unfavourable outcome occurred in 39 cases (0.7%). The area under the ROC curve of the variables in predicting post-traumatic lesions was 0.906 (0.009) (sensitivity 70.0%, specificity 94.1% at best cut off), neurosurgical intervention was 0.926 (0.016) (sensitivity 81.7%, specificity 94.1%), and unfavourable outcome was 0.953 (0.014) (sensitivity 88.1%, specificity 95.1%)., Interpretation: The variables prove highly accurate in the prediction of clinically meaningful outcomes, when applied to a consecutive set of patients with mild head injury in the clinical setting of a 1st level emergency department.

Background: Hyperandrogenism, hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome (PCOS), contributing in different ways to the clinical expression of the syndrome. Weight loss is beneficial, but the additional administration of insulin-lowering drugs, such as metformin, and antiandrogens may produce further benefits, due to their different spectrum of action. The effects of long-term metformin and flutamide, an antiandrogen drug, added alone or in combination with a low-calorie diet, on body weight and fat distribution, androgens, metabolic parameters and clinical status in obese women with PCOS were investigated., Methods: Forty obese women with PCOS were enrolled in the study. After a 1-month diet, according to single-blind design, the patients were allocated to treatment with placebo, metformin (850 mg/orally, twice daily), flutamide (250 mg/orally, twice daily) or metformin (850 mg/orally, twice daily) + flutamide (250 mg/orally, twice daily) for the following 6 months, while continuing hypocaloric dieting. At baseline and at the end of the study, sex hormone, SHBG, lipid, insulin and insulin sensitivity determinations were evaluated. At the same time, clinical parameters such as anthropometry, total (TAT), visceral (VAT) and subcutaneous (SAT) adipose tissue, hirsutism and menses were also measured., Results: We found that, in obese PCOS women, following a hypocaloric diet the addition of metformin, flutamide or the combined metformin + flutamide treatment had some specific additional favourable effects with respect to the low-calorie diet alone. In particular, flutamide treatment seemed to add a significant effect in decreasing visceral fat, androstenedione, DHEA-S, total and low density lipoprotein (LDL) cholesterol and in improving hirsutism. Conversely, metformin had significant benefits on the menstrual status. The two drugs showed an additive effect in reducing testosterone concentrations and a synergistic effect in increasing high density lipoprotein (HDL) cholesterol and SHBG levels. Improvement of insulin sensitivity and hyperinsulinaemia appeared to depend on hypocaloric diet, without any further significant effect of the pharmacological treatments, either alone or in combination., Conclusions: We conclude that, in obese PCOS women, following a hypocaloric diet the addition of metformin, flutamide or the combined metformin + flutamide treatment appears to have a more favourable outcome on body fat distribution, androgens, lipids, hirsutism and menses. However, our data emphasize the dominant role of hypocaloric dieting in improving insulin resistance and hyperinsulinaemia. Therefore, this study provides a rationale for specifically targeting different therapeutical options for PCOS according to the required outcomes.

In this study we evaluated whether testosterone undecanoate (TU), alone or combined with low dose cyproterone acetate (CPA), can maintain spermatogenic suppression induced by higher doses of CPA plus TU. Twenty-four men received for 12 wk 20 mg/d CPA plus 1000 mg/6 wk TU and then 1000 mg/8 wk TU plus 20 mg/d CPA (n = 8), 2 mg/d CPA (n = 8), or plus placebo (n = 8) for 32 wk. Blood samples, physical examinations, hormones, chemistry, hematology, semen analysis, and sexual/behavioral assessments were performed throughout the study. Sperm counts decreased to less than 1 million/ml in all subjects by wk 12, and 54% of them achieved azoospermia. Suppression of sperm counts was maintained until wk 44. Serum LH and FSH levels were suppressed by wk 12 of hormone administration and remained suppressed until wk 44. No significant changes in any biochemical parameters were detected at wk 44 in any group. There was a slight increase in total prostate volume to within the normal range at wk 44 that returned to baseline 1 yr after stopping hormone administration. In conclusion, TU alone or combined with lower doses of CPA maintains sperm suppression induced by higher dose CPA plus TU for 32 wk. This prototype regimen represents a promising male contraceptive regimen.

Background: The 'test and treat' strategy for Helicobacter pylori is recommended in dyspeptic patients under 55 years of age with no alarm symptoms. Reliable non-invasive tests are therefore needed. The aim of this study was to assess the pre- and post-treatment accuracy of a low dose (1 microCi [37kBq]), short collecting time [14C]-UBT (urea breath test) in diagnosing H pylori infection, examining different methods to analyse the best cut-off points., Methods: The study included 119 patients. Endoscopy and [14C]-UBT were performed in the pre- and post-treatment setting. [14C]-UBT results were expressed in three different ways: 1) the measured disintegrations per minute (dpm) at sample time, 2) the difference (D) in dpm between sample time and the dpm at T0, 3) the ratio of dpm at sample time to dpm at T0., Results: Seventy-six out of the 119 patients (63.9%; 95% CI: 54.9 to 71.9) were infected. Seventy-three (96%) patients completed the follow-up. The most accurate results in both pre- (sensitivity 95.9%; specificity 97.7%) and post-treatment (sensitivity 90.9%; specificity 100%) were obtained using the difference (D) in dpm between sample time at T0 and at T12.5., Conclusion: A low dose [14C]-UBT, with a short collecting time, is a reliable method to evaluate H. pylori infection in both the pre- and post-treatment setting.

Context: Salmonella has been identified as a causative agent of acute pancreatitis., Objective: We prospectively evaluated the frequency of acute pancreatitis, pancreatic enzyme elevation and morphological pancreatic abnormalities in patients with Salmonella infection., Subjects: Thirty consecutive patients with salmonellosis (Salmonella enterica serovar Enteritidis: n=25; Salmonella enterica serovar Typhimurium: n=5) and 30 sex- and age-matched healthy subjects were studied., Main Outcome Measures: All subjects underwent serum amylase and lipase determination and ultrasonography., Results: None of the subjects developed acute pancreatitis. Two patients (6.7%) and two controls showed serum amylase activity above the upper reference limit whereas, in five patients (16.7%) and one control subject (3.3%), the serum lipase activity appeared above the upper reference limit. Salmonella infection significantly increased serum activity of lipase (P<0.001) while it did not significantly affect serum amylase levels (P=0.204). Serum lipase activity was significantly higher in patients infected by Salmonella enterica serovar Typhimurium than in those infected by Salmonella enterica serovar Enteritidis (P=0.012). Ultrasonography did not show pancreatic abnormalities in any of the subjects., Conclusions: Our data demonstrated an elevation of serum lipase activity in gastroenteritis due to Salmonella infection, but this elevation does not seem to have clinical significance. The elevation of serum lipase seems to be particularly related to infection from Salmonella enterica serovar Typhimurium.

Introduction: An association has been found between CFTR gene mutations and chronic pancreatitis; however, there is a lack of information about the frequency of CFTR gene mutations in acute pancreatitis and in pancreatic cancer., Aim: To prospectively evaluate the prevalence of CFTR gene mutations in acute pancreatitis, chronic pancreatitis, and pancreatic cancer., Methodology: Ninety-eight consecutive patients were studied and divided into 3 groups: 34 patients with acute pancreatitis, 46 patients with chronic pancreatitis, and 18 patients with pancreatic cancer. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism., Results: Among the 98 patients studied, 12 (12.2%) had CFTR gene mutations: 2 of the 34 patients (5.9%) with acute pancreatitis, 9 of the 46 (19.6%) with chronic pancreatitis, and 1 of the 18 (5.6%) with pancreatic cancer. All the mutations were found in heterozygosis (2 DeltaF508, 1 W1282X, and 9 T5 allele)., Conclusion: Our prospective study adds further information about the frequency of CFTR mutations in patients with a single episode of acute pancreatitis. Furthermore, our results suggest an association of CFTR gene mutations with chronic alcoholic pancreatitis and emphasize the need for a multicenter study, possibly multinational, to conclusively establish the role of CFTR mutations as a genetic susceptibility factor for this disease.

Background: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate., Aim: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis., Methods: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis., Results: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002)., Conclusions: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.

Introduction: The rate of complications after endoscopic sphincterotomy (ES) is about 10%, and early complications have been reported in 20% of patients considered unfit for surgery., Aim: To evaluate the early and long-term results of endoscopic intervention in relation to the anesthesiological risk for 87 patients with acute biliary pancreatitis., Methodology: All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and were evaluated according to the American Society of Anesthesiology (ASA) criteria immediately before the operative procedure. Patients' ASA scores were as follows: 49.4%, ASA 2; 29.9%, ASA 3; and 20.7%, ASA 4., Results: The severity of acute pancreatitis was positively related to the anesthesiological grade (p = 0.014). Six patients (6.9%) had complications related to the endoscopic procedure. There was no significant relationship between the frequency of biliopancreatic complications during the follow-up (23/84, 27.4%) and the ASA grade. The frequency of cholecystectomy was inversely related to the ASA grade (p = 0.003). Seven patients (8.3%) died during the follow-up period: multivariate analysis showed that the ASA grade (odds ratio [OR], 10.9; 95% confidence interval [CI], 1.2-96.6; p = 0.001) and age (OR, 1.1; 95% CI, 1.0-1.3; p = 0.037) were significantly related to survival., Conclusions: Endoscopic treatment is safe and effective in patients at high anesthesiological risk with acute pancreatitis, and survival is significantly related to the ASA grade.

Objective: M2-pyruvate kinase isoenzyme (M2-PK) is expressed by undifferentiated or proliferating tissue. The aim of the study was to establish the diagnostic role of tumor M2-PK (TM2-PK) in patients with neuroendocrine tumors and to compare its diagnostic value with that of chromogranin A (CgA) which is well-established., Materials and Methods: Forty-nine patients with proven neuroendocrine tumors were divided as follows: subgroup A (17 patients in whom the tumor was surgically removed), subgroup B (9 patients with the neoplasm without metastases) and subgroup C (23 patients with tumor and distant metastases). Twenty-four healthy subjects were also studied as controls. Plasma TM2-PK and CgA were measured using ELISA techniques., Results: TM2-PK concentrations (cut-off value 5.6 U/mL) were abnormally high in 25.0% of the healthy subjects, in 41.2% of the patients of subgroup A, in 66.7% of those of subgroup B and in 78.3% of those of subgroup C. CgA concentrations (cut-off value 5.0 U/L) were normal in all healthy subjects, whereas they were abnormally high in 76.5% of the patients of subgroup A, in 88.9% of those of subgroup B and in 95.7% of those of subgroup C., Conclusion: Since TM2-PK has a sensitivity similar to that of CgA while its specificity is significantly lower (p = 0.031), it seems of limited value in detecting neuroendocrine tumors.

Background: The CD69 antigen is an indicator of early lymphocyte activation., Goals: To evaluate the early activation of peripheral lymphocytes T, B, and NK in patients with acute pancreatitis in comparison with patients with acute abdomen of nonpancreatic origin., Study: Thirty patients with acute pancreatitis were studied; 20 of them had the mild form of the disease and 10 had the severe form. Thirty patients with nonpancreatic acute abdomen were used as controls. All patients were enrolled within 48 hours of the onset of pain. In all patients, leukocytes and total lymphocyte and lymphocyte subset counts (CD4+, CD8+, CD56+, CD19+, CD4+CD69+, CD8+CD69+, CD56+CD69+, CD19+CD69+) were determined upon hospital admission., Results: The percentage of total lymphocytes was significantly lower in acute pancreatitis patients than in those with nonpancreatic acute abdomen (P = 0.014); patients with severe pancreatitis had a percentage of total lymphocytes significantly lower when compared with patients with mild pancreatitis (P < 0.001). The CD19+CD69+ count was significantly lower in patients with severe pancreatitis (24.6 +/- 14.6%) than in patients with mild pancreatitis (46.7 +/- 16.5%; = 0.006). The counts of the other lymphocyte subsets were not statistically different between patients with acute pancreatitis and those with nonpancreatic acute abdomen, as well as between patients with mild and severe acute pancreatitis., Conclusions: Patients with severe pancreatitis show impaired early activation of peripheral CD19+ cells.

In this study we compared the effects of high-dose and low-dose testosterone enanthate (TE) administered with the same dose of cyproterone acetate (CPA). Eighteen men aged 21-45 were treated with CPA 5 mg/day and with TE 100 mg/week (n = 9; CPA-5-100) or TE 200 mg/week (n = 9; CPA-5-200) for 16 weeks. Semen analyses were performed every 2 weeks; physical examination and chemistry, hematology, gonadotropin, and testosterone measurements were performed every 4 weeks. At week 16 of treatment, sperm counts were significantly more suppressed in the CPA-5-100 group than in the CPA-5-200 group. Sperm counts returned to baseline in all subjects after hormone administration ceased. No difference in gonadotropin levels was found at any time between the 2 groups. During the treatment phase, testosterone levels were significantly higher in the CPA-5-200 group than in the CPA-5-100 group. The present study confirms that CPA/TE administration induces profound sperm suppression. An increase in the dose of androgen resulted in less profound sperm suppression despite no difference in gonadotropin suppression. These data suggest that high testosterone levels can maintain sperm production in men.

Background: There is a lack of data concerning pancreatic involvement during shock., Aim: To evaluate possible pancreatic alterations in the early phase of shock., Setting: Twelve consecutive patients with shock were studied within 2 hours from the onset of illness. Seven patients died during the hospital stay: 3 within 4 hours from admission, 3 within 4-8 hours and 1 within 12 hours., Main Outcome Measures: Amylase, lipase, C-reactive protein, amyloid A, interleukin 6, procalcitonin and vascular cell adhesion molecule-1 serum concentrations were determined on admission and 4, 8, and 12 hours afterward. All patients underwent imaging studies of the pancreas., Results: None of the patients developed clinical signs or morphological alterations compatible with acute pancreatitis. Serum amylase levels were above the upper reference limit in 7 patients (58.3%) and serum lipase levels in 2 patients (16.7%; P=0.062). There were no significant differences found between survivors and non-survivors in the serum concentrations of all the proteins studied., Conclusions: In patients with shock, amylase seems to be more frequently elevated than lipase. None of the patients showed pancreatic alterations at imaging techniques.

Objective: For the long term maintenance treatment of reflux esophagitis several strategies have been proposed with the aim of reducing the daily dosage or the frequency of drug administration. However, the available clinical studies are scarce and are often not controlled or conducted on a reduced number of cases. We aimed to compare the efficacy of two doses of lansoprazole (15 mg once daily and 30 mg on alternate days) in maintaining endoscopic healing and symptom relief over a 6-month period., Methods: One hundred thirty-seven patients with Savary-Miller grades I-III reflux esophagitis healed after an 8-wk treatment with lansoprazole (30 mg daily) were divided into two main groups for a 6-month maintenance therapy period: lansoprazole, 15 mg once daily (group 15qd) and lansoprazole, 30 mg on alternate days (group 30qod). These two main groups were further subdivided according to the time of drug administration; morning (15qdm and 30qodm) and evening (15qde and 30qode). Each patient underwent esophagogastroduodenoscopy before entry into the study, after 8 wk of acute therapy, and after 6 months of maintenance therapy; 24-h esophageal-gastric pH monitoring was performed at baseline and during the last week of maintenance therapy., Results: At the end of the maintenance period the recurrence of esophagitis was observed in 12.1% of group 15qd patients and in 19.0% of group 30qod patients, without significant differences between the two groups. The frequency of patients without reflux symptoms after the 6-month period was the same for both groups; however, a significant increase of heartburn was observed in group 30qod patients (from 12.1% to 28.6%, p = 0.007). The time of drug administration (morning and evening) had no influence on the outcome of treatment. Both regimens significantly reduced esophageal acid exposure time and increased the median 24-h gastric pH., Conclusions: Both long term lansoprazole regimens are equally effective in preventing the recurrence of esophagitis, independent of the modality of drug administration. The daily administration seems to have a better effect on the prevention of symptom recurrence.

Aim: To evaluate the clinical, morphological and aetiological aspects of acute pancreatitis in children in Italy., Patients: The hospital records of 50 consecutive patients with acute pancreatitis observed in 5 Italian Pediatric Departments were reviewed., Results: A total of 25 males and 25 females (median age 10.5 years, range 2-17) were studied. Of these patients, 48 (96%) had abdominal pain. The pancreatitis was associated with biliary disease in 10 patients (20%); it was due to viral infection in 6 patients (12%), pancreatic duct abnormalities in 4 (8%, familial chronic pancreatitis in 3 (6%), trauma in 5 (10%) and other causes in 5 (10%); the pancreatitis was of unknown origin in 17 patients (34%). Previous attacks of the disease had occurred in 14 patients. A diagnosis of mild pancreatitis was made in 41 patients (82%) and of severe disease in 9 (18%). One patient with severe pancreatitis died from multiorgan failure. Patients with severe pancreatitis had significantly higher serum concentrations of C-reactive protein than patients with mild pancreatitis. Hospital stay was similar for patients with the mild form and those with the severe form of the disease., Conclusions: In Italian children, acute pancreatitis is of unknown origin in about one-third of the children and is recurrent in 28% of the cases. The disease is severe in 18% of the cases.

Androgen-progestin combinations are promising male contraceptive regimens. Optimization of these regimens includes the development of new progestins with more favorable biological properties. In this context we tested the effects of the progestin dienogest (DNG) on reproductive hormones and metabolic parameters in men. After a 3-wk control period, 25 men were randomly assigned to receive daily doses of 2, 5, or 10 mg DNG or placebo and 10 mg cyproterone acetate for 21 d (n = 5 subjects/group). Subjects were followed for 2 wk after cessation of hormone administration. Weekly blood samples, physical examinations, hormone and chemistry measurements, semen analysis, and sexual/behavioral assessments were performed. These parameters were compared among study groups and within each group at different time points throughout the study periods. DNG and cyproterone acetate administration resulted in profound suppression of gonadotropins and T with no change in SHBG levels. No adverse effects were detected in any subject. Hormone levels returned to baseline after stopping hormone intake. DNG is a potent suppressor of gonadotropins and T in men and does not induce adverse effects over a 21-d administration. DNG is a promising progestin to be used in clinical trials for male contraception.

This study analyses the relationships between body fat distribution and socioeconomic and psychological factors in a cohort of 426 healthy middle-aged women living in Virgilio, Mantua (Northern Italy). The information concerning their occupational, social and psychological conditions and smoking habits were obtained by means of questionnaires. Psychological factors were investigated using the Italian version of the Illness Behaviour Questionnaire and the Symptom Questionnaire. Anthropometric measurements, body mass index (BMI) (kg/m2), waist/hip ratio (WHR) and clinical/hormonal menopausal status were also collected for each subject. The women reported significantly higher or lower psychological factor scores (symptoms of conversion: p=0.005; perception of disease: p=-0.018; denial: p=0.021; hostility: p=0.57; and laxity: p=0.047) as their WHR increased, thus indicating some concern about their health. In a multiple regression model, their WHR and waist circumference (W) significantly correlated with symptoms of conversion (p=0.005 and p=0.029), and W was also significantly related to the perception of disease (p=0.043). There was a significant inverse correlation between the WHR and educational level (p<0.001). The prevalence of partners who were entrepreneurs or self-employed also decreased as WHR increased (p<0.001). Furthermore, the number of women living in the centre of town significantly diminished, whereas those living in the suburbs or in the country significantly increased (p=0.005). However, using age, BMI and menopausal status as covariates, only the partner's work significantly and negatively correlated with the WHR (p=0.029). These results are consistent with the hypothesis that psychological and socio-economic handicaps are associated with a higher prevalence of abdominal fatness in middle-aged women living in Northern Italy

Background: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD)., Methods: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%)., Results: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence., Conclusions: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Objective: Urine trypsinogen-2 has been suggested as a marker of damage due to acute pancreatitis. Our aim was to assess the time-course and the clinical value of this test in acute pancreatitis., Methods: A urine trypsinogen-2 dipstick test was performed on 30 patients with acute pancreatitis upon admission to the emergency room, as well as on 30 patients with non-pancreatic acute abdominal pain, and in 30 healthy subjects., Results: In 53.3% of the patients with acute pancreatitis the dipstick test showed abnormal urine trypsinogen-2 whereas this test gave negative results in all patients with non-pancreatic acute abdomen and in all healthy subjects. Patients with severe acute pancreatitis had a frequency of abnormal results of urine trypsinogen-2 (8/9, 88.9%; 95% CI, 51.8-99.7%) significantly higher (P = 0.031) than those with the mild disease (8/21, 38.1%; 95% CI, 18.1 -61.6%), while no significant differences were found in the urine trypsinogen-2 results between patients with biliary acute pancreatitis and those with non-biliary acute pancreatitis. Regarding the time-course of urine trypsinogen-2, there were no significant differences during the three days of the study., Conclusions: The specificity of urine trypsinogen-2 in the diagnosis of acute pancreatitis is good however its sensitivity is low.

Objective: To assess the sensitivity and specificity of the serum carboxypeptidase B activation peptide in diagnosing and determining the severity of acute pancreatitis., Patients: Twenty consecutive patients with acute pancreatitis were studied on admission to the Emergency Room: 11 patients had mild pancreatitis, and 9 patients, severe pancreatitis. Twenty consecutive patients with non-pancreatic acute abdomen and 20 healthy subjects were also studied., Main Outcome Measures: Serum carboxypeptidase B activation peptide was determined using radioimmunoassay., Results: Nineteen of the 20 patients with acute pancreatitis (95.0%) had serum carboxypeptidase B activation peptide concentrations above the upper reference limit, whereas 1 of the 20 patients with non-pancreatic acute abdomen (5.0%) and none of the healthy subjects had serum levels of this protein above the upper reference limit. The serum carboxypeptidase B activation peptide concentrations of patients with severe acute pancreatitis were significantly higher than those of patients with mild acute pancreatitis on the 2(nd) (P=0.044) and 3(rd) days (P=0.028) of the study. The overall sensitivity and specificity of carboxypeptidase B activation peptide in assessing the severity of acute pancreatitis were 84.6% and 59.4%, respectively., Conclusions: Serum carboxypeptidase B activation peptide may be used simultaneously both to diagnosis and assess the severity of acute pancreatitis on admission to the Emergency Room.

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)

Amyloid A (SAA) and procalcitonin (PCT) have been reported as useful indicators of inflammation. Our aim was to assess the utility of SAA and PCT in establishing the severity of acute pancreatitis in comparison to C-reactive protein (CRP): Thirty-one patients with acute pancreatitis enrolled within 24 hr from the onset of pain and 31 healthy subjects were studied. Nineteen patients had mild acute pancreatitis, and 12 had severe pancreatitis. Serum SAA, PCT, and CRP were measured in all subjects at admission and, in acute pancreatitis patients, during the following five days. Patients with acute pancreatitis had serum concentrations of SAA, PCT, and CRP significantly higher (P < 0.001) than those of healthy subjects during the entire study period. Using cutoff values ranging from 240 to 250 mg/liter for SAA, from 0.252 to 0.255 ng/ml for PCT, and from 12.8 to 12.9 mg/dl for CRP, the sensitivity (calculated on patients with severe pancreatitis), the specificity (calculated on patients with mild pancreatitis), and the efficiency (calculated as the percentage of correct classifications) were 76.8%, 69.3%, and 72.4% for SAA; 21.7%, 83.2%, and 58.2% for PCT; and 60.9%, 89.1%, and 77.6% for CRP. In conclusion, the sensitivity of SAA is significantly higher than that of PCT and CRP in assessing the severity of pancreatitis, whereas PCT and CRP had a specificity significantly higher than SAA. The accuracy and efficiency were similar for SAA and CRP, and both these markers had an accuracy and efficiency significantly higher than those of PCT.

The aim of this study was to evaluate the incidence, radiographic appearance, time of onset, outcome and risk factors of non-infectious and infectious pulmonary complications following liver transplantation. Chest X-ray features of 300 consecutive patients who had undergone 333 liver transplants over an 11-year period were analysed: the type of pulmonary complication, the infecting pathogens and the mean time of their occurrence are described. The main risk factors for lung infections were quantified through univariate and multivariate statistical analysis. Non-infectious pulmonary abnormalities (atelectasis and/or pleural effusion: 86.7%) and pulmonary oedema (44.7%) appeared during the first postoperative week. Infectious pneumonia was observed in 13.7%, with a mortality of 36.6%. Bacterial and viral pneumonia made up the bulk of infections (63.4 and 29.3%, respectively) followed by fungal infiltrates (24.4 %). A fairly good correlation between radiological chest X-ray pattern, time of onset and the cultured microorganisms has been observed in all cases. In multivariate analysis, persistent non-infectious abnormalities and pulmonary oedema were identified as the major independent predictors of posttransplant pneumonia, followed by prolonged assisted mechanical ventilation and traditional caval anastomosis. A "pneumonia-risk score" was calculated: low-risk score ( < 2.25) predicts 2.7% of probability of the onset of infections compared with 28.7% of high-risk (> 3.30) population. The "pneumonia-risk score" identifies a specific group of patients in whom closer radiographic monitoring is recommended. In addition, a highly significant correlation (p < 0.001) was observed between pneumonia-risk score and the expected survival, thus confirming pulmonary infections as a major cause of death in OLT recipients.

Background and Purpose: Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal weight. We tested the hypothesis that there is an association between nonalcoholic fatty liver disease and insulin resistance that is independent of diabetes and obesity., Subjects and Methods: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "bright liver" on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex., Results: Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70], fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/ liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects did not change the results., Conclusion: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.

Aims/background: Current therapy for chronic hepatitis C virus (HCV) infection is based on the administration of interferon alpha (IFN) alone or in combination with other anti-viral agents. However, such therapy is effective in only a minority of selected patients. Long-term ursodeoxycholic acid (UDCA) treatment has been reported to improve liver function and structure especially in cholestatic disorders. We investigated the effect of long-term UDCA treatment on liver function in respect to the severity of chronic liver disease and HCV genotypes., Methods: Forty-five patients with non-cholestatic laparoscopy-biopsy proven HCV-associated chronic hepatitis (n=16) or cirrhosis (n=29) who had not responded to, or were unsuitable for IFN, were randomly assigned to receive UDCA (600 mg/day; n=23) or no therapy (n=22) for 12 months. At entry, all patients were evaluated by means of conventional and quantitative liver function tests (LFTs), including galactose elimination capacity and antipyrine clearance, HCV antibodies, HCV-RNA and HCV genotypes. LFTs were measured at 6 and at 12 months, whereas HCV-RNA was determined again after treatment., Results: Baseline characteristics were comparable in the two study groups. Long-term UDCA therapy was well tolerated. Based on the analysis of variance, there was a significant decrease in serum transaminase, LDH and GGT levels in UDCA treated patients. By contrast, the activities of these enzymes increased in untreated patients, with AST levels reaching statistical significance only. Statistical analysis also showed that the improvement in biochemical markers was more pronounced in UDCA treated patients with liver cirrhosis than in those with chronic hepatitis but was similar in patients with HCV genotype 1b and non-1b. However, HCV-RNA was positive in all patients after treatment. Quantitative LFTs remained, on average, stable over the 12 months of the trial in all groups., Conclusions: Long-term UDCA treatment is well tolerated in patients with HCV-associated chronic liver disease. The effect appears to be greater in cirrhotics than in patients with chronic hepatitis but is independent of HCV genotypes. Thus, long-term UDCA treatment, despite the absence of an anti-viral effect, seems beneficial in reducing disease activity in patients with chronic hepatitis or cirrhosis who are unsuitable for IFN therapy.

Background: There are no systems for the rapid diagnosis and prognosis of acute pancreatitis in the Emergency Department. Our aim was to evaluate whether the combined use of serum lipase and interleukin-6 or serum lipase and C-reactive protein is able to simultaneously establish both the diagnosis and the prognosis of acute pancreatitis., Methods: Eighty patients with acute abdomen were studied on admission to the Emergency Room. Forty patients had nonpancreatic acute abdomen, and 40 had acute pancreatitis (25 had mild acute pancreatitis and 15 had severe pancreatitis). Forty healthy subjects comparable for sex and age were also studied as controls. Lipase, interleukin-6, and C-reactive protein were determined on serum in all subjects., Results: Using lipase to discriminate between patients with nonpancreatic acute abdomen and patients with acute pancreatitis (cutoff values ranging from 419 to 520 U/L), one patient with acute pancreatitis was not identified correctly. To discriminate between patients with severe acute pancreatitis and those with mild pancreatitis in the remaining 39 patients, interleukin-6 (cutoff value, <3.7 microgram/L) had a sensitivity of 100% (15 of 15) and a specificity of 83% (20 of 24); 75 of 80 (94%) patients were classified correctly. C-reactive protein (cutoff values ranging from 6 to 7 mg/L) showed a lower prognostic efficiency than interleukin-6: sensitivity of 87% (13 of 15) and specificity of 46% (11 of 24). Sixty-four of 80 patients (80%) were classified correctly. The area under the ROC curve for interleukin-6 (0.911 +/- 0.049) was significantly (P = 0.013) greater than that for C-reactive protein (0.685 +/- 0.090)., Conclusion: The combined use of serum lipase and interleukin-6 is useful in simultaneously establishing both the diagnosis and the prognosis of acute pancreatitis.

Background: Helicobacter pylori induces histologic inflammation of mucosa variably correlated to different macroscopic features. Recent studies highlight that the presence of Helicobacter pylori could be assessed on the basis of the macroscopic pattern only, in particular nodularity. The present prospective study has correlated this and other endoscopic features, defined by Sydney classification of gastritis, both to Helicobacter pylori presence and histological patterns., Results: Out of 532 patients, 364 were evaluable. The prevalence of Helicobacter pylori was 51.1% with a different distribution between the endoscopic features. Nodularity showed the highest positive predictive value in detecting the Helicobacter pylori presence (69.9%). The histological findings were: normal 26.9%, non atrophic gastritis 55.2%, atrophic gastritis 17.9%. There was a significant difference between abnormal endoscopic features in detecting the histologic gastritis, with endoscopic atrophy and nodularity showing the highest positive predictive value which reaches 96.7% and 91.8%, respectively. Helicobacter pylori infection and histologic gastritis were also present in 30.9% and 41.8%, respectively, of endoscopically normal subjects. Multivariate analysis has strictly correlated age with all abnormal endoscopic features, metaplasia with endoscopic atrophy, and chronic inflammation (gastritis) with nodularity., Conclusions: The single endoscopic features are poorly correlated with histologic changes and Helicobacter pylori status. Biopsies are mandatory in all cases. The causes of the different macroscopic findings are not yet fully understood.

Objective: Little is known about the natural history of polycystic ovary syndrome (PCOS), although preliminary data indicate that affected women are more susceptible than the general population to diabetes and cardiovascular diseases at post-menopausal ages. The aim of this study was to follow-up all main features of the metabolic syndrome in a group of young women with PCOS and to investigate the long-term effects on metabolism and body composition of oestrogen-progestagen (OP) compounds, which are frequently used in these women to treat hyperandrogenism and related clinical features., Design: Long-term follow-up study., Subjects and Methods: Thirty-seven women with PCOS were re-evaluated 10.3 +/- 0.8 years (range 6-18 years) after their first assessments (age: before 19.8 +/- 4.9 years; after 29.9 +/- 4.4 years). When first examined, women were instructed to follow a hypocaloric diet if they were obese plus OP, if they agreed to such treatment. Main anthropometric parameters, basal sex hormones and lipids, fasting and glucose-stimulated glucose and insulin levels and several clinical data were recorded before and after follow-up., Results: In the whole group of women with PCOS we found no changes in body weight and fat mass, whereas both the waist-to-hip ratio and the waist-to-thigh ratio were significantly reduced. No significant changes occurred in mean fasting and glucose-stimulated glucose and insulin concentrations, whereas a significant increase in high-density lipoprotein-cholesterol was found. No significant changes occurred in testosterone levels. During the follow-up period 16 women took OP for an average of 97 +/- 18 months (range 12-180 months) (OP-users) whereas 21 women never took OP (non-OP-users). All OP-users were still taking OP when re-evaluated at the follow-up examination. With respect to baseline values, body mass index was higher in non-OP-users than in their counterparts. Waist circumference (P < 0.025), the waist-to-hip (P < 0.05) and the waist-to-thigh (P < 0.01) ratios decreased significantly only in the OP-users. In addition, percentage changes in waist circumference (P < 0.05) and waist-to-hip ratio (P < 0.05) during the follow-up period were significantly different between the groups. Glucose tolerance (as area under the curve (AUC)) improved (P < 0.05) in OP-users but not in non-OP-users. Moreover, compared to baseline values, basal insulin levels were significantly (P < 0.01) reduced in OP-users but not in non-OP-users. On the contrary, no significant change was found in insulinAUC in the former, whereas it significantly increased (P < 0.05) in the latter. Accordingly, fasting C-peptide decreased (P < 0.05) in OP-users, whereas both fasting (P < 0.01) and stimulated (P < 0.01) C-peptide significantly increased in non-OP-users. Changes in fasting or stimulated insulin and C-peptide in non-OP-users were not associated with parallel changes in testosterone levels. Total cholesterol and triglycerides did not change in either group, but HDL-cholesterol increased (P < 0.05) only in OP-users. Sex hormone-binding globulin concentrations increased significantly (P < 0.01) in OP-users, without any significant change in non-OP-users. Testosterone concentrations did not change significantly in either group, but the testosterone: SHBG ratio significantly decreased in OP-users (P < 0.05) but not in the non-OP-users. Among the clinical features, acanthosis nigricans significantly (P < 0.01) worsened in non-OP-users but not in the OP-users, without any significant change in the hirsutism and acne scores. Pregnancy rates during the follow-up were similar in both groups., Conclusions: These data indicate that hyperinsulinaemia and insulin resistance tended to worsen spontaneously in women with PCOS, without any worsening of the hyperandrogenism. Long-term oestrogen-progestagen treatment countered this tendency, probably because it improved the pattern of body fat distribution, by reducing abdominal fat depots.

Serum amylase and lipase concentrations were determined in 78 patients with chronic liver diseases [26 chronic active hepatitis (CAH) and 52 liver cirrhosis] and in 15 healthy subjects. Pancreatic isoamylase concentrations and macroamylase complexes were assayed in hyperamylasemic sera. Serum amylase levels were abnormally elevated in 27 patients (35%; 22 liver cirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 liver cirrhosis, 1 CAH). In 9 of the 27 hyperamylasemic patients, the hyperamylasemia was of pancreatic type. Macroamylasemic complexes were not detected in hyperamylasemic sera. Patients with liver cirrhosis had serum levels of amylase and lipase significantly higher than both the healthy subjects and the patients with CAH, while no significant differences were found in serum levels of these enzymes in patients with CAH as compared to the healthy subjects. A decreased liver metabolism of serum amylase and lipase in patients with chronic infective liver disease, especially in those having liver cirrhosis, may lead to an accumulation of these enzymes in the blood.

In the Emergency Department it is mandatory to establish the diagnosis and the prognosis of acute pancreatitis as soon as possible. To evaluate whether the association of serum lipase either with serum beta2-microglobulin or with C-reactive protein allows simultaneously to establish the diagnosis and the prognosis of acute pancreatitis, 96 patients with acute abdomen were studied. Fifty-eight patients had non-pancreatic acute abdomen and the remaining 38 had acute pancreatitis: 23 mild acute pancreatitis, and 15 severe acute pancreatitis. Forty healthy subjects were studied as controls. Lipase, beta2-microglobulin and C-reactive protein were determined in the serum of all subjects, using commercial kits. One patient with acute pancreatitis was not correctly classified when lipase was used to discriminate between patients with non-pancreatic acute abdomen and those with acute pancreatitis. For the discrimination of patients with severe acute pancreatitis from those with the mild form of the disease in the remaining 37 acute pancreatitis patients, beta2-microglobulin had a sensitivity of 53.3 %, specificity of 81.8%, and prognostic accuracy of 70.3 % (27 of the 37 patients correctly classified); 87.5 % of the 96 cases were correctly classified. C-reactive protein showed a lower prognostic accuracy than beta2-microglobulin: sensitivity 86.7%, specificity 45.5%, accuracy 62.2 %; 84.4 % of the cases were correctly classified. Using the polychotomous logistic regression analysis we found the same accuracy in discriminating between patients with acute pancreatitis and those with non-pancreatic acute abdomen (99.0%) but a lower accuracy (54.1%) between patients with severe acute pancreatitis and those with the mild form of the disease. Our study shows that the association of serum lipase with beta2-microglobulin or with C-reactive protein is not useful in simultaneously establishing the diagnosis and prognosis of acute pancreatitis.

Aim: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria., Methods: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored., Results: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01)., Conclusions: Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

Background/aims: To correlate the severity of acute pancreatitis with the etiology, age and sex of the patients., Methodology: 158 consecutive acute pancreatitis patients (92 males, 66 females; mean age 59.7+/-18.1 years; mean+/-SD) who were admitted to our Emergency Department between January 1991 and March 1995 were included in this study. The diagnosis of acute pancreatitis was made on the basis of the characteristic abdominal pain associated with hyperamylasemia and hyperlipasemia and was further confirmed by ultrasonography and/or computed tomography findings., Results: Acute pancreatitis was associated with biliary disease in 112 patients (70.9%), due to alcohol abuse in 26 patients (16.5%), due to other causes in 8 (5.1%), and was of unknown origin in 12 (7.6%). On the basis of the Atlanta criteria, 110 patients (69.6%) were diagnosed as having mild acute pancreatitis and 48 (30.4%) as having the severe form of the disease. The age of the males was significantly lower than that of females; the age of patients with biliary pancreatitis was significantly higher than that of the overall population, whereas the age of patients with acute pancreatitis due to other causes was significantly lower. A significantly higher frequency of acute biliary pancreatitis was found in females (97.0%) as compared to males (52.2%), while alcoholic pancreatitis and pancreatitis due to other causes was present only in males (28.3% and 8.7%, respectively)., Conclusions: An age greater than 55 years, the male sex, pancreatitis of unknown origin and alcoholic pancreatitis were positively associated with the severity of the disease.

To investigate whether obese female subjects with abdominal obesity may have adrenal androgen hypersecretion, we examined two groups of women with abdominal (n = 12) and peripheral (n = 13) obesity (defined by body mass index and waist-to-hip ratio) and a group of seven healthy normal-weight women. All subjects underwent the following protocol study that included a) baseline determination of major adrenal androgens, b) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microg/Kg BW, e.v.), at 90 min intervals, with blood samples taken for cortisol and androgens, c) an oral glucose tolerance test, performed by administering glucose (75 gr), with blood samples taken for glucose and insulin determination. Each woman also underwent a control saline study. We then investigated the relationships between basal and stimulated androgen levels, body weight and fat distribution and fasting and stimulated insulin levels. Although basal cortisol levels were similar, their increase (as AUC) after the ACTH test was higher in women with abdominal obesity than in the other groups. On the contrary, there were no significant differences in basal and stimulated serum levels of dehydroepiandrosterone, androstenedione and 17-hydroxyprogesterone among the three groups. Fasting and stimulated (as AUC) insulin levels were significantly higher (p < 0.05) in women with abdominal obesity than in those with peripheral obesity and controls. No significant correlation was present between basal and stimulated androgen levels and body mass index, the waist-to-hip ratio or basal and stimulated cortisol values. Therefore, our data indicate that adrenal androgen secretion following low-dose ACTH administration in premenopausal women does not seem to be a function of body fat mass, fat distribution and insulin levels, nor does it correlate with the capacity of the adrenal glands to secrete cortisol in both basal and stimulated conditions.

Background: The aim of as study was to ascertain whether the association of interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in ameliorating liver parameters than interferon (IFN) alone in patients with chronic hepatitis C., Methods: Forty-one chronic hepatitis C patients, who had at least twice the normal value of one transaminase, were randomly assigned to treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day. IFN therapy was terminated 6 months later and the responders (normalized transaminases) of both groups were treated with UDCA alone for a further 12 months., Results: In the IFN + UDCA group there were 2 drop-outs from therapy and 11 responders, while in the IFN group they were, respectively, 3 and 10. Transaminases normalized after the first month of treatment in 7/11 responders with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95; p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11 responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by PCR. The total Knodell histological score decreased more in the IFN+UDCA than in the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD)., Conclusions: The administration of UDCA determine an earlier normalization-time of transaminases in the patients responders to IFN therapy and could be useful to reduce the relapse into disease after the IFN therapy.

Background: An impaired lipid metabolism is often found in patients with chronic liver diseases. Unfortunately, few studies are available concerning serum lipid and lipoprotein levels in patients with liver cirrhosis and chronic active hepatitis (CAH)., Objectives: To evaluate low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and total cholesterol serum levels in patients with cirrhosis and CAH and control patients and to relate the findings to the severity of the cirrhosis (Child classification)., Methods: We measured the serum lipid pattern in 34 consecutive patients with liver cirrhosis (15 men and 19 women; mean [+/-SD] age, 55 +/- 14 years; Child classes: 14 in A, 9 in B, 11 in C; patients with biliary cirrhosis were excluded), 34 patients with CAH, and 34 control patients. The 3 groups were matched for sex and age. Total serum, HDL cholesterol, and triglyceride levels were measured by enzymatic methods; serum LDL and VLDL levels were calculated., Results: In patients with cirrhosis, there was a significant decrease in LDL, HDL, and total cholesterol serum levels compared with both the patients with CAH and the control patients, while the VLDL cholesterol level in patients with cirrhosis was significantly lower compared with the control patients alone. A significant decrease in total cholesterol levels was also observed in the CAH group when compared with the control patients. In patients with cirrhosis, levels of LDL, HDL, and total serum cholesterol were progressively lower when comparing patients in Child class A with patients in class C., Conclusions: In this study, the striking decrease in the level of serum LDL cholesterol in patients with liver disease was related to the increasing severity of the disease. Accordingly, the assessment of the serum LDL cholesterol level is important for an effective treatment and prognostic evaluation of patients with chronic liver disease.

Background/aims: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis., Methods: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period., Results: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups., Conclusions: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Diagnostic reproducibility and accuracy in evaluating cervical/vaginal smears were the focus of this study concerning intralaboratory quality control. A set of 120 cytological samples was evaluated by 15 cytopathologists whose experience ranged from 3-29 yr. The study report form was based on the 1988 Bethesda System. Intercytologist reproducibility (with respect to sample adequacy, epithelial cell abnormalities, and presence of cellular changes associated with HPV, Human Papilloma virus) was evaluated using the Kappa statistic. Poor reproducibility in defining sample adequacy was observed (K = 0.24). The agreement on epithelial cell abnormality definition was good (K = 0.64); the lowest reproducibility was observed for High-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia HSIL/CIN II (specific K = 0.37) and Atypical cells of undetermined significance ACUS (specific K = 0.44). The agreement in detecting cellular changes associated with HPV was fair (K = 0.49). Diagnostic accuracy for epithelial cell abnormalities, assessed by comparison with a consensus reference diagnosis, was good (K = 0.74).

Conclusion: In acute pancreatitis (AP), the peripheral blood analysis, including reticulocytes (RC) and RC fractions, and its relationship to the changes of the levels of the soluble interleukin 2 receptor (sIL-2R) can provide useful information about the involvement of the immunoinflammatory system in AP and can indicate the severity of the disease., Background: In the disease clinical assessment, we correlated the sIL-2R serum levels to the peripheral blood components (including RC and RC fractions) to serum albumin and C-reactive protein (CRP) during AP., Methods: In 21 patients with AP, sIL-2R, the total and differential white blood cell (WBC) counts, red blood cell (RBC) counts, RC, RC fractions, hemoglobin (Hb), hematocrit (Ht), platelets (PLT), albumin, and CRP were evaluated from the onset to the sixth day of illness., Results: sIL-2R increased in all the patients. The increase was directly related to eosinophils, monocytes, and to middle-aged (MFR) RC, and inversely related to neutrophils and the old (LFR) RC. MFR-RC were directly related to the total WBC count, eosinophils, and basophils, and inversely related to Hb and albumin. LFR-RC behaved in the opposite manner. CRP increased in 16 patients; this rise was directly related to WBC, RC, and MFR-RC, and inversely related to Hb, LFR-RC, and albumin. sIL-2R and CRP values were not statistically interrelated, but when the CRP levels were higher, the increase in sIL-2R was greater and more sustained.

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.

Study Objective: To establish the crude effects of danazol and gonadotropin-releasing hormone (GnRH) analogs in the management of endometriosis., Design: Prospective case-control study., Setting: Unit of the Pathophysiology of Reproduction outpatient department., Patients: Two groups of 110 women each with endometriosis (American Fertility Society score 1-3) who received danazol and GnRH analogs, and a control group who did not receive any drugs., Interventions: Women in the treatment groups received danazol 200 mg every 8 hours for 6 months, or a different GnRH agonist at standard dosages for 6 months. Laparoscopy was performed twice, at the time of diagnosis and just before the end of treatment (or no therapy for controls). Surgical treatment of the implants was performed at the second laparoscopy., Measurements and Main Results: Samples of both eutopic and ectopic endometrium were collected during both laparoscopies. Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants, and there were no significant differences between the effects (p <0.001). Fibrosis was found after 6 months of observation in the implants in one control woman (0.9%), in 20 patients (18.2%) treated with danazol (p <0.001 vs controls), and in 4 patients (3.6%) treated with GnRH agonists (NS vs controls). A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28% of women, with poor agreement (k = 0.07)., Conclusions: Fibrosis, which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium, did not appear in eutopic endometria but it was found in some endometriotic implants. Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis, but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable.

Current data regarding an association between cholelithiasis, cholecystectomy, or gastrectomy and pancreatic cancer are conflicting. We evaluated the frequency with which these factors were present in 720 patients with newly diagnosed pancreatic cancer and in 720 matched controls. All subjects were interviewed personally and in detail about their clinical history. Cholelithiasis was present in 126 patients with pancreatic cancer (17.5%) and in 95 controls (13.2%), constituting a statistically significant association (odds ratio, 1.39; 95% confidence interval, 1.04-1.86); however, considering only the patients and controls in whom the diagnosis of cholelithiasis was made more than one year before cancer diagnosis or interview, the association was no longer significant (odds ratio, 1.04; 95% confidence interval, 0.75-1.44). Cholecystectomy had been performed in 93 patients with pancreatic cancer (12.9%) and in 71 controls (9.9%). When all subjects were considered, the odds ratio was mildly, although not significantly, increased (odds ratio, 1.35; 95% confidence interval, 0.97-1.87); when only subjects who underwent cholecystectomy one year or more before the cancer diagnosis or interview were considered, the odds ratio fell to unity. Gastrectomy had been performed in 28 patients with pancreatic cancer (3.9%) and in 25 controls (3.5%); analysis revealed no significant association between these two factors (odds ratio, 1.14; 95% confidence interval, 0.64-2.05). In conclusion, our study, one of the largest on this topic, has found no evidence for an association between cholelithiasis, cholecystectomy, or gastrectomy and pancreatic cancer.

A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.

The aim of this study was to compare the sensitivity, specificity, and diagnostic accuracy of serum interleukin-6, interleukin-8, beta 2-microglobulin, and C-reactive protein in the assessment of the severity of acute pancreatitis using commercial kits for their respective assays. Thirty-eight patients with acute pancreatitis (25 men, 13 women, mean age 59 years, range 16-97) were studied; the diagnosis was based on prolonged upper abdominal pain associated with a twofold increase of serum lipase, and it was confirmed by imaging techniques. According to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The four serum markers were determined in all patients on admission, as well as daily for the following five days. On the first day of the disease, the sensitivity (calculated on patients with severe pancreatitis), specificity (calculated on patients with mild pancreatitis), and the diagnostic accuracy of these serum markers for establishing the severity of acute pancreatitis were 100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81% and 88% for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% for beta 2-microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive protein (cutoff level 11 mg/dl). The results of our study indicate that, when assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8 are better markers than beta 2-microglobulin or C-reactive protein for evaluating the severity of acute pancreatitis.

While cigarette smoking is a well-established risk factor for pancreatic cancer, the role of alcohol, coffee and tea consumption remains controversial. In view of this, and because of the limited information on possible environmental risk factors of pancreatic cancer in Italy, we carried out this study. Five hundred seventy patients with newly diagnosed pancreatic cancer and 570 controls from 14 Italian centers were studied. Using a standardized questionnaire, all were interviewed personally about their smoking habits, as well as habitual alcohol, coffee, and tea consumption throughout their lives prior to clinical onset of the disease. Details were also obtained on exposure to potential occupational carcinogens. A moderate association, statistically significant only in women (odds ratio, 2.18; 95% confidence interval, 1.30-3.68), was found between pancreatic cancer and cigarette smoking, but none was observed with alcohol or tea consumption or with any particular occupational exposure. Consumption of 1 or 2 cups of coffee per day was not associated with increased risk; 3 coffees per day increased the risk, but not significantly (odds ratio, 1.49; 95% confidence interval, 0.97-2.30); with consumption of more than 3 coffees per day the increase in risk was highly significant (odds ratio, 2.53; 95% confidence interval, 1.53-4.18). A statistically significant dose-response relationship (p < 0.001) was observed in each sex. The association between coffee use and pancreatic cancer still held after controlling for potential confounding factors such as cigarette smoking or alcohol use, and when the analysis was restricted to nonsmoking coffee drinkers. The results of this study, one of the largest of its type so far published, suggest that a causal relationship may exist between coffee consumption and pancreatic cancer.

We investigated peripheral lymphocyte subsets in 34 consecutive acute pancreatitis patients (21 males, 13 females; mean age, 57 years; range, 16-85 years) studied within 48 h of pain onset and for 5 consecutive days to understand better the immunological response during the course of the disease. The diagnosis was based on characteristic abdominal pain associated with a twofold increase in serum lipase and confirmed by imaging techniques in all patients. Acute pancreatitis was of biliary origin in 25 patients, due to alcohol abuse in 5, due to pancreas divisum in 1, and of unknown origin in 3. Fifteen patients had severe illness and 19 had mild disease. In all patients, total lymphocyte and lymphocyte subset counts were carried out on admission, as well as on the third and fifth day of hospitalization, using a flow cytometric analysis. Twenty-three patients (13 with severe illness and 10 with mild disease) also had a repeat count 1 month after recovery. Twenty-five healthy subjects and 27 patients with nonpancreatic acute abdomen comparable for sex and age were studied as controls. On the first day of the study, the leukocyte number was significantly higher in patients with acute pancreatitis and in those with nonpancreatic acute abdomen with respect to healthy subjects, whereas the number of total and CD4+, CD8+, CD3+ DR-, and CD3- DR+ lymphocytes was significantly lower in acute pancreatitis patients than in healthy subjects or in patients with nonpancreatic acute abdomen. These subject counts persisted on the third and fifth days of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The aim of this study was to assess the development of dysplasia or cancer in patients with ulcerative colitis and to determine the effectiveness of colonoscopy and biopsy follow-up in colon cancer surveillance., Methods: From 1980 to 1986, 65 patients who had ulcerative colitis for 7 years or more participated in a surveillance program of colonoscopy and biopsy. This cohort was followed until December 1992. Forty-nine patients (75.4%) had extensive colitis and 16 (24.6%) left-sided colitis. The mean disease duration was 17.2 years. Three hundred four colonoscopies were performed. During each endoscopy, random biopsies were performed., Results: Seven patients had definite dysplasia of the colorectal mucosa. Four of them had high grade lesions and underwent surgery. In all of these patients, colon cancer (3 Dukes' Stage A, 1 Dukes' Stage B) was found. No cancer was found in the other patients. Pedunculated adenomas were excised from 6 other patients during colonoscopy. When dysplasia was diagnosed, these patients were older than those who were dysplasia free, whereas the age at onset of colitis was significantly higher in the former (P < 0.01). Fifteen patients discontinued follow-up. Two of them developed colon cancer diagnosed at an advanced stage., Conclusions: Dysplasia, especially of high grade, is a marker of colon cancer risk in patients with longstanding ulcerative colitis. Intensive colonoscopy and biopsy surveillance can lead to the diagnosis of colon cancer at a potentially curable stage. In this series, older age appeared to be an additional risk factor. A careful selection of patients with ulcerative colitis seems mandatory to minimize the cost and optimize the benefit of colon cancer surveillance programs.

Background: Diabetes and pancreatic cancer are known to be associated, but the cause of the association and whether diabetes is a risk factor for pancreatic cancer remain controversial., Methods: A total of 720 patients with pancreatic cancer and 720 control patients from 14 Italian centers were enrolled in the study. All subjects were interviewed personally and in detail about their clinical history. The diagnosis of diabetes was based on criteria recommended by the American Diabetes Association., Results: One hundred sixty-four patients with pancreatic cancer (22.8 percent) and 60 controls (8.3 percent) had diabetes. In the majority of the patients with pancreatic cancer (56.1 percent), diabetes was diagnosed either concomitantly with the cancer (in 40.2 percent), or within two years before the diagnosis of cancer (in 15.9 percent). The association between the two conditions was significant (odds ratio, 3.04; 95 percent confidence interval, 2.21 to 4.17). However, when only patients with diabetes of three or more years' duration were considered, the association was no longer significant (odds ratio, 1.43; 95 percent confidence interval, 0.98 to 2.07). All the patients with pancreatic cancer whose diabetes had been diagnosed before the cancer had non-insulin-dependent diabetes; all but one of the control patients with diabetes had the non-insulin-dependent form of the disease., Conclusions: Diabetes in patients with pancreatic cancer is frequently of recent onset and is presumably caused by the tumor. Diabetes is not a risk factor for pancreatic cancer.