Can Imaging Predict Subclinical Cortisol Secretion in Patients With Adrenal Adenomas? A CT Predictive Score.

OBJECTIVE: The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion. MATERIALS AND METHODS: This is a retrospective database study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting adenoma. RESULTS: Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas. CONCLUSION: This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.

New insights in the selection and management of cancer patients applicants for ovarian tissue cryopreservation.

Ovarian tissue cryopreservation (OTC), representing a promising strategy to preserve ovarian function in cancer patients, is recommended to women younger than 35 years. This study aimed to identify endocrine and biometric parameters as additional selection criteria for OTC. One hundred and ninety-one cancer patients before chemoradiotherapy and OTC and 43 controls were investigated. Mean ± SD, median, quartiles, 5th and 95th centiles and correlations of FSH, LH, estradiol, inhibin-B, anti-Mullerian hormone (AMH), ovarian volume and antral follicle count (AFC) were assessed. Most ovarian reserve parameters presented typical variations of ovulatory menstrual cycle, except AMH and AFC showing minimal fluctuations across the menstrual cycle. The 5th centiles of AMH (0.31and 0.4 ng/mL in controls and cancer patients, respectively) and AFC (five follicular structures in both groups) could be conjectured as minimum thresholds to include patients aged <35 years in OTC; below this threshold patients of any age should be excluded from OTC. Conversely, patients with AMH and AFC above the 25th centiles (1.2-1.6 ng/mL and 9-10 follicular structures in controls and cancer patients, respectively) might be inserted in OTC regardless of age. Baseline assessment of AMH and AFC might be considered as selection criteria, in addition to chronological age, to take decision of OTC in cancer patients.

Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood.

BACKGROUND & AIMS: Acute infectious gastroenteritis increases the risk for irritable bowel syndrome (IBS) and functional dyspepsia (FD). Children are particularly vulnerable to gastroenteritis because of the immaturity of their intestinal barrier, enteric nervous system, and immune response to pathogens. We investigated whether acute gastroenteritis in early life increases the risk of IBS and FD throughout adulthood. METHODS: In 1994, we identified and monitored a single culture-proven foodborne Salmonella enteritidis outbreak that involved 1811 patients (mostly pediatric) in Bologna, Italy. Clinical data were collected and a prospective, controlled, cohort study was designed. Long-term effects were assessed by mailing a questionnaire to 757 subjects 16 years after the outbreak (when all of the children were adults). We randomly selected a cohort of 250 adults exposed to Salmonella as children, all 127 individuals exposed as adults, and a cohort of nonexposed participants matched for number, age, sex, and area of residence (controls). RESULTS: Among 198 exposed participants, 64 reported FD (32.3%), compared with 51 of 188 controls (27.1%; P = .268). Among 204 exposed participants, 75 reported having IBS (36.8%) compared with 44 of 189 controls (23.3%; P = .004). The odds ratio for IBS among people exposed to the Salmonella was 1.92 (95% confidence interval: 1.23-2.98). The prevalence of IBS was higher in individuals exposed Salmonella as children than in controls (35.3% vs 20.5%; P = .008), but not in individuals exposed as adults, compared with controls. After multivariate logistic regression, post-infectious IBS was independently associated with anxiety and FD. CONCLUSIONS: Based on data collected from a single culture-proven foodborne Salmonella enteritidis outbreak in 1994, Salmonella-induced gastroenteritis during childhood (but not adulthood) is a risk factor for IBS.

Plasma concentrations of angiogenetic factors and angiogenetic inhibitors in patients with ductal pancreatic neoplasms. A pilot study.

BACKGROUND: The aim of the study was to evaluate the circulating concentrations of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor-D (VEGF-D) and endostatin in patients with intraductal papillary mucinous neoplasm (IPMN), and in those with ductal adenocarcinomas. METHODS: Sixty patients (32 males, 28 females, mean age 69.3±11.3 years) were enrolled: 31 (51.7%) had IPMNs and 29 (48.3%) had histologically confirmed pancreatic adenocarcinomas. Thirty blood donors were also studied as controls. In all study subjects, the concentrations of VEGF, VEGF-D, VEGFR-2, and endostatin were determined using enzyme-linked immunosorbent assays. RESULTS: Serum concentrations of VEGF, VEGF-D, and VEGFR-2 were significantly higher in patients with pancreatic ductal adenocarcinoma and those with IPMNs compared with healthy subjects, while endostatin was significantly higher only in patients with pancreatic ductal adenocarcinoma compared with healthy subjects. Within the group of patients, VEGFR-2 was significantly higher in patients with ductal adenocarcinoma compared to those with IPMNs. The sensitivity and the specificity of VEGFR-2 in differentiating patients with ductal adenocarcinomas from those with IPMN at a cut-off range of 4003-4034 pg/mL was 86.2% and 54.8%, respectively. CONCLUSIONS: IPMNs have serum VEGFR-2 concentrations different from those in patients with ductal adenocarcinomas. However, serum VEGFR-2 cannot be routinely utilized to differentiate IPMNs from pancreatic ductal adenocarcinomas.

Is the pancreas affected in patients with septic shock?--a prospective study.

BACKGROUND: Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock. This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls. METHODS: The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock. All patients also underwent radiological examination to detect pancreatic abnormalities. RESULTS: The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period, while the serum activity of lipase was similar to that of the control subjects. Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock. None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis. CONCLUSION: The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage, and the management of these patients should be dependent on the clinical situation and not merely the biochemical results.

Distinguishing features between patients with acute diverticulitis and diverticular bleeding: Results from the REMAD registry.

BACKGROUND: Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications. AIMS: to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding. METHODS: Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding. RESULTS: Age was significantly lower (OR 0.48, 95% CI: 0.34-0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11-2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60-27.0) and diverticulitis (OR 4.23, 95% CI: 1.11-16.1). CONCLUSION: This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.

Serum leptin, but not adiponectin and receptor for advanced glycation end products, is able to distinguish autoimmune pancreatitis from both chronic pancreatitis and pancreatic neoplasms.

OBJECTIVE: Serum leptin and adiponectin determinations have been proposed as markers for distinguishing pancreatic cancer and chronic pancreatitis from autoimmune pancreatitis; however, no studies exist in patients with autoimmune pancreatitis and in those with intraductal papillary mucinous tumors of the pancreas. The aim of this paper was to evaluate the circulating concentrations of receptor for advanced glycation end products (RAGE), leptin and adiponectin in patients with chronic pancreatic diseases. MATERIAL AND METHODS: Seventy-five consecutive patients with chronic pancreatic diseases (47 males, 28 females; mean age 67.0 +/- 13.2 years; range 37-97 years) were studied: six (8.0%) had autoimmune pancreatitis, 23 (30.7%) had chronic pancreatitis, 34 (45.3%) had pancreatic cancer and the remaining 12 (16.0%) had intraductal papillary mutinous tumors of the pancreas. Leptin, adiponectin and RAGE were determined in serum using commercially available kits. The leptin concentrations were normalized to the lower and upper reference limits because of the different gender reference ranges. RESULTS: Normalized leptin concentrations were significantly lower in chronic pancreatitis patients (0.53 +/- 1.28; p = 0.008) and in those with pancreatic cancer (0.12 +/- 0.33; p < 0.001) compared to the overall population (0.58 +/- 1.23), whereas autoimmune pancreatitis patients had significantly higher concentrations of this protein (2.18 +/- 2.56; p = 0.004) compared to the overall population. RAGE and adiponectin concentrations were similar among the four groups of patients studied. Among the clinical variables considered, only pain was significantly related to leptin concentrations (patients with pain 0.18 +/- 0.54, patients without pain 1.07 +/- 1.64; p = 0.001). CONCLUSION: Serum leptin seems to be a good serum marker for differentiating autoimmune pancreatitis patients from those with chronic pancreatitis and pancreatic cancer.

Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms.

OBJECTIVES: Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal complaints in IBS patients remains poorly elucidated. METHODS: We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire. RESULTS: IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia. CONCLUSIONS: A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients.

Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta-analysis.

High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver-operating characteristic curve analysis was carried out by means of Meta-DiSc open-access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve [+/- SE]: 0.920 +/- 0.073, 0.914 +/- 0.191, and 0.949 +/- 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.

Exocrine pancreatic function during the early recovery phase of acute pancreatitis.

BACKGROUND: Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis, but the data are scarce and conflicting. This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding. METHODS: Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their first episode of the disease. They were 75 patients including 60 (80.0%) patients with mild acute pancreatitis and 15 (20.0%) patients with severe acute pancreatitis. Etiologically 61 patients (81.3%) had biliary disease, 1 (1.3%) had alcoholic disease and 3 (4.0%) had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients (13.3%). The mean (+/-SD) refeeding time after the attack of acute pancreatitis was 11.2+/-10.2 days. RESULTS: Pathological values of fecal elastase-1 were found in 9 of the 75 patients (12.0%): 7 (9.3%) patients with mild pancreatitis and 2 (2.7%) patients with severe pancreatitis (P=1.000). The frequency of the pathological values of fecal elastase-1 was significantly different from that of various etiologies of the disease (P=0.030). It was significantly lower in patients with biliary pancreatitis (9.8%; P=0.035) than in one patient with alcoholic pancreatitis (P=0.126), one patient with hypertriglyceridemia-induced pancreatitis (33.3%; P=0.708), and one patient with idiopathic pancreatitis (10.0%; P=0.227). Pathological fecal elastase-1 was not significantly related to sex, age or day of refeeding. CONCLUSION: Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.

New insights on diabetes in Turner syndrome: results from an observational study in adulthood.

OBJECTIVE: To explore the characteristics of diabetes mellitus in adults with Turner syndrome. DESIGN: Observational study consisting of a prospective phase after the access of adults with Turner syndrome to the Endocrinology Unit (median period of follow-up 15.6, interquartile range: 12.0-24.5 months) and a retrospective collection of data from the diagnosis of Turner syndrome until the time of access to the Endocrinology Unit. A total of 113 Italian Turner syndrome patients were included in the study. During the prospective phase of the study, each patient underwent physical examination, fasting blood sampling, and an oral glucose tolerance test on a yearly basis. Oral glucose tolerance test was used to perform the diagnosis of diabetes mellitus. RESULTS: Before access to the Endocrinology Unit, diabetes mellitus was diagnosed in two Turner syndrome patients. Another five cases of diabetes mellitus were diagnosed at the first access to the Endocrinology Unit, whereas seven new cases of diabetes mellitus were diagnosed during the prospective phase of the study. At the diagnosis of diabetes mellitus, only one patient had fasting glucose above 126 mg/dL, and only two had an HbA1c value >6.5% (48 mmol/mol). When compared to normo-glucose tolerant patients, the diabetic patients had a significantly lower insulin-to-glucose ratio at 30 and 60 min of the oral glucose tolerance test. In the regression analyses, only age was associated with the development of diabetes mellitus. CONCLUSIONS: This study confirms that diabetes mellitus is frequent in Turner syndrome and suggests that it is specific to the syndrome. In addition, this study demonstrates that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome.

Hydrogen sulfide, nitric oxide and a molecular mass 66 u substance in the exhaled breath of chronic pancreatitis patients.

BACKGROUND/AIMS: Human exhaled breath contains many molecules either present as gases or occurring in a soluble form in the vapor of the breath. This study was designed to evaluate the substances present in the exhaled breath of chronic pancreatitis (CP) patients. SUBJECTS: Thirty-one consecutive CP patients (11 with exocrine insufficiency) and 31 healthy subjects (HS) were studied. METHODS: Ninety-eight different substances were analyzed using a mass spectrometer on a breath sample from all subjects and on each respective ambient air sample. RESULTS: H(2)S, NO and a substance having a molecular mass of 66 u (M66) were those which had significantly higher concentrations in CP patients than in HS after adjustment for the ambient air; the estimated increases attributable to the disease were 14% (p = 0.040) for H(2)S, 84% (p = 0.006) for M66 and 50% (p = 0.033) for NO, but the three volatile compounds showed poor diagnostic accuracy in differentiating CP patients from HS (AUC-ROC: 0.664, 0.715, and 0.602 for H(2)S, M66, and NO, respectively). Finally, no significant differences of H(2)S, M66, and NO were found between patients with and without alcoholic pancreatitis as well as between patients with and without pancreatic insufficiency. CONCLUSIONS: Exhaled breath analysis can rapidly and easily assess the presence of volatile compounds (H(2)S, NO and a substance having a molecular mass of 66 u) which may have properties capable of explaining, at least in part, the pathogenesis of CP.

Fecal calprotectin and elastase 1 determinations in patients with pancreatic diseases: a possible link between pancreatic insufficiency and intestinal inflammation.

BACKGROUND: Fecal calprotectin determination has been demonstrated to be useful in diagnosing various inflammatory diseases of the gastrointestinal tract; however, data available for patients with pancreatic diseases are scarce. Our aim was to assess fecal calprotectin in order to evaluate the presence of intestinal inflammation in patients with pancreatic disease. METHODS: Eligible patients with suspected pancreatic illness were enrolled, and in all of them fecal calprotectin and elastase-1, as well as serum amylase and lipase activities, were assayed using commercially available kits. RESULTS: A total of 90 subjects (47 men, 43 women, mean age 58.6 +/- 14.9 years) were enrolled: 20 (22.2%) had chronic pancreatitis; 15 (16.7%) had pancreatic cancer; six (6.7%) had chronic nonpathological pancreatic hyperenzymemia; 16 (17.8%) had nonpancreatic diseases; and 23 (25.6%) had no detectable diseases. Diarrhea was present in 19 patients (21.1%). In univariate analyses, the presence of diarrhea and low fecal elastase-1 concentrations were significantly associated (P = 0.019 and P = 0.002, respectively) with abnormally high fecal calprotectin concentration, and the multivariate analysis demonstrated that low fecal elastase-1 concentration was the only variable independently associated with a high fecal calprotectin concentration. CONCLUSIONS: Pancreatic insufficiency may cause intestinal inflammation, probably because of a modification of the intestinal ecology.

Is Serum Total LDH Evaluation Able to Differentiate between Alimentary Lymphoma and Inflammatory Bowel Disease in a Real World Clinical Setting?

CONTEXT: An increase in enzyme lactate dehydrogenase (LDH) in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD) and alimentary lymphoma are common diseases in cats. OBJECTIVE: The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases. MATERIALS AND METHODS: A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured. RESULTS: Gender (P = 0.016) and age (P = 0.046) were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%), a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80%) of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively). CONCLUSIONS: Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population.

Attitudes of women of advanced maternal age undergoing invasive prenatal diagnosis and the impact of genetic counselling.

Despite the increasing availability and effectiveness of non-invasive screening for foetal aneuploidies, most women of advanced maternal age (AMA) still opt for invasive tests. A retrospective cross-sectional survey was performed on women of AMA undergoing prenatal invasive procedures, in order to explore their motivations and the outcome of preliminary genetic counselling according to the approach (individual or group) adopted. Of 687 eligible women, 221 (32.2%) participated: 117 had received individual counselling, while 104 had attended group sessions. The two groups did not differ by socio-demographic features. The commonest reported reason to undergo invasive tests was AMA itself (67.4%), while only 10.4% of women mentioned the opportunity of making informed choices. The majority perceived as clear and helpful the information received at counselling, and only 12.7% had doubts left that, however, often concerned non-pertinent issues. The impact of counselling on risk perception and decisions was limited: a minority stated their perceived risk of foetal abnormalities had either increased (6.8%) or reduced (3.6%), and only one eventually declined invasive test. The 52.6% of women expressed a preference toward individual counselling, which also had a stronger impact on perceived risk reduction (P=0.003). Nevertheless, group counselling had a more favourable impact on both clarity of understanding and helpfulness (P=0.0497 and P=0.035, respectively). The idea that AMA represents an absolute indication for invasive tests appears deeply rooted; promotion of non-invasive techniques may require extensive educational efforts targeted to both the general population and health professionals.

Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen.

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.

Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome.

BACKGROUND/OBJECTIVE: In order to follow the most recent developments and recommendations in trial methodology for drug evaluation in patients with irritable bowel syndrome, we performed an extended analysis of a large clinical trial from a previously published study of otilonium bromide, using an assessment that integrates the key symptoms of irritable bowel syndrome. MATERIALS AND METHODS: A large-scale clinical trial with a double-blind, placebo-controlled, parallel-group study design was conducted in 378 patients, treated for 15 weeks with the recommended standard dose of 40 mg otilonium bromide or placebo three times daily. The study was based on the collection of 12 single efficacy endpoints. The new efficacy assessment was based on the data reported by the patients. Rather than demonstrating score differences between the treatment groups of the study, we carried out an assessment that integrates the most frequent symptoms reported (pain frequency and intensity, presence of meteorism and distension) by the patient. RESULTS: The rate of response to treatment within 2-4 months (the primary efficacy outcome measure) was significantly higher in the otilonium bromide group (36.9%) than in the placebo group (22.5%; P = 0.007). In each month of treatment, the rate of monthly response was higher in the otilonium bromide group as compared to the placebo group (P < 0.05). The total monthly and weekly responses to the single endpoints (intensity and frequency of pain and discomfort, meteorism/abdominal distension, severity of diarrhoea or constipation and mucus in the stool) were significantly more frequent in the group treated with otilonium bromide than in the placebo-treated group, with differences ranging from 10% to 20%. The subgroup analysis of the intestinal habits endpoint indicates that patients with diarrhoea have an additional benefit. CONCLUSION: The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome, being very efficient in relieving pain and discomfort.

The availability of original data and statistics: an improvement in good publication practice.

The purpose of this paper is to highlight the aspects of good publication practices, with particular reference to data analysis, and to propose an innovative initiative for improving the quality of scientific information in this field. Several committees within the scientific community provide information and publish guidelines in order to support scientists in the application of good publication practices and to improve quality in medical research. Those guidelines suggest that the possibility of verifying the original data warrants the reliability of the published results by reducing the occurrence of misconduct related to data analysis. The initiative proposed in this article is aimed at making the original data and the statistical reports available to the scientific community together with the actual paper. Such a practice is undoubtedly an improvement in the quality of publication permitting verification of the results as well as allowing for further elaboration of the same data.

Pancreatic involvement in Salmonella infection.

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.

Different reconstruction techniques after pancreatoduodenectomy do not affect clinical and patient reported outcomes.

PURPOSE: To evaluate the quality of life in a 2-year follow-up study in consecutive subjects who underwent pancreaticoduodenectomy with different reconstruction techniques: pancreaticojejunostomy or pancreaticogastrostomy. PATIENTS/METHODS: One hundred and ninety-seven consecutive patients were studied: 164 (83.2%) had malignant and 33 (16.8%) had benign disease. The EORTC QLQ-C30 questionnaire was administered at 5 different time points for evaluation: before surgery, and 6, 12, 18 and 24 months after discharge. RESULTS: Pancreaticojejunostomy was performed in 189 patients (95.9%) and pancreaticogastrostomy in 8 patients (4.1%). In the follow-up evaluation, the quality of life significantly improved using the various surgical approaches; improvement over time was not significantly different among the various reconstruction techniques. CONCLUSIONS: In clinical practice, different surgical reconstruction techniques are equally effective in improving the quality of life after pancreaticoduodenectomy.