Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. METHODS: We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. RESULTS: Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p < 0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p < 0.01). CONCLUSION: The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.

Role of fecal calprotectin in gastrointestinal disorders.

BACKGROUND: Fecal calprotectin (FC) has been proposed as a useful and non-invasive marker of acute intestinal inflammation. AIM: We summarize recent evidences on FC, providing practical perspectives on its diagnostic and prognostic role in different gastrointestinal conditions. MATERIALS AND METHODS: We performed a MEDLINE search for all articles published on FC in human gastroenterology field up to December 2011. We chose evidences from well-designed and controlled studies when available. A meta-analysis was not performed because of the heterogeneity of these studies. RESULTS: Most of relevant data derived from studies on inflammatory bowel disease (IBD). FC concentrations (FCCs) showed a good diagnostic precision for separating organic and functional intestinal diseases and well correlated with IBD activity. FCCs were higher in subjects with NSAID enteropathy, but the actual correlation between FC and endoscopy is under investigation. FCCs can not be recommended for colorectal neoplasia population screening purpose. Few and heterogeneous studies have been performed in order to evaluate role of FC in other gastrointestinal conditions. CONCLUSIONS: FC has been widely proposed as a filter to avoid unnecessary endoscopies. Nevertheless, it should not be considered as a marker of organic intestinal disease at all; rather it represents a marker of "neutrophilic intestinal inflammation". In IBD, more and larger studies are needed to confirm FC's capacity to correlate with IBD extent, to predict response to therapy and relapse, and the presence of a subclinical intestinal inflammation in asymptomatic first-degree relatives of patients. For NSAID enteropathy, the actual correlation between FC and endoscopic results needs further confirmation. Finally, as regarding other gastrointestinal conditions, available data are still insufficient to draw any final conclusion and further studies should be encouraged.

Reduced performance of Troponin T for acute coronary syndromes diagnosis in the elderly and very elderly patients: a retrospective study of 2688 patients.

STUDY OBJECTIVE: We evaluated the performance of Troponin T (cTnT) for acute coronary syndrome (ACS) diagnosis in elder compared to younger patients. MATERIALS AND METHODS: We retrospectively evaluated 2688 patients admitted to our Emergency Department for suspected ACS. All patients received ECG, serum creatinine determination, and serial cTnT samplings. Patients were considered positive for cTnT if they had a cTnT above our reference standard (>0.03 microg/L) in any determination obtained within 6 hours from admission. ACS diagnosis, either acute myocardial infarction or unstable angina, was based on reviewed data and discharge diagnosis hospital. Patients were divided in three groups according to age: <65-years-old, elders > or =65 and <80 years, and very elders > or =80 years. CTnT diagnostic accuracy for ACS was compared in these three groups in patients <65 years. RESULTS: Two thousands six and hundred eighty-eight patients (35.3% female) were enrolled in this study. 1087 patients (40.4%) were <65 years old, while 1205 patients (44.8%) were >or =65 and <80 years, and 396 patients (14.8%) were > or =80 years. The overall sensitivity of cTnT for ACS diagnosis was 0.57 (CI 95% 0.54-0.60) with a specificity of 0.71 (CI 95% 0.69-0.73). In older cohorts cTnT showed a reduced performance for ACS diagnosis. Area under the receiver operating characteristic curve of abnormal cTnT for ACS was 0.70 (0.66-0.73) in <65 years, 0.61 (95% CI 0.60-0.66) in > or =65 and <80 years, and 0.59 (0.53-0.65) in > or =80 years. CONCLUSION: Compared to younger patients cTnT showed a reduced performance for ACS diagnosis in elders > or =65 and <80 years; cTnT performance was further reduced in patients > or =80 years.

[Comparison of a new medical device with domperidone in functional dyspepsia: a randomized, cross-over, controlled study]. / Confronto tra un nuovo dispositivo medico e domperidone in pazienti con dispepsia funzionale: studio randomizzato, cross-over, controllato.

AIM: Management of functional dyspepsia is still controversial. Different controlled trials reported a superiority of prokinetics, H2-receptor antagonists and proton-pump inhibitors over placebo; nevertheless, symptomatic improvement after therapy is often incomplete and some of these drugs possess serious side effects. The aim of the study was to evaluate the efficacy of a new medical device in respect to domperidone in patients with functional dyspepsia. METHODS: In a cross-over, randomized trial, 36 patients with functional dyspepsia ingested two daily doses of a medical device (Digerfast) or domperidone (Peridon) for 21 days. Clinical evaluation was performed at baseline (T0) and after 21 days (T1) for each treatment. A Visual Analogue Scale (VAS) and the generic scale 36-item Short Form (SF-36) were used to assess symptom intensity and changes in health-related quality of life, respectively. RESULTS: At T0 no statistical difference was found for each symptom between medical device and domperidone. At T1 both treatments significantly improved in respect to baseline values all the evaluated gastrointestinal symptoms (P<0.5 for all comparisons) except for vomiting. No difference in gastrointestinal symptoms between the two treatments was found at T1. Regarding SF-36 evaluation, at T0 no statistical differences were found for each SF-36 parameter between the two regimens. At T1 both treatments significantly improved most of the evaluated SF-36 parameters in respect to baseline values. No difference in SF-36 parameters between the two treatments was found at T1. CONCLUSION: Both the medical device and domperidone significantly improved gastrointestinal symptoms and quality of life in subjects with functional dyspepsia, not showing significant difference in efficacy.

Probiotic intake unmasking a gastro-pleural fistula.

OBJECTIVE: Gastropleural fistula represents a rare clinical event often resulting in an iatrogenic complication of gastrointestinal surgery. Clinical presentation is insidious, patients complain of chronic and non-specific respiratory symptoms and may be conservatively treated for lung infections for several months until detailed tests finally reveal the correct diagnosis. PATIENTS AND METHODS: We describe a case of a healthy patient with an unexpected diagnosis of empyema due to a gastropleural fistula. RESULTS: A 51-year-old man with a past history of splenectomy for cyst was admitted because of high fever and cough. A chest radiography and CT-scan revealed a left-side pneumonia complicated with pleural empyema. Broad spectrum empirical antibiotics and pleural drainage did not significantly improve the clinical picture. While the need for a surgical complex thoracic approach becomes a collective awareness, questions about causes of empyema and its unfavorable evolution in our patient did not initially find a common satisfactory answer. It was only by the identification of probiotics bacteria in the pleural fluid that a gastropleural fistula was suspected, and then, it was confirmed by CT-scan and by digestive endoscopy. A combined thoraco-abdominal surgical treatment was therefore scheduled, leading to progressive improvement till total healing. CONCLUSIONS: Although gastropleural fistula is rare, it is necessary to include this pathological condition in the differential diagnosis of a persistent complicated pneumonia, because early diagnosis and, consequently, surgical management, may significantly impact on the prognosis of these patients. In our case, the detection of probiotics bacteria in the pleural fluid helped us to suspect and to look for the fistula.

Severe giant cell arteritis associated with essential thrombocythaemia.

Giant-cell arteritis (GCA) is a chronic vasculitis of the elderly usually involving the ophthalmic arteries, which can result in visual loss. High platelet counts may have some pathogenic significance in the obstruction of the ophthalmic circulation and a few cases of associated essential thrombocythaemia and GCA have been described. Here we report a case of severe temporal arteritis associated with essential thrombocythaemia.

Evaluation of symptoms and palatability in healthy volunteers after ingestion of an iced dessert by using different flavours.

It is well-known that digestion has a pivotal role in maintaining a state of wellbeing. The influence of certain foods and some herbal drugs has been ascertained. Epidemiological data show that the Mediterranean diet, with a high consumption of fresh vegetables and fruit, mainly citrus, has a beneficial effect and plays a protective gastrointestinal role. Previously, we assessed the influence on the eventual occurrence of symptoms during digestion of an iced dessert containing a mixture of digestive plant extracts, citrus juices and liquors, showing that its ingestion does not cause significant gastrointestinal symptoms in healthy volunteers. Taking into consideration that sensory properties of food may also influence digestion, we also evaluated the palatability of the product. In order to evaluate the effect of different tastes on the digestive processes, we performed a further similar evaluation with two new flavours. The ingestion of these iced desserts at the end of the meal does not cause significant gastrointestinal symptoms. Moreover, palatability median score shows a good appreciation of the products. Therefore, the combination of digestive herbs, citrus juice and liquors in different flavours gives rise to a product with a positive mix of good palatability, favourable acceptance and herbal constituents, able to maintain a good digestive condition.

Clinical features of familial Mediterranean fever: an Italian overview.

Familial Mediterranean Fever (FMF) is the most frequent periodic febrile syndrome among the autoinflammatory syndromes (AS), nowadays considered as innate immunity disorders, characterized by absence of autoantibodies and autoreactive T lymphocytes. FMF is a hereditary autosomal recessive disorder, characterized by recurrent, self-limiting episodes of short duration (mean 24e72 h) of fever and serositis. In FMF, periodic attacks show inter- and intra-individual variability in terms of frequency and severity. Usually, they are triggered by apparently innocuous stimuli and may be preceded by a prodromal period. The Mediterranean FeVer gene (MEFV) responsible gene maps on chromosome 16 (16p13) encoding the Pyrine/Marenostrin protein. The precise pathologic mechanism is still to be definitively elucidated; however a new macromolecular complex, called inflammasome, seems to play a major role in the control of inflammation and it might be involved in the pathogenesis of FMF. The most severe long-term complication is type AA amyloidosis, causing chronic renal failure. Two types of risk factors, genetic and non-genetic, have been identified for this complication. Currently, the only effective treatment of FMF is the colchicine. New drugs in a few colchicine resistant patients are under evaluation

Evaluation of effects (symptoms and palatability) after ingestion of "Gran Soleil" in healthy volunteers.

A good digestion is essential to maintain a healthy status. It is known that physiological digestive processes could be improved by the ingestion of some medicinal plants, while specific foods can facilitate the occurrence of gastrointestinal symptoms. Moreover, sensory properties of food seem to also influence digestion. We assessed the influence on physiological digestive processes of two Gran Soleil (GS) products containing a mixture of digestive plant extracts, citrus juices and liquors. We evaluated, in 10 healthy volunteers, the eventual occurrence of gastrointestinal symptoms after their ingestion and measured their palatability. Ingestion of GS did not cause significant gastrointestinal symptoms. Moreover, the palatability median score shows a good appreciation of the products. In conclusion, it is possible to suppose that a product with a good palatability, able to support and maintain a good digestive condition, derives from the mixture of digestive herbs, citrus juices, liquor and other ingredients.

Sjogren's syndrome in a celiac patient: searching for environmental triggers.

In the last few years many studies have shown the potential role of different triggers in the pathogenesis of several autoimmune diseases. In particular, in Sjogren's syndrome the presence of a genetic background is considered determining, but environmental factors have recently been described as triggers or precipitators. In this report, we describe the case of a young woman affected by celiac disease in which an Ascaris lumbricoides infestation and estrogen therapy could have played a role in the development of Sjogren's syndrome.

Hypokalemic nephropathy in an adult patient with partial empty sella: a classic Bartter's syndrome, a Gitelman's syndrome or both?

Bartter's syndrome belongs to a group of hypokalemic renal channel diseases. These channels are located in the lipid layer of cell membranes where they exist as water channels through which ion transport is performed. Based on the type of genetic disorder and clinical presentation, Bartter's syndrome is classified as neonatal, classical and Gitelman's syndrome. Most of the cases have been noted in pediatric age groups and adult-onset cases are very rare. Moreover, an association between Bartter's syndrome and empty sella has recently been reported in 3 children. We report here the second case of an adult patient affected by Bartter's syndrome with partial empty sella. The patient showed some clinical and histological characteristics of both classic Bartter's syndrome and Gitelman's syndrome, suggesting that genotype and phenotype of Bartter's syndrome are not so clear-cut and that phenotypic overlap may occur, according to a recent hypothesis. Magnetic resonance imaging disclosed a partial empty sella. A thorough endocrinological investigation showed normal hypophyseal, thyroidal, adrenal and gonadal function. Good therapeutic effects were achieved using spironolactone, ACE-inhibitor and potassium supplementation, with normalization of the kalemia. At present, the value of the association of Bartter's syndrome and empty sella remains unclear and future studies are needed to clarify the importance of this association, both in children and in adult patients affected by Bartter's syndrome.

Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury.

BACKGROUND: Complement consists of a complex cascade of proteins involved in innate and adaptive immunity. The cascade can be activated through 3 distinct mechanisms, designated the classical, alternative, and lectin pathways. Although complement is widely accepted as participating in the pathophysiology of ischemia-reperfusion injury, the specific role of the lectin pathway has not been addressed. METHODS AND RESULTS: Monoclonal antibodies (mAbs; P7E4 and 14C3.74, IgG1kappa isotypes) were raised against rat mannose-binding lectin (rMBL). Both mAbs recognized rMBL-A by Western analysis or surface plasmon resonance. P7E4, but not 14C3.74, exhibited a concentration-dependent inhibition of the lectin pathway, with maximal effect at 10 microg/mL. In vivo, rats were subjected to 30 minutes of left coronary artery occlusion and 4 hours of reperfusion. Complement C3 deposition was greatly attenuated in hearts pretreated with P7E4 compared with 14C3.74-treated hearts. Pretreatment with P7E4 (1 mg/kg) significantly reduced myocardial creatine kinase loss (48%), infarct size (39%), and neutrophil infiltration (47%) compared with 14C3.74-treated animals. In addition, P7E4 pretreatment significantly attenuated the expression of proinflammatory genes (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) after ischemia-reperfusion. CONCLUSIONS: The lectin complement pathway is activated after myocardial ischemia-reperfusion and leads to tissue injury. Blockade of the lectin pathway with inhibitory mAbs protects the heart from ischemia-reperfusion by reducing neutrophil infiltration and attenuating proinflammatory gene expression.

Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

Normalisation of high CA 19-9 values in autoimmune hepatitis after steroidal treatment.

Carbohydrate 19-9 antigen (CA 19-9) is considered a specific marker of pancreatobiliary adenocarcinomas, but slight increase of its levels can be found in several non-malignant diseases of the liver, such as autoimmune hepatitis. We describe a case of marked CA 19-9 elevation (up to 898.0 U/ml) in a patient with autoimmune hepatitis. Laboratory and instrumental examinations excluded malignant diseases. Immunohistochemical analysis for CA 19-9 and MIB-1, performed on liver biopsy, showed reactivity in inflammatory areas, in particular in bile ductule cells and hepatocytes in ductular metaplasia, suggesting that these cells could be involved in CA 19-9 serum levels increase. After steroids, the clinical picture improved and all the laboratory parameters normalised.

Effect of exogenous beta-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of the addition to milk, 5 min and 10 h before its consumption, of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance. DESIGN: Double-blind, placebo-controlled, crossover study. SETTING: University Hospital. SUBJECTS: In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated. INTERVENTIONS: Each patient underwent three H(2) breath tests, in a random order. We used 400 ml of cow's semiskimmed milk as substrate and a beta-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the beta-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H(2) concentration, the cumulative H(2) excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea). RESULTS: Our study showed a significant reduction of the mean maximum H(2) concentration after both test A (12.07 +/- 7.8 p.p.m.) and test B (13.97 +/- 7.99 p.p.m.) compared with test C (51.46 +/- 16.12 p.p.m.) (ANOVA F = 54.33, P < 0.001). Similarly, there was a significant reduction of the mean cumulative H(2) excretion after both test A (1428 +/- 1156 p.p.m.) and test B (1761 +/- 966 p.p.m.) compared with test C (5795 +/- 2707 p.p.m.) (ANOVA F = 31.46, P < 0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36 +/- 0.55) and test B (0.96 +/- 0.85) compared with test C (3.7 +/- 0.79) (ANOVA F = 106.81, P < 0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferroni's P = 0.03). CONCLUSIONS: Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.

Anisakis infestation: a case of acute abdomen mimicking Crohn's disease and eosinophilic gastroenteritis.

Anisakiasis is a rare parasitic disease transmitted to humans by the ingestion of raw fish, which can initially present with acute abdomen. We report the case of a man, a habitual consumer of raw fish, who underwent surgery for acute abdomen, initially attributed to Crohn's disease and then later interpreted as eosinophilic enteritis. Only the subsequent careful histological examination of the surgical specimen, revealing full thickness eosinophilic infiltrate, generally typical of infestation, led to the detection of Anisakis simplex larva. In cases of acute abdomen, in the presence of a positive history of raw fish ingestion, it is therefore reasonable to consider the possibility of anisakiasis.

Hypercreatininemia and hyperglycemia: diabetic nephropathy or "inverted peritoneal auto-dialysis"?

We describe a case of 51-year-old male with fever, abdominal pain and inguino-scrotal hernia. Laboratory examination revealed hypercreatininemia and hyperglycemia, firstly interpreted as diabetic nephropathy. US and CT scan showed a hernia of the bladder into the scrotum. Surgery revealed multiple bladder perforations with peritoneal diffusion of urine. So, hypercreatininemia was caused by peritoneal reabsorption of urea and creatinine, a condition that may be described as "inverted peritoneal auto-dialysis". Surgical reposition and repairment of the bladder led to rapid normalization of serum urea and creatinine. Discharged diagnosis was intraperitoneal rupture of inguino-scrotal hernia of the bladder in patient with recent onset of diabetes mellitus.

Nutrient intakes of formula-fed infants and infants fed cow's milk.

Twenty-four-hour dietary intake data from the second National Health and Nutrition Examination Survey (NHANES II), 1976-1980, were analyzed to compare nutrient intakes among infants 7 to 12 months of age who were fed mixed diets containing solid foods and either infant formula or cow's milk. Solid foods fed to the infants in both groups were low in iron and linoleic acid, and high in sodium, potassium, and protein, relative to Recommended Dietary Allowances. Infants who were fed cow's milk received lower median intakes of iron (7.8 mg v 14.9 mg), linoleic acid (1.8 g v 6.1 g), and vitamin C (39 mg v 64 mg), and higher median intakes of protein (41 g v 25 g), sodium (1,000 mg v 580 mg), and potassium (1,630 mg v 1,020 mg) than formula-fed infants. Seventy-five percent of the infants fed cow's milk had iron intakes below the Recommended Dietary Allowance; 69% had sodium intakes above the range of estimated safe and adequate daily dietary intake. Linoleic acid provided less than 3% of energy intake for 74% of the infants fed cow's milk. Differences in nutrient intakes were due not only to different concentrations of nutrients in each of the milk feedings but also to the different amounts and types of solid foods fed to the two groups of infants.

Helicobacter pylori eradication using one-week low-dose lansoprazole plus amoxycillin and either clarithromycin or azithromycin.

AIM: To evaluate and compare two 1-week low-dose triple therapies based on lansoprazole, amoxycillin and a macrolide in eradicating Helicobacter pylori. METHODS: Seventy consecutive patients, suffering from dyspeptic symptoms with H. pylori infection, were randomly allocated to one of two treatment groups: (A) (LAC; n = 35) lansoprazole 30 mg once daily, amoxycillin 1000 mg b.d., clarithromycin 250 mg b.d., all for 7 days; and (B) (LAA; n = 35) lansoprazole 30 mg once daily and amoxycillin 1000 mg b.d., both for 7 days, plus azithromycin 500 mg once daily for only 3 days. The H. pylori status was evaluated by means of histology and rapid urease test at entry and 8 weeks after treatment. RESULTS: Three patients did not complete the treatment: one in the LAC group was withdrawn owing to severe side-effects; two patients in the LAA group stopped the treatment prematurely. H. pylori eradication was obtained in 28 of 34 (82%; 95% CI = 66-93%) patients in the LAC group and in 20 of 33 (61%; 95% CI = 42-77%) patients in the LAA group. The difference is significant (P < 0.029). On intention-to-treat analysis, the rates of eradication were (28 of 35 patients, 80% in the LAC group and 20 of 35 patients, 57% in the LAA group. Side-effects occurred in nine (26%) and six (18%) patients in the LAC and LAA groups, respectively. CONCLUSIONS: Low-dose lansoprazole plus amoxycillin and clarithromycin is more effective than low-dose lansoprazole plus amoxycillin and azithromycin, but it gave a greater incidence of side-effects.