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.

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.

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.

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

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study.

BACKGROUND AND STUDY AIM: Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. PATIENTS AND METHODS: The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. RESULTS: At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. CONCLUSIONS: This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.

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.

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.

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.

Association of myasthenia gravis and antisynthetase syndrome: a case report.

Myasthenia gravis is a chronic disease of neuromuscular transmission caused by loss of acetylcholine receptors. It can be found in association with other autoimmune disorders. We report the case of a 47-yr-old woman affected by Myasthenia gravis who complained of fever, progressive weakness of proximal limb muscle, arthritis and Raynauds phenomenon and dyspnea. Chest X-rays and CT scan showed an interstitial lung disease; laboratory data indicated an inflammatory picture and increased serum muscle enzymes. Evaluation for infectious, metabolic, iatrogenic and neoplastic aetiologies was unrevealing. The patients clinical condition together with positive results on antisynthetase antibody assay lead to the diagnosis of antisynthetase syndrome. To our knowledge, this is the first report on the association of Myasthenia gravis with antisynthetase syndrome.

Atypical mole syndrome and congenital giant naevus in a patient with celiac disease.

We describe a case of a 28-year-old woman affected by celiac disease (CD) associated with rare multiple disorders of the cutaneous pigmentary system: atypical mole syndrome and congenital giant naevus. Some other rare skin lesions have been reported in association with celiac disease such as cutaneous sarcoidosic granuloma, bullous pemphigoid, ichthyosis, alopecia areata, erythema elevatum diutinum, sclero-atrophic lichen and primary cutaneous amyloidosis. This is the 1(st) report concerning celiac disease and congenital disorders of the pigmentary system.

Inhibition of complement C5 reduces local and remote organ injury after intestinal ischemia/reperfusion in the rat.

BACKGROUND & AIMS: Complement activation plays an important role in the local pathogenesis of ischemia/reperfusion (I/R) injury. We investigated the action of anti-C5 monoclonal antibody (mAb) on local and remote organ injuries after intestinal I/R in the rat. METHODS: Under anesthesia, functional anti-rat C5 mAb (18A), an isotype-matched control anti-C5 mAb (16C), or vehicle (phosphate-buffered saline) was administered 60 minutes before the superior mesenteric artery was occluded for 90 minutes and reperfused for 60 minutes. Tissue injury was assessed by lactate dehydrogenase release, myeloperoxidase activity, and microvessel relaxation. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, and intercellular adhesion molecule (ICAM)-1 expression was assessed by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: The loss of endothelium-dependent relaxation of microvessels from the superior mesenteric artery after I/R was significantly attenuated by 18A but not by 16C. Intestinal lactate dehydrogenase release after I/R was significantly reversed by 18A treatment. Anti-C5 treatment significantly inhibited the increased myeloperoxidase activity in the lung and intestine after intestinal I/R. Furthermore, increased intestinal TNF-alpha, IL-1alpha, and vascular ICAM-1 expression after I/R were significantly inhibited by anti-C5 mAb. CONCLUSIONS: Anti-C5 therapy significantly improved intestinal I/R tissue injury as well as lung injury.

Link between Helicobacter pylori infection and iron-deficiency anaemia in patients with coeliac disease.

BACKGROUND: Iron-deficiency anaemia is a frequent finding in coeliac disease. Recent investigations have identified Helicobacter pylori infection as a factor responsible for iron deficiency. We investigated the potential relationship between H. pylori and iron-deficiency anaemia in patients with coeliac disease. METHODS: We conducted a prospective observational cohort study on coeliac patients evaluated for iron-deficiency anaemia. An upper gastrointestinal endoscopy was performed and biopsy specimens of duodenal and gastric mucosa were taken for histological examination and assessment of Helicobacter pylori status. RESULTS: The initial database was 386 subjects. Of these, 24 were excluded because of concomitant potential causes of iron deficiency. Of the 362 enrolled patients, H. pylori was detected in 77 (21%) subjects; of these 55 (71%) had iron-deficiency anaemia. Among the 285 H. pylori-negative subjects, 81 (28%) showed anaemia (P < 0.001). We did not find significant differences in gastric histological aspects between patients with or without iron deficiency anaemia. CONCLUSIONS: This study shows a significant association between H. pylori infection and iron-deficiency anaemia in patients with coeliac disease. The discovery of iron-deficiency anaemia in coeliac subjects may constitute another indication for the diagnosis and treatment of this worldwide infection.

Isolation, characterization, and cloning of porcine complement component C7.

Activation of the complement system through the classical, alternative, or lectin pathway results in the formation of the terminal complement complex. C7 plays an integral role in the assembly of this complex with target cell membranes. To date, only human C7 has been cloned and characterized; thus, in this study, we characterized the porcine complement component C7. Porcine C7 was isolated by affinity chromatography as a single glycoprotein with an approximate molecular mass of 90 kDa and 100 kDa under reducing and nonreducing conditions, respectively. The full-length porcine C7 cDNA was isolated, and the predicted amino acid sequence exhibited 80% identity with human C7 with conservation of the cysteine backbone and two putative N-linked glycosylation sites. Porcine C7 mRNA expression was detected in all tissues investigated, except polymorphonuclear and mononuclear leukocytes. Addition of purified porcine C7 restored the hemolytic activity of C7-depleted human sera in a dose-dependent manner. A functionally inhibitory mAb against porcine C7 attenuated the hemolytic activity of human, rabbit, or rat sera, suggesting an important conserved C7 epitope among species. These data demonstrate that porcine and human C7 are highly conserved, sharing structural and functional characteristics.

Telomerase activation in human fibroblasts during escape from crisis.

The immortalization of human diploid fibroblasts requires the circumvention of both the senescence (M1) and crisis (M2) mechanisms of growth control. Cells expressing the SV40 T antigen virtually always bypass senescence, but only rarely escape crisis. The low frequency of this latter event indicates that cellular mutations are necessary to escape crisis. Thirteen subpopulations of T antigen-expressing human fibroblasts were cultured into crisis. Colonies that appeared to resume growth were assayed for telomerase activity, telomere maintenance, and the immortal phenotype. Our results show that 33 of 35 colonies were telomerase negative and were not immortal. Two colonies were telomerase positive when assayed in the first approximately 15 population doublings after crisis. The first was strongly positive, maintained telomeres at a stable short length, and was later determined to be immortal. The second initially had a weak telomerase signal, grew extremely slowly, and when examined had greatly elongated telomeres consistent with the ALT (alternative lengthening of telomeres) mechanism of telomere maintenance. These cells eventually grew faster and were later determined to be immortal. Additionally, two subpopulations had initially weak and later strong telomerase activity and the cells never entered a defined crisis period. We observed a perfect correlation between telomere maintenance and escape from crisis, supporting the hypothesis that the lack of stable telomeres causes crisis and that the ability to maintain telomeres abrogates crisis.

Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids.

Necrotizing enterocolitis (NEC) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone. Various combinations of inadequate tissue oxygenation, bacterial overgrowth, and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis. Presently, there is not a way to predict the onset of the disease or to prevent its occurrence. As part of risk-benefit assessment, we compared disease in hospitalized preterm infants fed a commercial (control) preterm formula or an experimental formula with egg phospholipids for a randomized, double-masked, clinical study of diet and infant neurodevelopment. Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula (2.9 versus 17.6%, p < 0.05), but had similar rates of bronchopulmonary dysplasia (23.4 versus 23.5%), septicemia (26 versus 31%), and retinopathy of prematurity (38 versus 40%). Compared with the control formula, the experimental formula provided 7-fold more esterified choline, arachidonic acid (AA, 0.4% of total fatty acids), and docosahexaenoic acid (0.13%). Phospholipids are constituents of mucosal membranes and intestinal surfactant, and their components, AA and choline, are substrates for intestinal vasodilatory and cytoprotective eicosanoids (AA) and the vasodilatory neurotransmitter, acetylcholine (choline), respectively. One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study. Regardless of the potential mechanism, a larger randomized trial designed to test the effect of this egg phospholipid-containing formula on NEC seems warranted.

Histologic types and surveillance of gastric polyps: a seven year clinico-pathological study.

BACKGROUND/AIMS: This is a seven-year prospective study based on all gastroscopic examinations of our patient population in order to study gastric polyps. METHODOLOGY: One hundred and twenty-one polyps, removed from 96 patients were analysed. All polyps, after endoscopic polypectomy, were classified according to their histotype. The follow-up was carried out in 49 patients for a mean time of 40 months. RESULTS: Polypoid lesions were more frequent in females (57.3%) and they were preferentially located in antrum (60.3%). Hyperplastic and inflammatory polyps were 55.4% and 28.9%, respectively, while adenomatous lesions were 9.9%. Four fundic gland polyps, 1 carcinoid, 1 type I early gastric cancer and 1 pancreatic heterotopia were also found. During the follow-up no malignant lesion was encountered. On the other hand 25 benign polyps were found in 19 patients. CONCLUSIONS: Our experience confirms that there is a close relationship between the size of the polyps and the neoplastic change. In fact, in our series all polyps were smaller than 2 cm and only one malignancy was found (an early gastric cancer). None of adenomatous polyps was associated with gastric adenocarcinoma. Our data also indicates that when a polypectomy is carried out for small polyps (smaller than 2 cm.) a strict follow-up is necessary for the neoplastic polyps only.

[Intestinal permeability]. / La permeabilità intestinale.

Intestinal mucosa has an absorptive function and acts also as a selective barrier against potential antigenic, toxic and carcinogenic substances. Intestinal permeability can be defined as the capacity of mucosal surface to be penetrate by specific substances through unmediated diffusion. There are two theories about molecular permeation routes: the first one hypothesizes a transcellular (through small pores), a paracellular (through big channels) and a lipophilic pathways; the second one gives a key role only to paracellular tight-junctions. In many diseases we can find changes in intestinal permeability evaluable by simple and non invasive tests, administering "per os" probe molecules. These substances cross the epithelium in different way and amount according to their physicochemical features and mucosal integrity; then they reach circulation and are eliminated in urines where they can be detected. The most frequently molecules used are mono/disaccharides, 51Cr-labelled ethylenediaminetetraacetate (51Cr-EDTA) and polyethylene glycol (PEG). This simple method has become more and more used for diagnostic and speculative aims. These intestinal permeability tests have a low specificity so they cannot be used for a definitive diagnosis of intestinal disease; nevertheless, the high sensitivity for intestinal mucosal damage could make them a necessary method to evaluate mucosal integrity after therapy, to select patients with a specific symptoms and to support, particularly in pediatric populations, more specific and invasive diagnostic tests.

Telomerase activation during the linear evolution of human fibroblasts to tumorigenicity in nude mice.

The ribonucleoprotein enzyme telomerase is active in most immortal cell lines, most tumors and all tumor-derived cell lines. The enzyme is important because it prevents continual shortening of telomeres and therefore plays a significant role in chromosome maintenance. In man, telomerase is not active in most somal cells with finite lifespans. Using the SV40 T antigen we immortalized and transformed to fully tumorigenic a human fibroblast cell strain. We wished to determine when telomerase was activated during this progression to tumorigenicity. Using the PCR-based TRAP assay we found that eight of eight immortal cell lines that were either not tumorigenic or rarely formed tumors were telomerase positive at the time of inoculation. Additionally, 10 of 11 newly immortal cell lines contained telomerase activity within the first 25-33 population doublings after crisis. None of the precrisis cells from which these immortal cells were derived were positive for telomerase activity. Thus we found that telomerase activation is not the final in vivo step in the transformation of these cells and the window of activation is usually near the escape from crisis or M2. These results strengthen the hypothesis that telomerase activation may allow the rare cell to escape from crisis in those immortal cell populations dependent on telomerase for telomere maintenance.