Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Clinical identification and long-term surveillance of 22 hereditary non-polyposis colon cancer Italian families.

OBJECTIVE: To assess the efficacy of a hereditary non-polyposis colon cancer (HNPCC) identification and surveillance policy. METHODS: Familial clustering of colorectal cancer (CRC) and extracolonic cancers (ECs) was investigated in 1520 consecutive CRC patients and relatives. HNPCC was identified by Amsterdam criteria, and individuals at risk were offered biennial colonoscopy and other examinations, starting from age 25 years. RESULTS: Twenty-two HNPCC families were identified. The CRC prevalence was 27.8% (121/435), decreasing from 59.4% in the first generation to 24.4% and 8% in the second and third generation, respectively. Twenty-nine patients had multiple CRC and 34 patients (in 12 families) had ECs.A total of 199/331 at-risk individuals accepted surveillance. The mean follow-up was 48+/-32 months. CRCs were detected at first surveillance in four out of 199 surveilled individuals (2%); in two surveilled individuals (1%), three CRCs developed during follow-up. The overall CRC incidence was 7/199 (3.5%) in surveilled individuals and 5/132 (3.7%) in unsurveilled individuals. CRCs were less advanced in surveilled than in unsurveilled patients. Eleven individuals had 22 adenomas (one with high-grade dysplasia). Three individuals had adenomas at first surveillance; two of them and eight more individuals during surveillance. Seven surveilled individuals and six unsurveilled individuals, all belonging to families with a history of EC, had EC during the study period. All patients with CRC detected by surveillance are alive. One of the unsurveilled patients who had CRC died 18 months after the diagnosis. CONCLUSIONS: Data confirm the importance of the family history collected in each patient with CRC for identification of HNPCC and support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at-risk members. Reasons for surveillance failure could be an accelerated progression of small adenomas and a lesion missing at colonoscopy. Longer follow-up is required to assess the efficacy of surveillance for EC.

Hepatitis B and C virus infection in Crohn's disease.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.

Rectosigmoid polyps as markers of proximal colonic neoplasms: a cost benefit analysis of different diagnostic protocols.

The predictive value of hyperplastic polyps of the rectosigmoid for neoplastic lesions in the proximal colon is controversial. Some authors who deny predictive value have proposed a protocol which entails initially biopsying rectosigmoid polyps, and only in the case of adenomas then proceeding to total colonoscopy (protocol 1). The diagnostic and economic efficiency of this protocol, and of an alternative which entailed the full exploration of the colon during the initial examination in the case of rectosigmoid polyps (protocol 2), were evaluated by retrospectively simulating their application to 216 patients who had undergone total colonoscopy. A proximal neoplastic pathology was present in 49.5% of patients with rectosigmoid adenoma, 27.3% of patients with distal non neoplastic polyps alone (33.3% if only distal hyperplastic polyps were considered) and 11% of patients with no distal polyps. Protocol 1 gave rise to a higher cost ($ 58,413), not only compared to protocol 2 ($ 50,276), but also compared to total colonoscopy in all patients ($ 57,008); there was also a larger number of patients who eluded diagnosis (29%, against 16% in protocol 2). In terms of cost per lesion detected and of colorectal cancers prevented (on the basis of an evolution to cancer of 5% of adenomas), total colonoscopy for all patients on principle is advantageous compared to either protocol ($ 864 per proximal lesion and $ 7,082 per cancer prevented). Since distal hyperplastic polyps are also predictive of proximal neoplastic pathology, when rectosigmoid polyps are detected it is both indicated and economic to proceed with the exploration of the entire colon during the initial examination. This appears to be a reasonable compromise compared to total colonoscopy on principle, which has higher overall costs. The latter management, however, should not be ruled out, since it has a better diagnostic yield and lower cost per lesion detected and per cancer prevented.

Pattern analysis of serum alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma in liver cirrhosis.

In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.

Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patient's symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are traditionally considered to be at high risk for duodenal-papillary and periampullary adenomas and cancer. AIM: To evaluate prospectively the prevalence, histology and clinical significance of ampullary and periampullary macroscopic and microscopic lesions in our population of affected patients. SETTING: Three gastroenterological departments of northern Italian hospitals. PATIENT AND METHODS: Twenty-five affected patients were carefully investigated over a 24-month period by end-viewing and side-viewing upper panendoscopy. Biopsies were performed on representative macroscopic lesions and randomly on normal-appearing papillary and periampullary mucosa. RESULTS: Seven patients had macroscopic adenomas of the duodenal papilla, three of the periampullary region and five at both sites (cumulative prevalence 40%). An additional six patients had macroadenomas in the rest of the duodenum (overall prevalence 64%). Microscopic adenomas were identified in nine and two patients in the papilla and periampullary region, respectively, and in three at both sites (overall prevalence 44%). Thus, a total of 17 (68%) patients presented macro- or microadenomas at these locations. The prevalence rose to 72%, when a further patient with macroadenomas in the rest of the duodenum only was included. Malignancy was not encountered and severe dysplasia was observed only in a macroadenoma of the second duodenal portion. A higher frequency of macroadenomas in the papilla and periampullary region was significantly correlated with the presence and number of such lesions in the rest of the duodenum (P = 0.04). No other significant association was detected either between micro- or macroadenomas at different sites or with the demographic, clinical and pathological features. CONCLUSION: This study confirms that the duodenal papilla and periampullary region are sites with high prevalence of macro- and microscopic adenomas in patients with FAP. However, our data do not seem to support a higher frequency and malignancy potential of such lesions as compared to polyps in the rest of the duodenum. Nevertheless, these findings warrant a periodic, careful examination of the duodenum with either end-viewing or side-viewing endoscopy, the need for random biopsies of the papilla and periampullary region and the removal of any larger or rapidly growing lesions detected.

Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.

OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated. METHODS: Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months. RESULTS: According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.

Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas.

Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 182 patients with single or multiple colorectal adenomas, and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09-18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q.

Outcome of laparoscopic colorectal resection.

BACKGROUND: The aim of this study was to assess the feasibility and safety of laparoscopic surgery for colorectal diseases. METHODS: A retrospective review was undertaken of all patients undergoing a laparoscopic colorectal procedure (LCP) for large bowel disease. All operations were performed by a single experienced team. Patients were divided chronologically into three consecutive groups (G1, G2, and G3). Data collection included the incidence and cause of both "proper" and "mandatory" conversions to laparotomy, the incidence and type of early and late postoperative complications, incidence of operative mortality, and the length of hospital stay. The incidences of conversion to laparotomy and of early and late postoperative complications were also determined as related to diagnosis, type of LCP attempted, and chronological group. RESULTS: Between January 1996 and December 2001, a total of 108 patients (49 men and 59 women) with a mean age of 65.1 years underwent an LCP for colorectal disease. Proper conversion to open surgery was necessary in five patients (4.6%), whereas a mandatory conversion was needed in 10 with patients advanced cancer (9.2%). The overall morbidity rate was 11.9%. There were no anastomotic leaks. In two patients (1.85%) developed a complication requiring reoperation. Postoperative mortality was nil. Mean postoperative hospital stay was 7.2 days. The rates of conversion and of early and late complications decreased through the three chronological periods. No trocar site recurrences were observed in the cancer patients. CONCLUSION: Laparoscopic colorectal surgery performed in experienced centers is safe; the observed morbidity and mortality rates are low and acceptable and compare favorably to those observed after standard open surgery.

Treatment and follow-up of large bowel adenoma.

The current clinical interest in large bowel adenoma is due to the evidence that most carcinomas arise in benign adenomas and therefore endoscopic removal of adenomas interrupts the sequence that leads to cancer. Colonoscopy is the best method for the detection and treatment of adenomas, with a diagnostic accuracy of 94% and a low incidence of complications. The majority of polyps can be resected by snare polypectomy. Regarding small polyps, snare polypectomy without current application is recommendable and hot biopsy should be avoided owing to a non negligible risk of hemorrage. Though clinical significance of small polyps is controversial, in our experience and in other studies they have a potential for malignant progression (2.4% of adenomas containing invasive carcinoma are 6 mm or less in diameter) and those located in the rectosigmoid are predictive of proximal neoplasms. If endoscopic polypectomy significantly reduces the incidence of colorectal cancer, patients submitted to adenoma removal have an increased risk for metachronous adenomas. Surveillance is therefore mandatory, once the presence of synchronous adenomas has been ruled out (clean colon). Risk factors for adenoma recurrence are family history, age, size of adenoma, multiple adenomas, dysplasia, villous histotype. Holding in due consideration compliance, risk of complications, logistic problems and costs, the following guide-lines can be proposed: total colonoscopy at the time of endoscopic polypectomy (to obtain a "clean colon") and, in the case of unsatisfactory examination, within one year. first check at 3 years and, if negative, subsequent check at 5 years. for small tubular adenomas surveillance is indicated only in the case they are multiple. The evaluation of some intermediate bio-markers might contribute to the predictive determination of adenoma recurrence, with the goal to select groups of patients with the highest risk of recurrence of adenomas.

Clinical aspects and management of hereditary non-polyposis colorectal cancer (HNPCC).

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomical dominant trasmitted disease phenotypically defined according to the "Amsterdam criteria" as follows: at least 3 affected relatives, one of whom first degree relative of other two, at least two successive generations affected. Important cardinal features are: 1) prevalent proximal location of cancers (above splenic flexure); 2) multiple synchronous or methachronous large bowel cancers; 3) early age of onset (<50 years); 4) presence of extracolonic cancers (endometrium, stomach, urinary tract, skin). The treatment is essentially surgical and total colectomy with ileo-rectum anastomosis is already proposed as standard procedure with annual endoscopic examination of retained rectum. The screening of individuals at risk, so determined by the analysis of pedigree or the results of molecular tests, must be performed every 1-2 years by colonoscopy starting around the age of 25 years. In this review are described and analysed the spectrum of the disease with particular attention to the frequency and characteristics of extracolonic cancers. Moreover, the guidelines of the surveillance and screening are reported following the data of the literature and as proposed by the International Collaborative Group (ICG-HNPCC).

[Prevalence of peptic ulcer in patients with various hepatopathies]. / Prevalenza della malattia peptica in pazienti con differenti epatopatie.

Aim of this study was to re-evaluate the overall prevalence of a peptic disease in 350 patients with liver diseases of different etiology and severity. A normal endoscopic picture was found in 82% of cases. Peptic lesions were found in 18% of total cases and were located in the duodenal (10.9%) and gastric (7.1%) wall. On the basis of the 15-20% rate, which most Authors think to be a reasonable estimate of the overall ulcer prevalence in normal population, the prevalence rate in this survey would suggest that there is no association between ulcer and liver disease. Ulcers were more commonly present in cirrhotic than in noncirrhotic patients. Both alcohol intake and cigarette smoking were identified as two ulcerogenic events in these patients while portal hypertension and etiology of liver disease were irrelevant factors. The contemporary occurrence of the three ulcerogenic factors (cirrhosis, smoking, and alcohol intake) in a given patient seems to potentiate each others as ulcerogenic event. It is concluded that patients with liver diseases share the same risk of developing a peptic disease as the general population.

[Early gastric cancer. Survival and prognostic factors in 95 consecutive cases]. / Early gastric cancer. Sopravvivenza e fattori prognostici in 95 casi consecutivi.

In order to characterize prognostic factors and therapeutic strategies for EGC, we have studied 95 patients operated on from 1980 to 1988. EGC was limited to the mucosa in 36% and extended to the submucosa in 64% of the cases. Lymph nodes involvement was observed in 13 patients; in 12 of them EGC extended to the submucosa. Gastric resection was performed in 73 and total gastrectomy in 22 patients with a postoperative mortality of 6% and 16% respectively. During the follow-up 8 patients died for causes related to EGC, 8 for unrelated causes. The 5 years survival rate was 79, without differences according to site, type, size and histology of EGC, lymph nodes involvement, type of gastrectomy; only EGC limited to the mucosa was associated with a better survival experience (96% vs 70% of tumors extended to the submucosa p less than 0.05). The prognosis of EGC is good and a curative surgery may be accomplished, especially if the lesion is limited to the mucosa. In EGC extended to the submucosa an accurate lymphadenectomy may further improve the prognosis, while total gastrectomy--de principe--carries a higher postoperative mortality, without significant improvement of the long term prognosis.

[Eosinophilic gastroenteritis and ascites. Clinical case]. / Gastroenterite eosinofila ed ascite. Caso clinico.

We report the case of a patient with recurrent subocclusive episodes and diarrhea (no malabsorption) associated with ascites, in the absence or liver, kidney or heart disease. The demonstration of hypereosinophilia in the peripheral blood and in the ascites fluid and the failure to identify parasitic or haematological disorders have led to a through examination of the stomach (Endoscopy, Echoendoscopy), small bowel (X-rays and Computerized Axial Tomography) and colon (colonoscopy) in a search for parietal lesions. The absence of segmental lesions and the observation of CAT images of diffuse, regular thickening of the ileum and of the mesentery, coupled with the monotonous clinical history spanning over three decades, have led to a diagnosis of eosinophilic gastroenteritis with involvement of the serosal layer. Serosal involvement is rare in eosinophilic disease of the gut; in analogy with other cases reported in the literature, steroids have improved clinical symptoms and normalized the hematological picture.

Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation.

The extracellular matrix polysaccharide hyaluronan (HA) exerts size-dependent effects on leukocyte behavior. Low-molecular weight HA is abundant at sites of active tissue catabolism and promotes inflammation via effects on Toll-like receptor signaling. Conversely, high-molecular weight HA is prevalent in uninjured tissues and is anti-inflammatory. We propose that the ability of high-molecular weight but not low-molecular weight HA to cross-link CD44 functions as a novel form of pattern recognition that recognizes intact tissues and communicates "tissue integrity signals" that promote resolution of local immune responses.

Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development.

The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75(NTR). Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain.