Association between familial mediterranean fever and retroperitoneal fibrosis: retroperitoneal fibrosis regression after colchicine therapy.

Retroperitoneal fibrosis (RPF) is a disease characterized by inflammatory fibrotic processes affecting the retroperitoneal structures. Familial Mediterranean Fever (FMF) is an autosomal recessive disorder, characterized by fever and attacks of sterile serositis. Colchicine is the only suitable drug for prevention of acute episodes. We describe a case of association between RPF and FMF in a 48-year-old male, in whom therapy with colchicine, besides preventing acute episodes, allowed RPF regression. To date the association between FMF and RPF and the use of colchicine therapy alone for RPF has not been described.

Abnormal synthesis of IgA in coeliac disease and related disorders.

The pathogenesis of coeliac disease (CD) is complex. One controversial aspect is the role of IgA anti-endomysial (EMA) antibodies. Despite being the most reliable marker for CD diagnosis, its role in the pathogenesis (if any) remains obscure. The paradox is reinforced by the observation that CD is more common in IgA-deficient individuals. In this review, we discuss recent data suggesting that IgA autoantibodies may be related to aspecific dysregulation of IgA. In addition, new insights have elucidated new genes involved in IgA production and linked to CD. Allelic frequency of HS1,2 enhancer which regulates Ig synthesis is altered in CD and other IgA mediated disorders. We suggest that in CD, a T-cell mediated disease, the role of IgA anti-EMA autoantibodies remains elusive and could well be merely an epiphenomenon not directly related to pathogenic mechanisms, but rather to a state of heightened immunological responsiveness in genetically predisposed individuals.

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn's disease with anal endosonographic monitoring: a single-centre experience.

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.

Diagnostic and therapeutic impact of double-balloon enteroscopy (DBE) in a series of 100 patients with suspected small bowel diseases.

BACKGROUND: Double-balloon enteroscopy is a newly developed endoscopic method allowing non-surgical full-length exploration of the small bowel, biopsies sample and endoscopic treatment of previously inaccessible lesions. AIM: To prospectively assess the diagnostic and therapeutical impact of double-balloon enteroscopy in patients with suspected or documented small bowel disease. PATIENTS AND METHODS: One hundred consecutive patients referring to our centre for suspected small bowel disease underwent double-balloon enteroscopy. Starting insertion route (anal or oral) of double-balloon enteroscopy was chosen according to the estimated location of the suspected lesions basing on the clinical presentation and on the findings, when available, of previous endoscopic or radiological investigations. Major indications for the procedures were acute recurrent or chronic mid-gastrointestinal bleeding (n=71), suspected gastrointestinal tumours (n=10), suspected Crohn's disease (n=6), chronic abdominal pain and/or chronic diarrhoea (n=8), refractory celiac disease (n=5). RESULTS: One hundred and eighteen double-balloon enteroscopy procedures were carried out. Oral and anal route double-balloon enteroscopies were performed in 54 and 28 patients, respectively, while 18 patients underwent a combination of both approaches. Overall diagnostic yield of double-balloon enteroscopy resulted 69%. Most common pathological findings included angiodysplasias (n=39), ulcerations and erosions of various aetiologies (n=21), tumours (n=7) and ileal stenosis in patients with Crohn's disease suspicion (n=2). In the 65% of the patients examined, double-balloon enteroscopy findings influenced the subsequent clinical management (endoscopic, medical or surgical treatment). No major complications related to the procedure occurred. CONCLUSIONS: Our prospective analysis shows that double-balloon enteroscopy is a useful, safe and well-tolerated new method with a high diagnostic and therapeutic impact for the management of suspected or documented small bowel diseases.

How to use the C-reactive protein in cardiac disease?

Inflammation is an important contributor to atherothrombosis. The C-reactive protein (CRP) is not only an excellent biomarker of inflammation, but it is also a direct participant in atherogenesis. CRP consistently predicts new coronary events, including myocardial infarction and death, in patients with ischemic heart disease. The predictive value of CRP is, in the majority of the studies, independent of and additive to that of the troponins and its levels can be modulated by statins. Prospective observational studies show that moderately elevated levels of CRP are associated with an adverse cardiovascular prognosis among healthy individuals. The availability of high sensibility assays for CRP should provide a valuable tool for identifying patients at risk of cardiovascular events in primary prevention in conjunction with lowering LDL cholesterol and may also have utility in the treatment of acute coronary syndromes with percutaneous coronary intervention (PCI) therapy. High CRP levels, associated with a higher risk, should suggest a more aggressive medical therapy in the long term and also an aggressive and invasive therapy in the short term, including the use of GP IIb/IIIa inhibitors, high doses of statins, and when a PCI is necessary, provisional stenting. Finally, CRP will provide a readily accessible marker for further testing of the inflammatory hypothesis in atherosclerosis.

Increased levels of NF-kappaB inhibitors (IkappaBalpha and IkappaBgamma) in the intestinal mucosa of Crohn's disease patients during infliximab treatment.

The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease.

BACKGROUND: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed. METHODS: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). RESULTS: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01). CONCLUSIONS: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.

Three-day antibiotic therapy with azithromycin and tinidazole plus lansoprazole or pantoprazole to cure Helicobacter pylori infection: a pilot study.

OBJECTIVE: The aim of the present study was to investigate and compare the effects of two proton-pump inhibitors, lansoprazole (Limpidex 30 mg, Sigmatau) vs pantoprazole (Peptazol 40 mg, Boehringer Mannheim), included in a three-day antibiotic therapy regimen with azithromycin (Zitromax 500 mg, Pfizer) and tinidazole (Fasigin 500 mg, Pfizer). DESIGN: Seventy consecutive, H. pylori-positive patients were randomly pre-treated with lansoprazole 30 mg o.d. (once daily) or pantoprazole 40 mg o.d. for two days, and subsequently respectively assigned to one of the two following treatment regimens, given for only three days: regimen A (LAT) comprising lansoprazole 30 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. (bis in die), or regimen B (PAT) comprising pantoprazole 40 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. H. pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C-urea breath test alone 8 weeks after treatment. MAIN OUTCOME MEASURES: Sixty-nine of the enrolled patients completed the study: 34 in the LAT group and 35 in the PAT group. One patient in the LAT group was lost to follow-up. In the LAT group, after the end of treatment, 28/34 patients were H. pylori-negative (per protocol: 82%; intention-to-treat: 80%). In the PAT group, after treatment, 29/35 patients were H. pylori-negative (per protocol and intention-to-treat: 83%). Mild or slight side-effects occurred in only one patient in the LAT group and in one in the PAT group. CONCLUSIONS: From this study there is no evidence that either of the two proton-pump inhibitors used is preferable in a three-day antibiotic regimen with azithromycin and tinidazole. The excellent side-effect and tolerability profiles, associated with acceptable eradication rates, make the two treatment regimens we tested particularly useful when patient compliance is difficult to achieve.

Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes.

BACKGROUND: Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted. OBJECTIVE: To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. METHODS: We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects). RESULTS: In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P < .001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P < .001, EF = 0.74), and lower frequency of DR4 (3/24 = 12% ns). CONCLUSIONS: These data suggest that the immune mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.

MLH1 and MSH2 constitutional mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer.

Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) may have a significant impact on the clinical management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for the selection of candidates for genetic testing. However, reports of mismatch repair (MMR) gene mutations in families not fulfilling the minimal diagnostic criteria point out the necessity to identify additional clinical parameters suggestive of genetic predisposition to colorectal cancer (CRC) related to MMR defects. We thus investigated a series of 32 Italian putative HNPCC individuals selected on the basis of one of the following criteria: 1) family history of CRC and/or other extracolonic tumors; 2) early-onset CRC; and 3) presence of multiple primary malignancies in the same individual. These patients were investigated for the presence of MLH1 and MSH2 mutations by single-strand conformation polymorphism analysis. Pathogenetic truncating mutations were identified in 4 (12.5%) cases, 3 of them involving MSH2 and 1 MLH1. In addition, 2 missense MLH1 variants of uncertain significance were observed. All pathogenetic mutations were associated with early age (<40 years) at onset and proximal CRC location. Our results support the contention that constitutional MMR mutations can also occur in individuals without the classical HNPCC pattern. Moreover, evaluation of the clinical parameters associated with MMR mutations indicates that early onset combined with CRC location in the proximal colon can be definitely considered suggestive of MMR-related hereditary CRC and should be included among the guidelines for referring patients for genetic testing.

Food allergy in children: results of a standardized protocol for oral desensitization.

BACKGROUND/AIMS: Food allergy in children is still an unresolved problem that merits investigation, particularly when the food is fundamental for the child's growth. Reports in the literature that deal with the possibility of a desensitizing treatment are sporadic and often inconsistent, and no standardized protocols are yet available. In this paper we propose a standardized oral desensitization program for food allergy in children. METHODOLOGY: The treatment was carried out in 14 cases with allergy to food (milk in 6 cases, egg in 5, fish in 2 and apple in 1 case). The control group consisted of 10 age and sex matched allergic subjects (5 to milk, 4 to egg and 1 to fish), who underwent a strict elimination diet regimen. RESULTS: Compliance to treatment was satisfactory, since 12 out of the 14 treated cases (85.7%) completed the program. Treatment was successful in 100% of the cases that completed the program: all the treated patients are now able to tolerate any food with no untoward effects or need for preventive drugs. CONCLUSIONS: The proposed standardized oral desensitization treatment may represent a safe and convenient alternative in the management of food-allergic subjects.

Leucocytoclastic vasculitis associated with hepatitis C virus antibodies.

The actiopathogenesis of leucocytoclastic vasculitis is still unknown, but recently hepatitis C virus (HCV) has been suggested as trigger of autoimmunity. We report a case of a 26-yr-old patient with purpura due to leucocytoclastic vasculitis associated with hepatitis C virus infection. Laboratory findings showed AST, ALT, gamma GT within normal limits, positive antibodies to HCV (IIF and Riba II) and polymerase chain reaction for HCV RNA. Anti-nuclear antibodies, IgG and IgM anti-cardiolipin antibodies, anti-platelet antibodies and anti-neutrophil cytoplasmic antibodies with perinuclear pattern were also present. A skin biopsy specimen of a purpuric lesion showed leucocytoclastic vasculitis with small vessel thrombosis and perivascular deposition of IgM and fibrinogen on immunofluorescence study. This case shows a role of HCV in leucocytoclastic vasculitis; it is possible that this HCV can induce autoimmunity independently of cryoglobulins and liver involvement.

Chronic pancreatitis prevalence in liver cirrhosis. Morphological and functional study.

Ductal pancreatic changes and functional exocrine assessment have been studied, in a group of 60 cirrhotic patients. In these patients the aetiology of cirrhosis was alcoholism in 35, hepatitis B virus-hepatitis C virus infection in 19, primary biliary cirrhosis in 2 and not determinable in 4. Eighteen patients (30%) showed an endoscopic retrograde pancreatography picture consistent with chronic pancreatitis (14 mild, 2 moderate and 2 severe). Mild pancreatographic changes were present in 7 alcoholic (20%) and in 7 non-alcoholic cirrhosis patients (28%). Moderate and severe abnormalities were present only in alcoholic cirrhosis (4 patients, 11.4%). No correlation was found between presence or pancreatopathy degree and Child-Pugh score or cirrhosis duration. Functional exocrine tests were abnormal only in severe endoscopic retrograde pancreatography picture. Mild type ductal lesions can mimic either age-dependent changes or chronic pancreatitis. The absence of impaired functional tests makes it impossible to discriminate between these two possibilities. These findings emphasize that in our cirrhotic group the prevalence of chronic pancreatitis (with a moderate or severe endoscopic retrograde pancreatography picture) is low (6.6%) and alcoholism is always present. Possibly, cirrhosis with secretion of high-volume low protein concentration juice confers a protective effect on the pancreas.

[Therapeutic action of S-adenosylmethionine in some chronic hepatopathies]. / Attività terapeutiche della solfo-adenosilmetionina in alcune epatopatie croniche

Albuminopoyesis, prothrombin activity, BSF clearance, bioptic and sometimes also laparoscopic pictures have been examined in order to test the hepatic activity of SAMe. This study has been carried out in patients suffering from liver cirrhosis and other chronic hepatites. The above-mentioned parameters proved to be significantly improved in almost all the 25 patients studied and checked after 30 and 60 days' treatment with 30-45 mg SAMe administered by slow intravenous route.