Illuminating type collections of nectriaceous fungi in Saccardo's fungarium.

Specimens of Nectria spp. and Nectriella rufofusca were obtained from the fungarium of Pier Andrea Saccardo, and investigated via a morphological and molecular approach based on MiSeq technology. ITS1 and ITS2 sequences were successfully obtained from 24 specimens identified as 'Nectria' sensu Saccardo (including 20 types) and from the type specimen of Nectriella rufofusca. For Nectria ambigua, N. radians and N. tjibodensis only the ITS1 sequence was recovered. On the basis of morphological and molecular analyses new nomenclatural combinations for Nectria albofimbriata, N. ambigua, N. ambigua var. pallens, N. granuligera, N. peziza subsp. reyesiana, N. radians, N. squamuligera, N. tjibodensis and new synonymies for N. congesta, N. flageoletiana, N. phyllostachydis, N. sordescens and N. tjibodensis var. crebrior are proposed. Furthermore, the current classification is confirmed for Nectria coronata, N. cyanostoma, N. dolichospora, N. illudens, N. leucotricha, N. mantuana, N. raripila and Nectriella rufofusca. This is the first time that these more than 100-yr-old specimens are subjected to molecular analysis, thereby providing important new DNA sequence data authentic for these names.

Fungal Planet description sheets: 716-784.

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetopsina eucalypti on Eucalyptus leaf litter, Colletotrichum cobbittiense from Cordyline stricta × C. australis hybrid, Cyanodermella banksiae on Banksia ericifolia subsp. macrantha, Discosia macrozamiae on Macrozamia miquelii, Elsinoë banksiigena on Banksia marginata, Elsinoë elaeocarpi on Elaeocarpus sp., Elsinoë leucopogonis on Leucopogon sp., Helminthosporium livistonae on Livistona australis, Idriellomyces eucalypti (incl. Idriellomyces gen. nov.) on Eucalyptus obliqua, Lareunionomyces eucalypti on Eucalyptus sp., Myrotheciomyces corymbiae (incl. Myrotheciomyces gen. nov., Myrotheciomycetaceae fam. nov.), Neolauriomyces eucalypti (incl. Neolauriomyces gen. nov., Neolauriomycetaceae fam. nov.) on Eucalyptus sp., Nullicamyces eucalypti (incl. Nullicamyces gen. nov.) on Eucalyptus leaf litter, Oidiodendron eucalypti on Eucalyptus maidenii, Paracladophialophora cyperacearum (incl. Paracladophialophoraceae fam. nov.) and Periconia cyperacearum on leaves of Cyperaceae, Porodiplodia livistonae (incl. Porodiplodia gen. nov., Porodiplodiaceae fam. nov.) on Livistona australis, Sporidesmium melaleucae (incl. Sporidesmiales ord. nov.) on Melaleuca sp., Teratosphaeria sieberi on Eucalyptus sieberi, Thecaphora australiensis in capsules of a variant of Oxalis exilis. Brazil, Aspergillus serratalhadensis from soil, Diaporthe pseudoinconspicua from Poincianella pyramidalis, Fomitiporella pertenuis on dead wood, Geastrum magnosporum on soil, Marquesius aquaticus (incl. Marquesius gen. nov.) from submerged decaying twig and leaves of unidentified plant, Mastigosporella pigmentata from leaves of Qualea parviflorae, Mucor souzae from soil, Mycocalia aquaphila on decaying wood from tidal detritus, Preussia citrullina as endophyte from leaves of Citrullus lanatus, Queiroziella brasiliensis (incl. Queiroziella gen. nov.) as epiphytic yeast on leaves of Portea leptantha, Quixadomyces cearensis (incl. Quixadomyces gen. nov.) on decaying bark, Xylophallus clavatus on rotten wood. Canada, Didymella cari on Carum carvi and Coriandrum sativum. Chile, Araucasphaeria foliorum (incl. Araucasphaeria gen. nov.) on Araucaria araucana, Aspergillus tumidus from soil, Lomentospora valparaisensis from soil. Colombia, Corynespora pseudocassiicola on Byrsonima sp., Eucalyptostroma eucalyptorum on Eucalyptus pellita, Neometulocladosporiella eucalypti (incl. Neometulocladosporiella gen. nov.) on Eucalyptus grandis × urophylla, Tracylla eucalypti (incl. Tracyllaceae fam. nov., Tracyllalales ord. nov.) on Eucalyptus urophylla. Cyprus, Gyromitra anthracobia (incl. Gyromitra subg. Pseudoverpa) on burned soil. Czech Republic, Lecanicillium restrictum from the surface of the wooden barrel, Lecanicillium testudineum from scales of Trachemys scripta elegans. Ecuador, Entoloma yanacolor and Saproamanita quitensis on soil. France, Lentithecium carbonneanum from submerged decorticated Populus branch. Hungary, Pleuromyces hungaricus (incl. Pleuromyces gen. nov.) from a large Fagus sylvatica log. Iran, Zymoseptoria crescenta on Aegilops triuncialis. Malaysia, Ochroconis musicola on Musa sp. Mexico, Cladosporium michoacanense from soil. New Zealand , Acrodontium metrosideri on Metrosideros excelsa, Polynema podocarpi on Podocarpus totara, Pseudoarthrographis phlogis (incl. Pseudoarthrographis gen. nov.) on Phlox subulata. Nigeria, Coprinopsis afrocinerea on soil. Pakistan, Russula mansehraensis on soil under Pinus roxburghii. Russia, Baorangia alexandri on soil in deciduous forests with Quercus mongolica. South Africa, Didymocyrtis brachylaenae on Brachylaena discolor. Spain, Alfaria dactylis from fruit of Phoenix dactylifera, Dothiora infuscans from a blackened wall, Exophiala nidicola from the nest of an unidentified bird, Matsushimaea monilioides from soil, Terfezia morenoi on soil. United Arab Emirates, Tirmania honrubiae on soil. USA, Arxotrichum wyomingense (incl. Arxotrichum gen. nov.) from soil, Hongkongmyces snookiorum from submerged detritus from a fresh water fen, Leratiomyces tesquorum from soil, Talaromyces tabacinus on leaves of Nicotiana tabacum. Vietnam, Afroboletus vietnamensis on soil in an evergreen tropical forest, Colletotrichum condaoense from Ipomoea pes-caprae. Morphological and culture characteristics along with DNA barcodes are provided.

Phylloporus and Phylloboletellus are no longer alone: Phylloporopsis gen. nov. (Boletaceae), a new smooth-spored lamellate genus to accommodate the American species Phylloporus boletinoides.

The monotypic genus Phylloporopsis is described as new to science based on Phylloporus boletinoides. This species occurs widely in eastern North America and Central America. It is reported for the first time from a neotropical montane pine woodland in the Dominican Republic. The confirmation of this newly recognised monophyletic genus is supported and molecularly confirmed by phylogenetic inference based on multiple loci (ITS, 28S, TEF1-α, and RPB1). A detailed morphological description of P. boletinoides from the Dominican Republic and Florida (USA) is provided along with colour images of fresh basidiomata in habitat, line drawings of the main anatomical features, transmitted light microscopic images of anatomical features and scanning electron microscope images of basidiospores. The taxonomic placement, ecological requirements and distribution patterns of P. boletinoides are reviewed and the relationships with phylogenetically related or morphologically similar lamellate and boletoid taxa such as Phylloporus, Phylloboletellus, Phyllobolites and Bothia are discussed.

Fungal Planet description sheets: 558-624.

Novel species of fungi described in this study include those from various countries as follows: Australia: Banksiophoma australiensis (incl. Banksiophoma gen. nov.) on Banksia coccinea, Davidiellomycesaustraliensis (incl. Davidiellomyces gen. nov.) on Cyperaceae, Didymocyrtis banksiae on Banksia sessilis var. cygnorum, Disculoides calophyllae on Corymbia calophylla, Harknessia banksiae on Banksia sessilis, Harknessia banksiae-repens on Banksia repens, Harknessia banksiigena on Banksia sessilis var. cygnorum, Harknessia communis on Podocarpus sp., Harknessia platyphyllae on Eucalyptus platyphylla, Myrtacremonium eucalypti (incl. Myrtacremonium gen. nov.) on Eucalyptus globulus, Myrtapenidiella balenae on Eucalyptus sp., Myrtapenidiella eucalyptigena on Eucalyptus sp., Myrtapenidiella pleurocarpae on Eucalyptuspleurocarpa, Paraconiothyrium hakeae on Hakea sp., Paraphaeosphaeria xanthorrhoeae on Xanthorrhoea sp., Parateratosphaeria stirlingiae on Stirlingia sp., Perthomyces podocarpi (incl. Perthomyces gen. nov.) on Podocarpus sp., Readeriella ellipsoidea on Eucalyptus sp., Rosellinia australiensis on Banksia grandis, Tiarosporella corymbiae on Corymbia calophylla, Verrucoconiothyriumeucalyptigenum on Eucalyptus sp., Zasmidium commune on Xanthorrhoea sp., and Zasmidium podocarpi on Podocarpus sp. Brazil: Cyathus aurantogriseocarpus on decaying wood, Perenniporia brasiliensis on decayed wood, Perenniporia paraguyanensis on decayed wood, and Pseudocercospora leandrae-fragilis on Leandrafragilis.Chile: Phialocephala cladophialophoroides on human toe nail. Costa Rica: Psathyrella striatoannulata from soil. Czech Republic: Myotisia cremea (incl. Myotisia gen. nov.) on bat droppings. Ecuador: Humidicutis dictiocephala from soil, Hygrocybe macrosiparia from soil, Hygrocybe sangayensis from soil, and Polycephalomyces onorei on stem of Etlingera sp. France: Westerdykella centenaria from soil. Hungary: Tuber magentipunctatum from soil. India: Ganoderma mizoramense on decaying wood, Hodophilus indicus from soil, Keratinophyton turgidum in soil, and Russula arunii on Pterigota alata.Italy: Rhodocybe matesina from soil. Malaysia: Apoharknessia eucalyptorum, Harknessia malayensis, Harknessia pellitae, and Peyronellaea eucalypti on Eucalyptus pellita, Lectera capsici on Capsicum annuum, and Wallrothiella gmelinae on Gmelina arborea.Morocco: Neocordana musigena on Musa sp. New Zealand: Candida rongomai-pounamu on agaric mushroom surface, Candida vespimorsuum on cup fungus surface, Cylindrocladiella vitis on Vitis vinifera, Foliocryphia eucalyptorum on Eucalyptus sp., Ramularia vacciniicola on Vaccinium sp., and Rhodotorula ngohengohe on bird feather surface. Poland: Tolypocladium fumosum on a caterpillar case of unidentified Lepidoptera.Russia: Pholiotina longistipitata among moss. Spain: Coprinopsis pseudomarcescibilis from soil, Eremiomyces innocentii from soil, Gyroporus pseudocyanescens in humus, Inocybe parvicystis in humus, and Penicillium parvofructum from soil. Unknown origin: Paraphoma rhaphiolepidis on Rhaphiolepsis indica.USA: Acidiella americana from wall of a cooling tower, Neodactylaria obpyriformis (incl. Neodactylaria gen. nov.) from human bronchoalveolar lavage, and Saksenaea loutrophoriformis from human eye. Vietnam: Phytophthora mekongensis from Citrus grandis, and Phytophthora prodigiosa from Citrus grandis. Morphological and culture characteristics along with DNA barcodes are provided.

Fungal Planet description sheets: 320-370.

Novel species of fungi described in the present study include the following from Malaysia: Castanediella eucalypti from Eucalyptus pellita, Codinaea acacia from Acacia mangium, Emarcea eucalyptigena from Eucalyptus brassiana, Myrtapenidiella eucalyptorum from Eucalyptus pellita, Pilidiella eucalyptigena from Eucalyptus brassiana and Strelitziana malaysiana from Acacia mangium. Furthermore, Stachybotrys sansevieriicola is described from Sansevieria ehrenbergii (Tanzania), Phacidium grevilleae from Grevillea robusta (Uganda), Graphium jumulu from Adansonia gregorii and Ophiostoma eucalyptigena from Eucalyptus marginata (Australia), Pleurophoma ossicola from bone and Plectosphaerella populi from Populus nigra (Germany), Colletotrichum neosansevieriae from Sansevieria trifasciata, Elsinoë othonnae from Othonna quinquedentata and Zeloasperisporium cliviae (Zeloasperisporiaceae fam. nov.) from Clivia sp. (South Africa), Neodevriesia pakbiae, Phaeophleospora hymenocallidis and Phaeophleospora hymenocallidicola on leaves of a fern (Thailand), Melanconium elaeidicola from Elaeis guineensis (Indonesia), Hormonema viticola from Vitis vinifera (Canary Islands), Chlorophyllum pseudoglobossum from a grassland (India), Triadelphia disseminata from an immunocompromised patient (Saudi Arabia), Colletotrichum abscissum from Citrus (Brazil), Polyschema sclerotigenum and Phialemonium limoniforme from human patients (USA), Cadophora vitícola from Vitis vinifera (Spain), Entoloma flavovelutinum and Bolbitius aurantiorugosus from soil (Vietnam), Rhizopogon granuloflavus from soil (Cape Verde Islands), Tulasnella eremophila from Euphorbia officinarum subsp. echinus (Morocco), Verrucostoma martinicensis from Danaea elliptica (French West Indies), Metschnikowia colchici from Colchicum autumnale (Bulgaria), Thelebolus microcarpus from soil (Argentina) and Ceratocystis adelpha from Theobroma cacao (Ecuador). Myrmecridium iridis (Myrmecridiales ord. nov., Myrmecridiaceae fam. nov.) is also described from Iris sp. (The Netherlands). Novel genera include (Ascomycetes): Budhanggurabania from Cynodon dactylon (Australia), Soloacrosporiella, Xenocamarosporium, Neostrelitziana and Castanediella from Acacia mangium and Sabahriopsis from Eucalyptus brassiana (Malaysia), Readerielliopsis from basidiomata of Fuscoporia wahlbergii (French Guyana), Neoplatysporoides from Aloe ferox (Tanzania), Wojnowiciella, Chrysofolia and Neoeriomycopsis from Eucalyptus (Colombia), Neophaeomoniella from Eucalyptus globulus (USA), Pseudophaeomoniella from Olea europaea (Italy), Paraphaeomoniella from Encephalartos altensteinii, Aequabiliella, Celerioriella and Minutiella from Prunus (South Africa). Tephrocybella (Basidiomycetes) represents a novel genus from wood (Italy). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Minced umbilical cord fragments as a source of cells for orthopaedic tissue engineering: an in vitro study.

A promising approach for musculoskeletal repair and regeneration is mesenchymal-stem-cell- (MSC-)based tissue engineering. The aim of the study was to apply a simple protocol based on mincing the umbilical cord (UC), without removing any blood vessels or using any enzymatic digestion, to rapidly obtain an adequate number of multipotent UC-MSCs. We obtained, at passage 1 (P1), a mean value of 4, 2 × 10(6) cells (SD 0,4) from each UC. At immunophenotypic characterization, cells were positive for CD73, CD90, CD105, CD44, CD29, and HLA-I and negative for CD34 and HLA-class II, with a subpopulation negative for both HLA-I and HLA-II. Newborn origin and multilineage potential toward bone, fat, cartilage, and muscle was demonstrated. Telomere length was similar to that of bone-marrow (BM) MSCs from young donors. The results suggest that simply collecting UC-MSCs at P1 from minced umbilical cord fragments allows to achieve a valuable population of cells suitable for orthopaedic tissue engineering.

Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease.

BACKGROUND: Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described. AIM: To explore potential interactions between thiopurines and concomitant medications. METHODS: A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments. RESULTS: Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7-29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016). CONCLUSIONS: Our data suggest the absence of significant interactions between thiopurines and 5-ASA.

The role of endoscopic assessment in ulcerative colitis in the era of infliximab.

Endoscopic evaluation of mucosal appearance is important for the clinical management of ulcerative colitis patients, as it offers valuable prognostic tools and data useful to change the management and treatment strategies. In the field of severe ulcerative colitis, partial endoscopy and bioptic sampling allows to obtain additional and relevant prognostic information: if severe endoscopic lesions are present, response to standard treatment is less likely, and if CMV superinfection is detected, anti-viral treatment should be added to conventional treatments. When clinical remission is obtained with conventional treatments, distal colonoscopy may add valuable data: the occurrence of complete endoscopic healing is a major predictor of long-term remission with no clinical activity. Finally, biologic treatments, and mainly infliximab, were shown to induce remarkable and significant mucosal healing also in ulcerative colitis, and patients with complete endoscopic healing in response to infliximab were shown to be more likely to experience fewer clinical relapses during the follow-up. Therefore endoscopic evaluation has to be considered a major prognostic marker in ulcerative colitis. In this review data from the Literature supporting this role will be reviewed.

Reproducibility of bowel ultrasonography in the evaluation of Crohn's disease.

BACKGROUND: Bowel ultrasonography is increasingly used in the detection and follow-up of patients with Crohn's disease, but a limitation to its further diffusion is the lack of standardisation of ultrasonography parameters. AIMS: This study aimed to standardise the most common bowel ultrasonography parameters in order to develop an unequivocal imaging interpretation and to assess bowel ultrasonography reproducibility. PATIENTS: Twenty patients with Crohn's disease were examined. METHODS: Six ultrasonographers (mean bowel ultrasonography experience=16 years) performed the study. They chose and discussed a common assessment methodology concerning eight ultrasonography parameters: bowel wall thickness, bowel wall pattern, bowel wall blood flow, enlarged mesenteric lymph nodes, mesenteric hypertrophy, abdominal free fluid, and stenosis or fistulae at four preliminary meetings. The day of the study operators were randomised to two rooms where they independently and in turn performed ultrasonography scans. Interobserver agreement was scored by kappa statistics. RESULTS: Excellent k values were observed for bowel wall thickness (0.72-1). k Values were poor for bowel wall pattern (-0.22-0.85) and good for bowel wall blood flow (0.53-0.89). The presence of lymph nodes was reproducible (0.56-0.90) except in one case (0.25). Concordance on free fluid was excellent (0.85-1), whereas that on mesenteric hypertrophy was generally poor (0.14-0.69). Agreement was excellent for stenosis (0.81-1) whereas that for fistula was fair in room abscesses (0.31-0.48) and very good in room B (0.87-1). CONCLUSION: Bowel ultrasonography signs used in Crohn's disease can be standardised as most of them showed a fair to good reproducibility. In particular, bowel wall thickness, the most relevant parameter for Crohn's disease detection, showed an excellent reproducibility.

Endoscopic ultrasound-fine needle aspiration (EUS-FNA) for pancreatic lesions: effectiveness in clinical practice.

BACKGROUND: Diagnosis of pancreatic masses is often difficult. Endoscopic ultrasound-fine needle aspiration has been proposed as the best single-step strategy. AIMS: To prospectively evaluate feasibility, effectiveness and safety of endoscopic ultrasound-fine needle aspiration of pancreatic masses in a consecutive study of unselected patients. METHODS: Two hundred ninety-three patients were enrolled in two referral Hospitals in Northern Italy. All patients were referred either due to the presence of imaging test abnormalities (suspected or evident masses, or features indirectly suggesting the presence of a mass) or due to clinical or biochemical findings suggesting pancreatic cancer in the absence of positive imaging. All patients underwent linear array endoscopic ultrasound and, when indicated, fine needle aspiration. All procedures were recorded prospectively. The final diagnosis was established at the end of follow-up or when the patients underwent surgery or died. RESULTS: Fine needle aspiration was indicated in 246 of 293 cases (84%), considered technically feasible in 232 of 246 cases (94%) and gave adequate samples for histopathological diagnosis in 204 of 232 cases (88%). Endoscopic ultrasound sensitivity, specificity and accuracy were 79, 60 and 72%, respectively; the corresponding figures for endoscopic ultrasound-fine needle aspiration were 80, 86 and 82%. There was good agreement with final diagnosis for endoscopic ultrasound-fine needle aspiration (kappa 0.673, 95%CI 0.592-0.753), greater than that for endoscopic ultrasound alone (kappa 0.515, 95%CI 0.425-0.605). There was one case of intracystic haemorrhage and one case of transient hyperthermia (0.3%). CONCLUSIONS: Endoscopic ultrasound-fine needle aspiration of pancreatic masses seems to be feasible, effective and safe in this consecutive study of patients.

Therapeutic ERCP in paediatric patients.

BACKGROUND: Major limitations of endoscopic retrograde cholangiopancreatography in paediatric populations are a low incidence of biliopancreatic disease among children, the equipment dimensions (size of endoscopes and devices) and the increasing role of MR-cholangiopancreatography in the field of diagnostic indications. Aim of this study was to evaluate the diagnostic and therapeutic yields of endoscopic retrograde cholangiopancreatography for biliopancreatic diseases in a paediatric population. METHODS: Between 1996 and 2002, 48 endoscopic retrograde cholangiopancreatographies were performed in 38 children aged 4 weeks to 17 years as part of the diagnostic evaluation for suspected pancreatic or biliary tract disease. Endoscopic retrograde cholangiopancreatography was carried out under general anaesthesia, using prototype paediatric duodenoscopes or standard duodenoscopes in children younger or older than 18 months, respectively. RESULTS: The indications to perform endoscopic retrograde cholangiopancreatography were common bile duct stones (14 children), biliopancreatic abnormalities (8), primary sclerosing cholangitis (2), Wirsung disruption (1), biliary leakage (1), cholestasis (4) and pancreatitis (8). Cannulation was successful in all patients but one. Sphincterotomy together with stone extraction or stent insertion was performed in 30/38 patients. Immediate complications were mild and treated conservatively. CONCLUSIONS: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography can be used safely and effectively in the management of biliopancreatic diseases in childhood as well. Indications, endoscopic techniques and complications are similar to those reported for adult patients.

Outcome of a conservative approach in severe ulcerative colitis.

BACKGROUND: Severe ulcerative colitis is potentially life threatening even though a policy of intensive medical management and early colectomy in recent years reduced mortality to almost zero. However, colectomy, with or without ileal-anal anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no reliable prognostic index of surgical outcome has been developed. Intravenous steroids are still the mainstay of medical therapy but their maximal duration before stating a 'treatment failure' has not been defined. AIM OF THE STUDY: To evaluate the effectiveness, safety and outcome of an intensive medical approach in a series of patients with severe ulcerative colitis. PATIENTS AND METHODS: One hundred and forty-nine episodes of severe ulcerative colitis in 115 patients admitted to a Gastroenterology Unit in a 7-year period were retrospectively evaluated. Intravenous glucocorticosteroids--methylprednisolone 1 mg/kg/day--and topical steroids were administered, and supportive treatments with intensive monitoring were extended to all the patients. Second-line strategies for steroid-refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab or surgery. RESULTS: The median number of Truelove criteria at admission was 3 (range 2-5), median CRP 34 mg/l (range 10-196). Median follow-up after discharge was 49 months. In 84 (57%) episodes an early response was noted, while 65 (43%) did not respond within 10 days to the standard steroid treatment. In the non-responders group, 28 patients went into remission with a prolonged steroid treatment (slow responders); 15 patients were treated with ciclosporin (eight responders) and 6 with infliximab (four responders). A total of 24 colectomies was performed in this group of patients (in 21 cases within 30 days from admission). Slow responders showed lower albumin levels (P = 0.02), higher cumulative dose of glucocorticosteroids in the year prior to admission (P = 0.02) and higher age (P = 0.03), in comparison with early responders. Major complications were noted in four episodes which responded to medical treatment. Disease-related mortality was zero. CONCLUSIONS: Medical treatment and use of second-line therapies were effective in the present series of patients. A group of slow responders has been identified and, if an intensive medical monitoring is guaranteed, steroids can be safely prolonged after the first 10 days of treatment. Cumulatively, about 80% of the patients responded to short-term medical treatment, only 5% of the patients underwent colectomy in the follow-up period. Major adverse events were recorded in four patients, who had recovered completely after adequate medical treatment.

The role of endoscopy in inflammatory bowel disease.

Endoscopy is an essential tool for diagnosis, management and prognostic evaluation of inflammatory bowel disease. However dyscomfort, potential risks and costs associated to endoscopic examinations should contribute to the narrowing of indications to those cases in which the result of endoscopy is essential to determine a variation in the management strategy. Ileocolonoscopy performed by an expert endoscopist allows accurate diagnosis of Crohn's disease or ulcerative colitis in up to almost 90% of cases. Colonoscopy has a prognostic role during a severe flare of disease (the occurrence of severe endoscopic lesions have a negative prognostic value with significantly higher risk not to respond to medical treatment) both in ulcerative colitis and in Crohn's disease; moreover in Crohn's disease the evaluation of recurrent lesions at anastomosis after curative surgery has a strong prognostic role (endoscopic recurrence closely correlates with clinical/surgical recurrence) and preliminary data suggest that mucosal healing assessed with endoscopy after biologic treatments could be associated with a better prognosis. Finally colonoscopy is essential for cancer surveillance during the long-term follow-up. Furthermore there are new endoscopic techniques under evaluation in inflammatory bowel disease, like wireless capsule endoscopy or double balloon enteroscopy for the imaging of small bowel, or endoscopic ultrasound for evaluation of strictures or of perianal disease. Finally some operative techniques like balloon dilation could possibly be employed more frequently in the future in the management of Crohn's disease. Future perspectives in endoscopy for IBD are chromoendoscopy and newer endoscopic imaging techniques, possibly leading to an "in-vivo histology".

Review article: medical treatment of severe ulcerative colitis.

Approximately 15% of patients with ulcerative colitis have a severe attack requiring hospitalization at some time during their illness. This treatment leads to a remission in 60-80% of patients and non-responders may require a total colectomy. Mortality in severe episodes of ulcerative colitis decreased from 31-61% in the 1950s to 5-9% in the 1960s thanks to the introduction of steroids and to a policy of early colectomy. Recently, some new drugs have been shown to be effective in the treatment of severe steroid-refractory ulcerative colitis. This review concentrates on the clinical evaluation, prognostic factors and new developments in medical therapy in severe ulcerative colitis. A retrospective evaluation of a consecutive series of patients with severe ulcerative colitis admitted to a Gastroenterology Department in Torino, Italy, is also reported.

Detection of anti-Saccharomyces cerevisiae antibodies in Crohn's disease: is it a reliable diagnostic and prognostic marker?

BACKGROUND: In the past few years, serologic markers have been proposed in inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies showed high specificity for Crohn's disease. A prognostic role for serology has also been hypothesised. AIMS: To evaluate anti-Saccharomyces cerevisiae antibody distribution in an unselected Italian inflammatory bowel disease population. To analyse whether anti-Saccharomyces cerevisiae antibody status (positive/negative) and/or anti-Saccharomyces cerevisiae antibody titres are associated with clinical variables and outcome measures in Crohn's disease patients. PATIENTS AND METHODS: A series of 299 inflammatory bowel disease patients were evaluated; serum samples were taken and a short clinical history was recorded. anti-Saccharomyces cerevisiae antibodies IgG enzyme-linked immunosorbent assay Medilab (Milan, Italy) kit was used in order to determine anti-Saccharomyces cerevisiae antibody status. RESULTS: Sensitivity, specificity and likelihood ratio for positive test in the differential diagnosis of inflammatory bowel disease was 59%, 89%, 8.1, respectively. Clinical variables significantly associated with anti-Saccharomyces cerevisiae antibody status in logistic regression were found to be ileal location (p=0.01) and earlier age at diagnosis (p<0.01). Among ileal Crohn's disease patients, there was a trend in concordance between anti-Saccharomyces cerevisiae antibody titres and higher number of surgical procedures which was not statistically significant applying more complex statistics. CONCLUSIONS: In an Italian inflammatory bowel disease population, anti-Saccharomyces cerevisiae antibodies status showed characteristics similar to those previously reported. Anti-Saccharomyces cerevisiae antibody positivity is associated with ileal involvement and with earlier onset of Crohn's disease.

Genotype-phenotype relationship in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases of unknown etiology. Much effort has been made in the last years to clarify the pathogenesis of inflammatory bowel disease (IBD). Data are not conclusive at the moment, but the most important known risk factor for developing IBD is a positive familial history. Genetic analyses have shown a linkage between loci on several chromosomes and IBD (IBD1 gene on chromosome 16 for CD and on chromosome 12 for UC). The association of genotype to specific phenotypes of disease could be hypothesized by the concordance of clinical characteristics in familial IBD, by the association of specific HLA haplotypes to clinically different groups of patients, and by different responses to treatment related to different polymorphisms of other chromosome 6 genes. The clinical heterogeneity of IBD has led to classifications of patients with Crohn's disease based upon clinical features (e.g. Rome and Vienna classifications) that allow the identification of subgroups of patients with similar clinical behavior. The possible drawbacks of these classifications are the lack of validation of intra-interobserver concordance, the absence of prospective evaluations, and stratification into too many subgroups. Furthermore, in our experience, clinical presentation (surgical or medical) seems to have a good correlation with prognosis, is easy identifiable, and can be applied at the time of diagnosis. In UC, extension of disease and clinical behavior correlate with prognosis. For these reasons, studies correlating genotype to phenotype should be performed to improve our knowledge of the diseases and possibly to stratify patients into different subgroups for more personalized treatments, in clinical trials and for research purposes.

Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children.

BACKGROUND: The hookworms, Ancylostoma duodenale and Necator americanus, cause significant gastrointestinal blood loss. In clinical studies, greater blood losses have been reported with A. duodenale. However, there has been no evidence that endemic A. duodenale infection has greater impact than N. americanus infection on the iron status of populations. METHODS: In a sample of 525 school children in Pemba Island, Tanzania, we compared the degree of anaemia and iron deficiency associated with the two hookworm species at the individual and community (i.e. school) levels. Multiple regression was used to control for infection intensities and other child characteristics. RESULTS: In the 492 children with hookworm positive faecal cultures, haemoglobin and ferritin concentrations decreased with increasing proportions of A. duodenale. Among children with only N. americanus larvae, the prevalence of anaemia was 60.5 % and the prevalence of ferritin <12 microg/l was 33.1%, while in children with > or =50% A. duodenale larvae, the respective prevalences were 80.6% and 58.9%. When children were grouped by the prevalence of A. duodenale at the school level, children from high prevalence (> or =20%) schools had significantly worse iron deficiency and anaemia than children from low prevalence schools. CONCLUSIONS: The species of hookworm being transmitted in a community influences the burden of iron deficiency anaemia in the community, and should be considered in prioritizing and planning programmes for hookworm and anaemia control.

PIP: Hookworms infect 1.3 billion people annually. Iron-deficiency anemia caused or exacerbated by intestinal blood loss is the major feature of hookworm infection, with such loss caused by the feeding of hookworms upon the intestinal mucosa. The hookworms Ancylostoma duodenale and Necator americanus cause major gastrointestinal blood loss. While relatively greater blood loss has been reported in clinical studies due to infection with A. duodenale, there has been no evidence that endemic A. duodenale infection has a greater impact than N. americanus infection upon the iron status of populations. The authors compared the degree of anemia and iron deficiency associated with these 2 hookworm species at the individual and community levels using a sample of 525 school children in grades 1-4 in Pemba Island, Tanzania, and controlling for infection intensities and other child characteristics through multiple regression. In the 492 children with hookworm-positive fecal cultures, hemoglobin and ferritin concentrations decreased with increasing proportions of A. duodenale. Among children with only N. americanus larvae, the prevalence of anemia was 60.5% and the prevalence of ferritin under 12 mcg/l was 33.1%. In children with 50% or higher proportions of A. duodenale larvae, the respective prevalences were 80.6% and 58.9%. Children from schools with high prevalences of A. duodenale infection had significantly worse iron deficiency and anemia than did children from low prevalence schools.

Amantadine hydrochloride decreases serum ALT activity without effects on serum HCV-RNA in chronic hepatitis C patients.

BACKGROUND AND AIMS: To investigate the effects and tolerance of amantadine in chronic hepatitis C patients. PATIENTS AND METHODS: Forty consecutive patients, with biopsy proven chronic active hepatitis, were treated with amantadine 200 mg daily in the morning for two months. Nineteen patients were previous non responders to alpha-interferon, nine patients experienced hepatitis relapse after interferon treatment, and twelve patients had never been treated with antiviral drugs. Complete blood count, liver and renal function tests were performed two months before, at baseline, end of therapy and two months after its completion. RESULTS: None of the patients experienced significant side effects. Twenty-four patients (60%) showed a reduction of serum aminotransferase levels (twelve patients > 30% and twelve patients < 30% of their basal levels). The analysis of variance showed a significant reduction in aminotransferase levels at the end of treatment (F = 11, p < 0.0001). In four patients, aminotransferases returned to normal, but none of them cleared HCV-RNA. After the end of treatment, serum ALT returned to baseline values in all patients. CONCLUSIONS: Amantadine is well tolerated in chronic hepatitis C patients. The time-relation between therapy and reduction of serum aminotransferase levels in 60% of patients suggests a potential anti-inflammatory activity of the drug without an effect on viraemia.

Pre-treatment levels of anti-HCV core IgM antibodies are closely associated with response to alpha interferon therapy in chronic hepatitis C patients.

OBJECTIVES: To investigate the relationship between pre-treatment levels of anti-hepatitis C virus (HCV) immunoglobulin M (IgM) antibodies and the outcome of interferon therapy, and also the relationship with genotypes and quantitative viraemia. PATIENTS: One hundred and four patients with biopsy-proven chronic hepatitis C without cirrhosis, consecutively enrolled in three general hospitals in Turin, Italy, and treated according to the same interferon schedule (3 MU of recombinant alpha-2b interferon three times a week for 6 months). Anti-HCV IgM were measured by a second-generation enzyme-linked immunoassay and results expressed as sample-cutoff ratio. In 30 patients, determination of viraemia by branched DNA (bDNA) and genotyping were performed and the correlation with anti-HCV IgM ratios was assessed. RESULTS: According to univariate analysis, anti-HCV IgM ratios, age, serum gamma-glutamyltranspeptidase (gamma-GT) and ferritin levels were significantly associated with sustained response to therapy. A log-linear model, testing the effect of these variables on response to therapy, showed that anti-HCV IgM ratio was the only independently associated variable (P=0.00057). Anti-HCV IgM were associated with viraemia levels (r=0.57), but not with genotype distribution. Patients with anti-HCV IgM ratio less than 1 were sustained responders to the 'standard therapy' in 65% of cases. By contrast, among patients with a ratio greater than 3, sustained response was achieved in only one patient (3%), while 73% were non-responders; the majority of relapsers were found among patients with a ratio between 1 and 3. CONCLUSION: Anti-HCV IgM antibodies provide an easily accessible and cheap serological marker of active viral replication, and are significantly related to the outcome of interferon therapy in patients with chronic hepatitis C.

Rate of reinfection with intestinal nematodes after treatment of children with mebendazole or albendazole in a highly endemic area.

The comparative efficacy of albendazole and mebendazole in the treatment of intestinal nematode infections were compared 3 weeks after treatment in a randomized trial among schoolchildren on Pemba Island, Tanzania. Egg counts were compared 3 weeks, 4 months and 6 months after treatment of 731 children seen on each occasion. Differences in the efficacies were apparent with some nematodes 21 d after treatment, but these were no longer apparent 4 months after treatment, and by 6 months intensities of infection were similar to pre-treatment levels. These findings suggest that treatment of schoolchildren every 4 months may be necessary in this highly endemic area in order to have an impact on the intensity of intestinal nematode infections sufficient to be likely to reduce morbidity.