Leishmania braziliensis ssp. in the nasal mucosa of guinea pigs inoculated in the tarsi

Two lots of 20 young male guinea pigs were inoculated subcutaneously in the tarsi with 10 (elevated to fourth potency) amastigotes of Leishmania braziliensis or L. b. guyanensis to study the susceptibility of this Neotropical hystricomorph rodent the autochthonous parasites. Almost 50% of the animals showed lesions in the inoculation site and had parazitations that were infective to hamsters, as shown by inoculating homogenates of the dermal lesion, of the spleen, of the liver, and of the nasal mucosa into hamsters at 20, 40, 60 and 120 days after inoculation of the guinea pig. Smears of the above organs showed the presence of amastigotes. Parasites inoculated into the tarsi were detected early in the skin, spleen, and liver of the guinea pig host. Blood cultures made by cardiopuncture on sacrifice of the guinea pigs were uniformly negative. The nasal mucosa of nearly all animals positive in the skin or viscera was invaded early by the parasites, although with grater frequency between 60 and 120 days post-inoculation. The use of this model for the study of mucocutaneous parasitism by L. brasiliensis is discussed, together with the phenomena of parasitism at a distance from the inoculation site, the temperature of the body regions affected, and the possible genetic influence on susceptibility of the guinea pig to L. brasiliensis.

Epithelium-Intrinsic NAIP/NLRC4 Inflammasome Drives Infected Enterocyte Expulsion to Restrict Salmonella Replication in the Intestinal Mucosa.

The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.

Pseudomonas aeruginosa adhesion to normal and injured respiratory mucosa

Human nasal polyps outgrowth culture were used to study the adhesion of Pseudomonas aeruginosa to respiratory cells. By transmission electron microscopy, bacteria associated with ciliated cells were identified trapped at the extremities of cilia, usually as aggregates of several bacterial cells. They were never seen at the interciliary spaces or attached along cilia. Bacteria were also seen to adhere to migrating cells of the periphery of the outgrowth culture. Using a model of repair of wounded respiratory epithelial cells in culture, we observed that the adhesion of P. aeruginosa to migrating cells of the edges of the repairing wounds was significantly higher than the adhesion to non-migrating cells and that adherent bacteria were surrounded by a fibrocnectin-containing fibrillar material The secretion of extracellular matrix components is involved in the process of epithelium repair following injury. To investigate the molecular basis of P. aeruginosa adhesion to migrating cells, bacteria were treated with a fibronectin solution before their incubation with the respiratory cells. P. aeruginosa treatment by fibronectin significantly increased their adhesion to migrating cells. Accordingly, we hypothesize that during cell migration, fibronectin secreted by epithelial cells may favour P. aeruginosa adhesion by establishing a bridge between the bacteria and the epithelial cell receptors. Such a mechanism may represent a critical step for P. aeruginosa infection of healing injured epithelium.

Gastrointestinal immune responses in HIV infected subjects

The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

A case of oesophageal cancer limited to the mucosa and submucosa

The authors report a case of an oesophageal cancer limited to the mucosa and the submucosa. This case is interesting because of its long history for more than 18 months, the difficulty of fiberoptic diagnosis and the diagnostic value of rigid instruments completed via vital staining by o-toluidine.

Patients' preferences on information and involvement in decision-making for gastrointestinal surgery

Objective: The relationship between physicians and patients has undergone¦important changes, and the current emancipation of patients has led to¦a real partnership in medical decision-making. This study aimed to assess¦patients' preferences on different aspects of decision-making during treatment¦and potential complications, as well as the amount and type of preoperative¦information before visceral surgery.¦Methods: Prospective non-randomized study based on a questionnaire given¦to 253 consecutive patients scheduled for elective GI surgery.¦Results: Concerning surgical complications or treatment in the intensive care¦unit, 64% of patients wished to take actively part in any medical decisions.¦The respective figures for cardiac resuscitation and treatment limitations were¦89% and 60%. About information, 73%, 77% and 47% of patients wish¦detailed information, information on a potential ICUhospitalization and cardiac¦resuscitation, respectively. Elderly and low-educated patients were significantly¦less interested in shared medical decision-making (p = 0·003 and 0·015) and in¦information receiving (p = 0·03 and 0·05). Similarly, involvement of the family¦in decision-making was significantly less important in elderly and male patients¦(p = 0·05 and 0·03 respectively). Neither the type of operation (minor or major)¦nor the severity of disease (malignancies vs. non-malignancies) was a significant¦factor for shared decision-making, information or family involvement.¦Conclusion: The vast majority of surgical patients clearly want to get adequate¦preoperative information about their disease and the planned treatment. They¦also consider it as crucial to be involved in any kind of decision-making for¦treatment and complications. The family's role is limited to support the treating¦physicians if the patient is unable to participate in taking decisions.

Female-biased infection and transmission of the gastrointestinal nematode Trichuris arvicolae infecting the common vole, Microtus arvalis.

Previous studies addressing the importance of host gender in parasite transmission have shed light on males as the more important hosts, with the higher transmission potential of males being explained by the fact that they often harbour higher parasite loads than females. However, in some systems females are more heavily infected than males and may be responsible for driving infection under such circumstances. Using a wild population of common voles (Microtus arvalis), we showed that females were more frequently infected by the intestinal nematode Trichuris arvicolae than males (i.e. prevalence based on the presence of eggs in the faeces) and that females were shedding greater numbers of parasite eggs per gram of faeces (EPG) than males. By applying an anthelmintic treatment to either male or female voles, we demonstrated that treating females significantly reduced parasite burdens (i.e. prevalence and EPG) of both male and female hosts, while treating males only reduced parasite burden in males. These findings indicate that in this female-biased infection system females play a more important role than males in driving the dynamics of parasite transmission.

Treatment of gastrointestinal stromal tumor after imatinib and sunitinib.

Purpose of review Tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, have changed the outcome of patients with gastrointestinal stromal tumor (GIST) and prolonged survival by many-fold. Unfortunately, treatment failure and tumor progression seem inevitable over time and constitute an unresolved clinical challenge. This article reviews current efforts to overcome drug resistance and progression. Recent findings The major mechanism of resistance toward imatinib and sunitinib is the development of secondary resistance mutations in the kinase domain of KIT. Recent efforts aim at inhibitors with increased activity against resistance mutations or a broader spectrum of activity. Other strategies include indirect KIT inhibition by modulating KIT chaperone proteins or inhibition of KIT-dependent and independent signaling pathways. Summary dThe rapid improvement of our understanding of GIST biology as well as resistance mechanisms towards imatinib and sunitinib will greatly facilitate the development of novel treatment strategies. This article summarizes the results of recently reported third and fourth-line clinical trials in patients with resistant GIST and reviews data of important proof-of-concept studies.

Monitoring of vaccine-specific gamma interferon induction in genital mucosa of mice by real-time reverse transcription-PCR.

Monitoring of T-cell responses in genital mucosa has remained a major challenge because of the absence of lymphoid aggregates and the low abundance of T cells. Here we have adapted to genital tissue a sensitive real-time reverse transcription-PCR (TaqMan) method to measure induction of gamma interferon (IFN-gamma) mRNA transcription after 3 h of antigen-specific activation of CD8 T cells. For this purpose, we vaccinated C57BL/6 mice subcutaneously with human papillomavirus type 16 L1 virus-like particles and monitored the induction of CD8 T cells specific to the L1(165-173) H-2D(b)-restricted epitope. Comparison of the responses induced in peripheral blood mononuclear cells and lymph nodes (LN) by L1-specific IFN-gamma enzyme-linked immunospot assay and TaqMan determination of the relative increase in L1-specific IFN-gamma mRNA induction normalized to the content of CD8b mRNA showed a significant correlation, despite the difference in the readouts. Most of the cervicovaginal tissues could be analyzed by the TaqMan method if normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA was used and a significant L1-specific IFN-gamma induction was found in one-third of the immunized mice. This local response did not correlate with the immune responses measured in the periphery, with the exception of the sacral LN, an LN draining the genital mucosa, where a significant correlation was found. Our data show that the TaqMan method is sensitive enough to detect antigen-specific CD8 T-cell responses in the genital mucosa of individual mice, and this may contribute to elaborate effective vaccines against genital pathogens.

Estudi de l’efecte del tractament amb Adalimumab sobre la microbiota associada a la mucosa intestinal en pacients amb malaltia de Crohn.

La malaltia de Crohn és una malaltia inflamatòria intestinal en la qual s´ha observat que la densitat i la diversitat bacteriana difereixen dels subjectes sans. En els últims anys s’estan emprant tractaments biològics com els anti-TNFα (Adalimumab) de manera alternativa a tractaments ja existents. Els resultats obtinguts després de l’anàlisi de la composició bacteriana de la mucosa intestinal de pacients amb Malaltia de Crohn tractats amb Adalimumab, són esperançadors ja que apunten a una recuperació del patró normal a través de la recuperació d’espècies pròpies de persones sanes i la desaparició d’aquelles més prevalents en malalts de Crohn.

Aspects of gastrointestinal immunology and nutrition in human immunodeficiency virus-1 infection in Brazil

Mucosal surfaces have a fundamental participation in many aspects of the human immunodeficiency virus (HIV) infection pathogenesis. In Brazilian HIV-1 infected subjects, loss of weight and appetite are among the most debilitating symptoms. In this review we describe a defined mucosal immunogen that has profound but transient effects on HIV viral load, and we suggest that gut associated lymphoid tissue under constant immunostimulation is likely to provide a major contribution to the total levels of HIV. We also show that hypermetabolism appears to play a role in the wasting process in Brazilian patients coinfected with HIV and tuberculosis.

Underutilization of upper gastrointestinal endoscopy.

BACKGROUND & AIMS: Efforts to reduce costs in health care may raise concerns about underuse of medical procedures. This study prospectively assessed underuse of upper gastrointestinal endoscopy in a cohort of patients in whom we have recently published data on overuse of endoscopy. METHODS: Underuse was identified by formal necessity criteria for endoscopy, obtained by an explicit panel process. Outpatients were consecutively included in two clinical settings. Setting A consisted of 20 primary care physicians and 7215 patient visits that occurred within 1 month. Setting B consisted of 920 visits that occurred during 3 weeks at an outpatient clinic. RESULTS: During these 8135 visits, 611 patients complained of upper digestive symptoms; 63 of them underwent endoscopy. Underuse was identified in 72 patients (11.8%). The two clinical situations mainly responsible for underuse of endoscopy were uninvestigated peptic symptoms resistant to treatment and dysphagia. At first follow-up, 29 of the patients with initial underuse still fulfilled criteria of necessity (underuse rate, 4.7%). One-year follow-up showed underuse of endoscopy in 5 patients. CONCLUSIONS: This prospective evidence shows that underuse of a medical procedure exists. The estimated overuse and underuse of endoscopy in this cohort were approximately equal (5%). Improving quality of care will require reductions of both overuse and underuse of medical procedures.

Protocolo diagnóstico y seguimiento de la prevalencia e incidencia del virus del papiloma humano (vph) y las anormalidades citológicas de la mucosa anal de hombres que tienen sexo con hombres (hsh) e infección por el virus de la inmunodeficiencia humana (vih).

La citologia anal és un mètode sensible en el despistatge de la neoplàsia de canal anal i similar a la biòpsia dirigida mitjançant rectoscopi i tinció amb àcid acètic al 5%, sobretot en lesions d’alt grau de malignitat; a més de ser una prova adequada en el seguiment d’aquestes lesions. Els pacients VIH homes que tenen sexe amb altres homes tenen major incidència i prevalència de virus papiloma humà i major nombre d’anormalitats en la mucosa del canal anal que els VIH negatius.

Use of polymerase chain reaction and enzymatic cleavage in the identification of Helicobacter spp. in gastric mucosa of human beings from North Paraná, Brazil

Helicobacter pylori is the most common gastric bacteria of human beings. Animal-borne helicobacter have been associated with gastritis, ulceration, and gastric mucosa-associated lymphoid-tissue lymphoma in people. We attempted to identify the species of Helicobacter spp. that infect human beings in north Paraná, Brazil. Samples of gastric mucosa from 38 dyspeptic patients were analyzed by optic microscopy on silver stained slides, polimerase chain reaction (PCR), and enzymatic cleavage. Genus and species-specific primers to H. pylori, H. heilmannii, H. felis, and consensual primers to H. bizzozeronii or H. salomonis were used. The PCR products were submitted to enzymatic cleavage by VspI (Helicobacter spp. product) and HinfI (species products) enzymes. Thirty-two out of 38 patients evaluated had 3.2 to 5 µm long bacteria that resembled H. pylori in Warthin-Starry stained slides and were positive to the genus Helicobacter by PCR. In 30 of these patients the bacteria were identified as H. pylori. Two samples positive by silver stain were negative to all species tested by PCR. None of the 38 samples was positive to animal-origin helicobacter species. These results show that PCR and enzymatic restriction are practical methods to identify the species of helicobacters present in gastric mucosa of human beings. People in north Paraná appear to be infected mostly with H. pylori.

Foodborne infections & gastrointestinal disease on the island Of Ireland in 2002

A safefood consultation paper, ‘Towards the Enhancement of Foodborne Disease Surveillance’ indicated that the guiding principles for the development of surveillance in Northern Ireland and the Republic of Ireland should be the integration of data collection systems and analysis of combined data. The current surveillance systems have developed independently from each other and clinical, food and animal surveillance systems remain un-integrated in both jurisdictions. A more complete and efficient food safety system could be achieved through co-ordination and linkages across the disease surveillance systems and jurisdictions. For that reason, stronger links are being developed between safefood, surveillance agencies, government departments and public health professionals. This report is an examination and review of the clinical surveillance data collected in both jurisdictions. The work was undertaken as part of safefood’s support for the European Programme for Intervention Epidemiology Training (EPIET), which trains EU medical practitioners, public health nurses, microbiologists or veterinarians in all aspects of foodborne disease surveillance.