H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amoxicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.
The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.Melanoma, a highly malignant tumor of the pigmented cells, is a significant worldwide health concern. The 5-year survival for patients with involvement of regional lymph nodes is 35%, with fewer than 2% of patients with visceral metastatic disease alive at 5 years. Therapy with interferon alpha-2b (IFNalpha-2b), the only agent approved in the United States for adjuvant use in high-risk melanoma patients, has not shown consistent overall survival benefit in randomized trials and is associated with considerable toxicity. Conventional chemotherapy for unresectable metastatic disease does not improve survival, while patients with completely resected metastatic disease have a median survival of <20 months. Since there is clearly a need for more effective therapies in these high-risk patients and because steps towards new effective therapies against melanoma are currently being taken, we will focus on melanoma therapies to highlight the new immunotherapy strategies.While there is good reason to question the effectiveness of the host response against spontaneously arising tumors, there is clear evidence that specific immune cells are recruited to tumor sites. In fact, lymphocytic infiltration of tumors was first observed by Rudolf Virchow in 1863, before
Since the first reports almost ten years ago, wireless capsule endoscopy has gained new fields of application. Colon capsule endoscopy represents a new diagnostic technology for colonic exploration. Clinical trials have shown that colon capsule endoscopy is feasible, accurate and safe in patients suffering from colonic diseases and might be a valid alternative to conventional colonoscopy in selected cases such as patients refusing conventional colonoscopy or with contraindications to colonoscopy or when colonoscopy is incomplete. Despite the enthusiasm surrounding this new technique, few clinical and randomized controlled trials are to be found in the current literature, leading to heterogeneous or controversial results. Upcoming studies are needed to prove the substantial utility of colon capsule endoscopy for colon cancer screening, especially in a low prevalence of disease population, and for other indications such as inflammatory bowel disease. Possible perspectives are critically analysed and reported in this paper.
Hepatitis C VIrUS (HCV) often has a more favorable course in younger patients. Considering the involution ofthe thymic function with age, we investigated the output of recent thymic emigrants (RTE) in HCV patients. To evaluate RTE, we used a competitive quantitative PCR in order to determine the percentages of cells with cj-T cell receptor excision circles (TREC). This study was performed in 14 HCV patients at diagnosis and before any anti-HCV treatment. The results obtained in this group were compared to those obtained in a group of age-matched controls. We found that in the 14 HCV patients naive for anti-HCV treatment the mean percentage of cj-TREC was 3%. We could not detect a correlation between the percentages of cj-TREC and age or patients' viremia. In contrast, in the 26 age-matched controls mean percentage of cj-TREC was 5.6% (P=O.OI). Our study describes a novel immune defect in HCV patients. Additional studies are needed to get further insight in the possible role ofTREC defect in the pathogenesis and prognosis ofthe disease.Hepatitis C virus infection (HCV) is a major issue in world public health, affecting approximately 2% of the world's population (1). The infection has a variable clinical course. The outcome has been related to the evolution of the viral quasispecies (2). Since HCV replicates in lymphatic tissue, several immunological disorders, linked to persistent antigenic stimulation, are associated to patients with chronic active hepatitis. Apart from the viral factors, the immune mechanisms responsible for the highly variable natural history in a given patient are only partially known. Some reports have pointed out a more favorable prognosis in younger patients (3-4). T-lymphocytes are of pivotal importance in host defense against viruses. T-cells are produced in the thymus and this organ undergoes a physiological involution with age.In the last decades, it became possible to evaluate the thymic output, measuring the T-cell receptor excision circles (TREC) present in the so called "recent thymic emigrants" (RTE) (5-6). TREC are DNA fragments representing a byproduct of T-cell receptor rearrangement; there are at least two possible molecules, named coding-joint (cj) and signal-joint (sj) TREC, each of which is produced in a defined moments of the intrathymic maturation of T cells. Since their DNA exists in a circular form, they are not duplicate during mitosis, but progressively diluted in peripheral blood T-cells. TREC are present only in virgin cells, i.e. those newly produced in the thymus, and thus their measurement allows the determination ofRTE. These cells have been proved to be altered in several clinical conditions, with clinical and prognostic implications (7-9).For these reasons, we aimed to verify the hypothesis of thymic impairment in patients with HCV infection by analysis of means of RTE in a prospective case-control study. 0394-6320 (2005) Copyright© by BIOLIFE,s.a.s. This publicationand/orarticleis for individualuse only and may not be further reproducedwithoutwrittenpermi...
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