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P Michetti

Publications and source records attributed to P Michetti.

At least 37 records · Page 2Linked to original sources
PubMed2001

Vaccines: an ongoing promise?

Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed.

Animals↗
PubMed2001

Vaccination against Helicobacter pylori--an old companion of man.

Helicobacter pylori infection induces an important systemic and mucosal antibody response and a predominant Th1 cellular response. These immune responses, although powerful, fail to eliminate the infection. Studies in animals have shown that prophylactic and therapeutic immunisations are efficacious, although complete protective immunity has usually not been achieved. Initial human trials with recombinant urease showed that a mucosal immune response can be obtained following immunisations, with a decrease in bacterial density, but successful immunisation is still awaited. Progress is being made in several areas of vaccine design. A human vaccine against H. pylori would be favourable in terms of health benefits and costs in developed and developing countries.

Animals↗
PubMed2000

Laparoscopically assisted ileocolectomy for Crohn's disease through a pfannenstiel incision.

Recently, laparoscopically assisted bowel resections have been shown to be less morbid than the traditional laparotomy, especially for benign conditions such as Crohn's disease. While reports describing laparoscopically assisted bowel resections use a small midline or right transverse incision, we describe a novel laparoscopically assisted approach employing a Pfannenstiel incision for Crohn's patients. We attempted the Pfannenstiel incision since it is well known to be associated with less postoperative pain, decreased ileus and hospital stay, and low rates of wound infection and incisional hernia, compared with midline or right transverse incisions. Furthermore, we found that the Pfannenstiel incision offers additional advantages that may be uniquely suited for Crohn's patients. First, the cosmetic position of the incision is particularly attractive to the young population affected by Crohn's. Second, the Pfannenstiel incision preserves fresh tissue in the midline, right, and left lower quadrants in the event that reoperation or stoma placement are required in the future owing to recurrent disease. We describe our technique in 10 consecutive patients undergoing ileocolectomy for Crohn's disease. Our patients experienced minimal morbidity and were pleased with the cosmetic results of their incisions.

Adult↗
PubMed2000

Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice.

Homeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)-induced colitis. Sonicates of Gram-positive, Gram-negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1 mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1-14); median (range)) compared with PBS-fed control animals (15 (7-19); P < 0.05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6-11); P < 0.05 versus control), but not in mice fed a pool of Gram-positive and -negative sonicates (16 (12-16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS-fed control animals. DSS-induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.

Acute Disease↗
PubMed2000

Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against helicobacter infection in mice.

BACKGROUND & AIMS: The integrin alpha(4)beta(7) mediates homing of effector/memory lymphocytes to the intestine and the mucosa-associated lymphoid tissue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T lymphocytes to home to the stomach and their role in immunization-mediated protection against Helicobacter felis infection. METHODS: Gastric lamina propria and circulating mononucleated cells of naive, infected, and immunized Swiss Webster mice were isolated, and alpha(4)beta(7)-integrin expression was quantified by flow cytometry on CD4(+) T lymphocytes. Anti-alpha(4)beta(7)-integrin antibody was used to block alpha(4)beta(7) function in vivo. RESULTS: In naive mice, alpha(4)beta(7)(hi) CD4(+) T cells were enriched approximately 10-fold in the gastric mucosa compared with peripheral blood (P<0.0001). Chronic H. felis infection did not alter these proportions, but oral immunization with H. felis sonicate plus cholera toxin (CT) or with CT alone markedly increased gastric alpha(4)beta(7)(hi) CD4(+) T cells compared with naive and infected controls (P = 0.0008 and P = 0.002 for H. felis sonicate and CT, respectively). Anti-alpha(4)beta(7)-integrin antibody blocked the protection induced by oral immunization with H. felis sonicate and CT. CONCLUSIONS: The integrin alpha(4)beta(7) participates in the homing of CD4(+) T lymphocytes to the stomach and in the protection of the gastric mucosa against H. felis infection.

Administration, Oral↗
PubMed2000

Clinical experience with infliximab therapy in 100 patients with Crohn's disease.

OBJECTIVE: The aim of this study was to assess our clinical experience with infliximab, a monoclonal antitumor necrosis factor antibody, following its approval for treatment of refractory Crohn's disease (CD). METHODS: We followed 100 consecutive patients with CD (53 women and 47 men; mean age, 41 yr) who received a total of 233 infliximab (5 mg/kg) infusions. Adverse events were noted and clinical response assessed every 2 wk for 6 months after each infusion using the Harvey Bradshaw Index (HBI) for active disease, the Perianal Disease Activity Index (PDAI) for fistulous disease, and steroid withdrawal rates for steroid-sparing efficacy. RESULTS: Indications for therapy were active disease (n = 57), perianal fistulous disease (n = 33), and steroid dependency (n = 10). Significant infusion reactions occurred in 16 patients (6.9% of infusions) including anaphylactic shock in one patient. Fourteen patients experienced infectious adverse events, 13 of whom were on concurrent steroids. Sixty percent of patients with active disease experienced > or = 50% HBI reduction at 2 wk; mean duration of response, 8.2 wk. Three of 26 first-time nonresponders with active disease (12%) responded to a second infusion. Sixty-nine percent of patients with fistulous disease experienced >50% reduction in their PDAI at 2 wk; mean duration of response, 10.9 wk. Four of 10 steroid-dependent patients (40%) discontinued steroid therapy, one of whom recommenced steroid therapy at 24 wk. CONCLUSIONS: Our clinical response rates mirror the efficacy reported in the controlled trials for active and fistulous disease. Steroid-sparing efficacy was seen in 40% of steroid-dependent patients. Concurrent steroids did not reduce the risk of significant infusion reactions (6.9%), but did increase the risk of infections.

Adult↗
PubMed1999

Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.

BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.

Administration, Oral↗
PubMed1999

Medical therapy of specific clinical presentations.

A pluridisciplinary approach that integrates medical therapy with surgery and other aspects of patient care, such as nutritional and psychosocial support, is essential to the management of patients with inflammatory bowel disease (IBD). Despite new medical therapies, such as 5-amino-salicylic acid compounds, steroids, and immunomodulators, the treatment of patients with IBD remains challenging. Success depends on the appropriate use of the available medications in relation to the severity and localization of the disease. The introduction of novel immunomodulating agents such as antitumor necrosis factor alpha is likely to have a major influence on the current therapeutic strategies. This article describes the use of the available medications in the most common clinical presentations of IBD.

Adrenal Cortex Hormones↗
PubMed1999

Strategies for developing a Helicobacter pylori vaccine.

Novel strategies are needed to control infection with Helicobacter pylori. Prophylactic and therapeutic immunization against this gastric pathogen is possible in animal models, and initial human studies in H. pylori-infected subjects showed that immunization with H. pylori urease is both safe and immunogenic. In rodents, gastric protection against Helicobacter species infection does not depend on the humoral immune response, and a prominent role of the major histocompatibility complex II-restricted CD4(+) T-cell response is recognized; however, much remains to be learned about the mechanisms of effective bactericidal response. A clear understanding of the basic mechanisms of gastric immune protection in humans is of the utmost importance for the development of an effective human vaccine. More potent vaccines are likely to be required to induce protection in humans. The availability of two complete genome sequences of H. pylori represents a unique opportunity to identify novel vaccine antigens. Multivalent vaccines delivered by recombinant attenuated bacteria or administered with nontoxic adjuvants need to be evaluated in relevant models.

Journal Article↗
PubMed1999

Mesalamine-associated thrombocytopenia.

We describe a case of a 25-yr-old woman with ulcerative colitis who developed marked thrombocytopenia during treatment and upon rechallenge with oral mesalamine. In contrast to its parent drug, sulfasalazine, which has often been reported to cause serious blood disorders, particularly agranulocytosis, mesalamine has rately been implicated as a cause of serious blood disorders. Although previous cases of hematological toxicity have been described in patients taking mesalamine, none of these patients were rechallenged in an effort to prove causality between 5-aminosalicyclic acid and the hematological abnormality as well as outrule the possible "autoimmune" contribution of inflammatory bowel disease to the hematological toxicity of these agents. This report demonstrates that mesalamine has the potential, like sulphasalazine, to cause marked thrombocytopenia in an idiosyncratic fashion. All patients receiving mesalamine therapy, either orally or topically should have regular, complete blood profiles.

Adult↗
PubMed1999

Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans.

BACKGROUND: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. acidophilus can survive transiently in the human stomach, it may downregulate Helicobacter pylori infection. METHODS: The ability of L. acidophilus (johnsonii) La1 supernatant to interfere with H. pylori bacterial growth, urease activity, and adhesion to epithelial cells was tested in vitro. Its effect on H. pylori infection in volunteers was monitored in a randomized, double-blind, controlled clinical trial, using a drinkable, whey-based, La1 culture supernatant. H. pylori infected volunteers were treated 14 days with 50 ml of La1 supernatant four times a day combined with either omeprazole 20 mg four times a day or with placebo. Infection was assessed by breath test, endoscopy, and biopsy sampling, performed at inclusion, immediately at the end of the treatment (breath test only), and 4 weeks after the end of the treatment. RESULTS: La1 supernatant inhibited H. pylori growth in vitro, regardless of previous binding of H. pylori to epithelial cells. In 20 subjects (8 females, 12 males, mean age 33.1 years) a marked decrease in breath test values was observed immediately after treatment with La1 supernatant, both in the omeprazole and in the placebo group (median 12.3 vs. 28.8 and 9.4 vs. 20.4, respectively; p < 0.03). In both treatment groups, breath test values remained low 6 weeks after treatment (omeprazole treated 19.2, placebo treated 8. 3; p < 0.03 vs. pretreatment), but the persistence of H. pylori infection was confirmed in gastric biopsies. CONCLUSION: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.

Adolescent↗
PubMed1998

Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection.

BACKGROUND & AIMS: Infection with Helicobacter induces a T helper type 1 response in mice and humans. Mice can be cured or protected from infection with Helicobacter by mucosal immunization with recombinant H. pylori urease B subunit (rUreB). This study characterizes the immune response of infected mice immunized with rUreB. METHODS: BALB/c mice were infected with H. felis. Two weeks later, they were orally immunized four times with rUreB and cholera toxin (CT) at weekly intervals. Controls were only infected or sham-immunized with CT. Animals were killed at various times after immunization. Splenic CD4(+) cells were obtained and cultured in vitro with rUreB to evaluate antigen-specific proliferation and induction of interferon gamma and interleukin 4 secretion. RESULTS: All rUreB-immunized mice (n = 8) were cured from infection 3 weeks after the fourth immunization. Immunization induced a proliferative response of splenic CD4(+) cells, a progressive decrease in interferon gamma secretion, and a concomitant increase in interleukin 4 secretion after each immunization. A simultaneous increase in rUreB specific serum immunoglobulin G1 levels was observed in infected/immunized mice. CONCLUSIONS: In BALB/c mice, therapeutic mucosal immunization with rUreB induces progressively a Th2 CD4(+) T cell response resulting in the elimination of the pathogen.

Animals↗
PubMed1998

Development of a vaccine against Helicobacter pylori infection.

In animals, oral immunization can prevent or cure Helicobacter pylori infection, and prevent reinfection. Several antigens of the pathogen have been identified as protective antigens, and some appear to be well suited for use in an human vaccine. Initial clinical studies have shown that urease is safe in humans, and immunogenic in Helicobacter pylori-infected volunteers. The design of a protective vaccine in humans will probably depend upon the combination of two or more antigens, the identification of the optimal route of immunization, and the use of appropriate vaccine delivery systems. Because a vaccine against Helicobacter pylori is likely to be effective regardless of the mode of transmission of the infection, it represents a potential alternative to current therapies, with the added advantage of having a direct impact on the reservoir of the infection.

Animals↗
PubMed1998

Oral immunization against Helicobacter pylori--a future concept.

The demonstration that oral immunization with lysates of Helicobacter or with Helicobacter pylori urease can protect mice against H. felis infection opened the field of vaccine development against Helicobacter infections. More recently, the same antigen preparations were used successfully as a therapeutic vaccine able to cure the infection, and additional protective antigens were identified. Evidence from animal studies suggests that protection is medicated by mucosal antibodies, in association with a T helper type 2 cell cellular immune response. Vaccine adjuvants, delivery systems, and therapeutic vaccination are likely to be the areas of major progress in the future.

Animals↗
PubMed1997

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

Adult↗