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J C Delchier

Publications and source records attributed to J C Delchier.

At least 19 recordsLinked to original sources

Duodenal mucosa-associated lymphoid tissue lymphoma: treatment with oral cyclophosphamide.

Small cell mucosa-associated lymphoid tissue (MALT) lymphomas rarely affect the duodenum, and optimal treatment has not been defined. The aim of this case series was to determine the clinical features and outcome of duodenal MALT lymphoma in four patients (three men, one woman; median age 52 yr) treated with cyclophosphamide p.o. Initial manifestations were abdominal pain (n = 4), vomiting (n = 2), and an obstructive syndrome (n = 1). MALT lymphoma was diagnosed on the basis of endoscopic biopsies. It was localized in the duodenum in three cases and involved the entire small bowel in one case. Tumor infiltration was limited to the duodenal wall in one case and was associated with locoregional lymphadenopathy in three cases. The patients were graded EI (n = 1) and EII1 (n = 3), respectively, according to the Ann Arbor classification revised by Musshof. Cyclophosphamide, 100 mg daily, was administered p.o. for 18 months. Gastroscopy with biopsies, radiography of the small intestine and abdominal CT (CT) were performed every 6 months. Complete remission was defined by morphological and histological normalization, and partial remission as morphological normalization only. Follow-up lasted from 9 to 65 months. Three patients were in complete remission at 18 months: two relapsed after 2 yr and one was still in complete remission at 65 months. The patient with 9 months of follow-up was in complete remission at 6 months. The two patients who relapsed did not complain of symptoms, and no morphological abnormalities were seen. Relapse was diagnosed on histological grounds. Cyclophosphamide monotherapy p.o. thus seems well adapted to this slowly progressive disease, but it is unclear whether it should be resumed in the case of histological relapse or only in the case of symptomatic relapse. (Am J Gastroenterol 2000;95:536-539. (O 2000 by Am. Coll. of Gastroenterology)

Administration, Oral

Frequent association between alteration of the rdxA gene and metronidazole resistance in French and North African isolates of Helicobacter pylori.

Mutations in the rdxA gene have been associated with the acquisition of resistance to metronidazole in Helicobacter pylori. This gene encodes an NADPH nitroreductase whose expression is necessary for intracellular activation of the drug. We wished to examine whether mutations in rdxA were present in resistant H. pylori isolates infecting either French or North African patients. We determined the complete nucleotide sequences of the rdxA genes from seven French and six North African patients infected with paired resistant and sensitive strains. Genotyping by random amplified polymorphic DNA analysis confirmed the close genetic relatedness of the susceptible and resistant isolates from individual biopsies. Eight French and five North African individual resistant strains were also studied. For the French strains, an alteration in rdxA most probably implicated in resistance was found in 10 cases (seven frameshift mutations, two missense mutations, and one deletion of 211 bp). One to three putative missense mutations were identified in four cases, and a missense mutation possibly not implicated in resistance was discovered in the last case. For the North African strains, an alteration in rdxA was found in eight cases (three frameshift mutations, three missense mutations, one deletion of 6 bp, and one insertion of a variant of IS605). Two strains contained putative missense mutations, and no change was observed in rdxA of the last strain. Thus, inactivation of the rdxA gene is frequently, but not always, associated with resistance to metronidazole in French and North African clinical isolates of H. pylori. In addition, a variety of alterations of rdxA are associated with the resistant phenotype.

Africa, Northern

Oral Crohn disease: clinical characteristics and long-term follow-up of 9 cases.

BACKGROUND: Oral localization of Crohn disease is uncommon and must be differentiated from nonspecific lesions. Its natural course and its long-term prognosis are unknown. OBSERVATIONS: We studied 9 patients (8 male, 1 female; age range, 7-52 years; median age, 16 years) with Crohn disease and specific oral lesions, including deep linear ulcers, pseudopolyps, and/or labial or buccal swelling and induration. The prevalence of such lesions was 0.5%. The median follow-up was 11 years. Oral localization developed before (n = 2), at the same time as (n = 2), or after (n = 5) the onset of the digestive disease. Noticeable associated localizations were observed in the anoperineum (n = 8) and the esophagus (n = 3). The median duration of the oral lesions was 4 years (range, 1-13 years), without necessary parallelism with the digestive localization. Five patients had complete healing after a median delay of 2 years. CONCLUSIONS: Oral localization of Crohn disease is characterized by a marked male predominance, a young age at onset of Crohn disease, and a very protracted course. The high prevalence of associated anal and esophageal involvement suggests that Crohn lesions have a particular trophicity for squamous cell epithelium.

Adolescent

Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivity against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa.

BACKGROUND: It has been suggested that Helicobacter pylori may induce more or less severe gastroduodenal disease according to the strain virulence. DESIGN: We used Western blot to determine antigenic profiles associated with duodenal or gastric ulcer disease, MALT lymphoma and non-ulcer dyspepsia, and to identify geographical differences. METHODS: One hundred and eighty-two consecutive patients with H. pylori infection were studied. H. pylori infection was diagnosed by a rapid urease test or histological examination of gastric biopsy samples. Bacterial density and gastritis were assessed histologically by using the Sydney scoring system. Western blot was used to identify antibodies against eight antigens (CagA, VacA, urease A, heat shock protein B, and 19.5, 26.5, 30 and 35 kDa). Patients were questioned on their smoking habits and place of birth and childhood. RESULTS: There were 73 patients with duodenal ulcer, 30 with gastric ulcer, eight with erosive duodenitis, 17 with gastric MALT lymphoma and 54 with non-ulcer dyspepsia. Most (>85%) were seropositive for the heat shock protein B and 26.5-kDa antigens. The prevalence of the other antigens ranged from 45% (VacA) to 68% (urease B). The seroprevalence of CagA antigen was significantly higher (P < 0.01) in cases of gastroduodenal ulcer (84%) than non-ulcer dyspepsia (37%). Similarly, 35-kDa antigen reactivity was more frequent (P < 0.05) in duodenal ulcer patients (75%) than in those with non-ulcer dyspepsia (50%). The antigenic profiles associated with MALT gastric lymphoma and non-ulcer dyspepsia were similar. Multivariate analysis showed that only gastroduodenal ulcer was significantly associated with CagA. Gastroduodenal ulcer and a childhood spent in Africa were both associated with 35-kDa and combined CagA-35-kDa reactivity. CONCLUSIONS: This study confirms the strong seroprevalence of H. pylori CagA antigen and shows a high prevalence of the 35-kDa antigen in patients with gastroduodenal ulcer, especially those raised in Africa. There was no difference in the serological pattern between patients with non-ulcer dyspepsia and those with MALT lymphoma. Tests for antibodies to the CagA-35-kDa antigen combination might be used to select H. pylori-infected dyspeptic patients warranting treatment.

Africa

Omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

OBJECTIVE: In two studies, different regimens of omeprazole-amoxycillin-metronidazole were assessed for the eradication of Helicobacter pylori. DESIGN: Randomized, international, multicentre studies with parallel groups. SETTING: The studies were performed at centres in Canada, Czech Republic, France, Germany, Hungary, Sweden and UK. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients with duodenal ulcer disease (active or in remission) were randomized to 7-day treatment with: omeprazole 40 mg once daily, amoxycillin 500 mg three times daily and metronidazole 400 mg three times daily (OAMtid; n = 242); omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 800 mg twice daily (OAM800; n = 247); or omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 400 mg twice daily (OAM400; n = 127). MAIN OUTCOME MEASURES: Eradication of H. pylori. RESULTS: Intention-to-treat analysis revealed H. pylori eradication rates of 76% (184/242) with OAMtid, 80% (198/247) with OAM800, and 76% (97/127) with OAM400. There was considerable variation in the levels of primary resistance to metronidazole in different countries. The overall eradication rate in patients infected with metronidazole-sensitive H. pylori strains was 85% (313/370), compared with 60% (56/94) in patients harbouring metronidazole-resistant strains (P<0.001). All regimens were generally well tolerated, with mild adverse events occurring in 4-26% of patients (mainly diarrhoea, reversible increase in liver enzymes and headache). CONCLUSION: The OAM combination is effective in curing H. pylori infection. Primary metronidazole resistance may reduce its effectiveness, but an increased daily dosing of metronidazole may partly overcome this problem.

Amoxicillin

Serum antibody responses to Helicobacter pylori and the cagA marker in patients with mucosa-associated lymphoid tissue lymphoma.

The lymphoma of the mucosa-associated lymphoid tissue (MALT) of the stomach has been linked to Helicobacter pylori infection, but the mechanisms involved in B-cell proliferation remain elusive. In a search for putative H. pylori-specific monoclonal immunoglobulin production, an H. pylori strain was isolated from 10 patients with MALT lymphoma and used to detect the specific serum antibody response to the homologous strain by immunoblotting. Moreover, the antigenicity of the different strains was compared by using each of the 10 sera. We found that the different strains induced highly variable patterns of systemic immunoglobulin G antibody response, although several bacterial antigens, such as the 60-kDa urease B, were often recognized by the different sera. The cagA marker was detected in the strains by PCR with specific primers and by dot blot analysis, and the CagA protein was found in the sera of 4 of the 10 patients by immunoblotting. In conclusion, MALT lymphoma patients, like other patients with H. pylori gastritis, exhibit a polymorphic systemic antibody response, despite an apparently similar antigenic profile. The CagA marker of pathogenicity is not associated with this disease.

Antibodies, Bacterial

Co-detection of Helicobacter pylori and of its resistance to clarithromycin by PCR.

Our aim was to develop a rapid molecular test based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and making it possible to detect Helicobacter pylori directly from gastric biopsy samples, and to test its susceptibility to clarithromycin. A 629-bp fragment of the 23S rRNA gene of H. pylori was amplified by PCR and the mutations responsible for clarithromycin resistance were detected with Bsa1 and Bbs1 restriction endonucleases. Thirty-five gastric samples were tested in parallel by standard microbiologic methods (culture and clarithromycin susceptibility testing with E-test strips) and by PCR-RFLP. The 10 culture-negative samples were also PCR-negative. Sixteen out of the 25 culture-positive samples (64%) were PCR-positive. RFLP analysis could be done in 12 cases and the results were in agreement with those of the E-test: susceptibility in five cases, resistance in seven (six A2144G mutations and one A2143G mutation).

Anti-Bacterial Agents

Induction of nitric oxide synthase in vivo and cell injury in rat duodenal epithelium by a water soluble extract of Helicobacter pylori.

1. Helicobacter pylori (Hp) infection, which involves the gastric antrum and duodenal mucosa, may be involved in peptic ulceration by stimulating the local release of cytoxic or pro-inflammatory factors. 2. Nitric oxide (NO) is known to be cytotoxic at high concentration. The aim of the present study was therefore to investigate the ability of a water soluble extract of Hp to induce NO synthase in duodenal mucosa and epithelial cells following its administration in vivo in rats and determine its association with cell damage. 3. Administration of Hp water extract (4 ml kg(-1)) led to the expression of the calcium-independent inducible nitric oxide synthase (iNOS) after 4 h in the duodenum, determined as [14C]-arginine conversion to citrulline. 4. This iNOS activity was not reduced by pretreatment with anti-neutrophil serum (0.4 ml kg(-1), i.p., 3 h before challenge). However, dexamethasone pretreatment (1 mg kg(-1), i.v., 2 h before the extract), or administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1), i.v., 2.5 h after the extract) reduced this activity. 5. Furthermore, iNOS was expressed in duodenal isolated epithelial cells 4 h after the i.v. challenge with the extract, at a time when the cellular viability was also reduced, as assessed by trypan blue exclusion. 6. Dexamethasone pretreatment, administration of L-NAME, or pretreatment with polymyxin B (1 mg kg(-1), i.v.) which binds endotoxin, reduced both the iNOS activity and epithelial cell damage. 7. The induction of NO synthase by the Hp extract thus results in duodenal epithelial cell injury and such actions could play a role in pathogenesis of peptic ulcer disease.

Animals

One-week triple therapy using omeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia: influence of dosage of omeprazole and clarithromycin.

BACKGROUND: Triple therapy based upon omeprazole, amoxycillin and clarithromycin for 7 days is the reference treatment used in France for the eradication of Helicobacter pylori. However, optimal dosages of omeprazole and clarithromycin have not been determined. AIMS: To compare four eradication regimens using this treatment in patients with non-ulcer dyspepsia. METHODS: Two hundred and seventy-four patients with symptoms of dyspepsia, normal upper GI endoscopy and a positive urease test were included in the study. A 13C-urea breath test (UBT) was obtained before and 6 weeks after treatment. Patients were randomized to one of the following 7-day regimens: 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O20AC500) or 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O20AC1000) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O40AC500) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O40AC1000). Compliance was assessed by returned tablet counts. Eradication was defined as conversion from positive 13C-UBT at entry to negative 13C-UBT 6 weeks after cessation of therapy. RESULTS: Two hundred and fifty-eight patients were included in the intention-to-treat (ITT) analysis. From the least to the most effective regimen, eradication rates were: O20AC1000: 60.0% (95% CI: 47.6-72.4), O20AC500: 64.1% (52.3-75.8), O40AC1000: 64.2% (52.7-75.7), O40AC500: 74.6% (64.2-85.0) (N.S.). Overall compliance was good in 92% of patients. The most frequent adverse events were diarrhoea and taste impairment, occurring mainly in the high-dose clarithromycin groups. CONCLUSIONS: Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. This study supports the use of a double dose of omeprazole, although the difference between groups was non-significant, but provides no argument in favour of a high dose of clarithromycin.

Amoxicillin

[Comparison of quantifying Helicobacter pylori gastric infection by culture, histology and C13 urea breath test].

OBJECTIVES: In Helicobacter pylori infection, the bacterial burden may play a role in the pathogenesis of gastric or duodenal ulcerated lesions. It could also influence the results of antimicrobial therapy. No simple test has been validated to quantify Helicobacter pylori density. The aim of this study was to determine the value of histology and/or 13C-urea breath test to quantify the infection as compared with quantitative culture, taken as a reference method. PATIENTS AND METHODS: Biopsies samples were taken from the antrum at endoscopy in 72 patients. Thirty-seven patients with positive urease test at 20 minutes were enrolled in the study. Bacterial density was evaluated from biopsies by quantitative culture and semi-quantitative histological examination (score from 0 to 3). The bacterial density was evaluated as well by 13C-urea breath test from the proportion of 13CO2 in exhaled air (delta 13CO2) at 20, 40, and 60 minutes as compared with the basal level. RESULTS: The bacterial density, evaluated by quantitative culture ranged from 5 CFU to 110,000 CFU per mg of tissue. By histology, a score 1 was found in 5 patients, a score 2 in 17, and a score 3 in 15. delta of 13CO2 measured by 13C-urea breath test ranged from 0.2 to 117.5, from 0.2 to 102, and from 0.6 to 66.7 at 20, 40 and 60 minutes respectively. The quantity of bacteria measured by culture was not significantly higher for these with a score of 3 as compared with those with a pooled score of 1 and 2 (P < 0.05). No significant correlation was found between the results of quantitative culture and these of breath test. CONCLUSION: In practice, evaluation of bacterial burden by a histological score seems only accurate for the most severe density (score 3). The 13C-urea breath test does not allow a reliable quantitative evaluation.

Adult

[Dysphagia revealing Crohn's disease].

Esophageal involvement in Crohn's disease is uncommon. We report here a case with pre-eminent esophageal symptoms and numerous tuberculoid granulomas at histopathological examination. This is an opportunity to review the differential diagnoses and to describe the clinical, endoscopic and histopathological features of this localisation.

Adolescent

Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats.

The time-dependent actions following pretreatment or delayed administration of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on colonic inflammation and inducible NO synthase activity following the intrarectal administration of trinitrobenzene sulphonic acid (TNBS) were evaluated in the rat. Intracolonic instillation of TNBS (30 mg in 0.25 ml of 50% ethanol) led to macroscopic injury, an increase of mucosal myeloperoxidase activity and the expression of the Ca2+-independent inducible NO synthase over 8 days. The inflammatory response following TNBS reached maximum levels between 12 and 72 h and then it declined until 14 days. Oral administration of L-NAME (25 mg/kg per 24 h in the drinking water) 2 days before TNBS augmented macroscopic damage and increased colonic inducible NO synthase activity 6, 12, 24 and 72 h after TNBS administration. In contrast, when L-NAME was administered 6 h after TNBS instillation, at time of expression of inducible NO synthase, the macroscopic lesions were reduced, as well as the enhanced inducible NO synthase activity, determined, over 72 h. Delayed (6 h after TNBS) administration of L-NAME also attenuated the colonic myeloperoxidase activity provoked by TNBS, after 24 h. This activity was not affected by pretreatment (2 days before TNBS) with L-NAME. These findings indicate that the timing of administration of non-selective NO synthase inhibitors such as L-NAME, in models of colitis is critical to the eventual outcome. Thus, pretreatment with L-NAME, which will inhibit constitutive NO synthase, exacerbates the subsequent damage following challenge. In contrast, delayed administration of L-NAME at the time of inducible NO synthase expression, has a beneficial action on the colonic injury and inflammation.

Animals

Endoscopic ultrasonography for the initial staging and follow-up in patients with low-grade gastric lymphoma of mucosa-associated lymphoid tissue treated medically.

BACKGROUND: Endoscopic ultrasonography is an appropriate procedure to assess the depth of tumoral infiltration in primary gastric lymphoma. The aims of the present study were to characterize the endoscopic ultrasonographic aspects of low-grade gastric lymphoma of mucosa-associated lymphoid tissue and to determine the value of this procedure in medical treatment assessment. METHODS: Between 1991 and 1996, 15 patients with low-grade gastric lymphoma of mucosa-associated lymphoid tissue were treated with oral cyclophosphamide and/or anti-Helicobacter pylori treatment. Endoscopic ultrasonography was carried out at the time of the diagnosis in all patients, 8 of whom (4 in complete remission and 4 with a stable or progressive disease) had at least one endoscopic ultrasonography examination within the treatment period (median follow-up 17 months). RESULTS: The initial procedure showed an increased gastric wall thickness from 6 to 12 mm in 8 patients, equal to 5 mm in 5 patients, and normal in 2 patients. The thickening was predominantly of the mucosa alone and/or the submucosa but never extended beyond the muscularis propria. No lymph node was found. Gastric wall thickness returned to normal in the 4 patients in complete remission and remained thick in 3 of the 4 patients with a stable or progressive disease. Of these 3 patients, at least one set of biopsy samples, carried out during follow-up, showed the absence of lymphoma, but histology performed subsequently found evidence of disease. CONCLUSIONS: Endoscopic ultrasonography differentiates superficial from infiltrative types of gastric lymphoma of mucosa-associated lymphoid tissue, which may have a prognostic significance and confirms remission or persistence of the disease with medical treatment during follow-up. When the gastric wall remains thick, even if histology is negative, repeated biopsies should be performed to detect evolving disease or relapse.

Adult