Peptic ulcer disease: one in five is related to neither Helicobacter pylori nor aspirin/NSAID intake.

BACKGROUND: The proportion (and even the reality) of peptic ulcer disease (PUD) not related to H. pylori or NSAID/aspirin is debated. AIM: To analyse the current epidemiological and clinical characteristics of peptic ulcer disease in French general hospitals. METHODS: Prospective multicentre study of patients with peptic ulcer disease in 32 French general hospitals over 1 year. H. pylori status was assessed by histology, and/or serology and/or C13-urea breath test. NSAID/aspirin intake (obtained by direct interview) and data about concomitant diseases were collected on the day of endoscopy. RESULTS: Nine hundred and thirty-three patients were selected during the year 2009. After exclusion of 118 patients with only erosive duodenitis, 24 with major missing data, 13 with other causes of ulcer and 65 negative for H. pylori by only one test, 713 patients were classified into four groups: 285 (40.0%) had only H. pylori infection; 133 (18.7%) only gastrotoxic drugs; 141 (19.8%) had both and 154 (21.6%) neither H. pylori infection nor gastrotoxic drug intake ('idiopathic ulcers'). Patients with idiopathic ulcers differed in many ways both from H. pylori and NSAID/aspirin groups. However, multivariate analysis identified only three independent predictors: age, French metropolitan origin and the presence of comorbidities. CONCLUSION: In a general hospital-based population in France, peptic ulcer disease appears idiopathic in a fifth of cases.

Second-line treatment for failure to eradicate Helicobacter pylori: a randomized trial comparing four treatment strategies.

AIM: To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed. METHODS: In this study named StratHegy patients (n=287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility. The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14). In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14. The 13C-urea breath test was performed before randomization and 4-5 weeks after eradication therapy. RESULTS: In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P<0.01 when compared with OAC7 and OAC14). In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains. CONCLUSIONS: Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing. If susceptibility testing is not available, OAM14 is an appropriate alternative.

False-positive somatostatin receptor scintigraphy due to an accessory spleen.

A patient with previous left caudal pancreatectomy and splenectomy presented with Zollinger-Ellison syndrome. Abdominal CT and endoscopic ultrasonography revealed a mass in the splenic area. Somatostatin receptor scintigraphy showed a nodular increase of the uptake corresponding to the lesion detected with conventional imaging. A second laparotomy was performed and the mass was resected. Histological analysis showed that the nodular lesion was an accessory spleen. Since physiologic uptake of 111In-pentetreotide is seen in the spleen, an accessory spleen mimicking a tumor, specially after previous splenectomy, may result in false-positive somatostatin receptor scintigraphy.

[Treatment of a hemorrhagic duodenal varice by endoscopic sclerotherapy]. / Traitement par sclérothérapie endoscopique d'une varice duodénale hémorragique.

We report the case of a duodenal varix rupture in a 37-year-old man revealing an alcoholic cirrhosis. Endoscopic diagnosis of this duodenal varix was difficult because of its atypical and changing appearance. Endoscopic sclerotherapy was completely successful and there was no recurrent bleeding. Although duodenal varix is rare, this case and the literature emphasize the importance of considering this diagnosis in all patients with duodenal tumoral lesions and suspected portal hypertension. In this context, duodenal biopsy can be dangerous and should be avoided. In case of duodenal varix rupture, endoscopic sclerotherapy appears to be a safe and efficient first-choice therapy.

Helicobacter pylori infection: physiopathologic implication of N alpha-methyl histamine.

BACKGROUND/AIMS: In the gastric mucosa of Helicobacter pylori-infected subjects, we previously detected N alpha-methyl histamine (N alpha-MeHA), a minor catabolite of histamine and a potent agonist of histamine H3 receptors. The origin of N alpha-MeHA and its effects on gastric histamine and somatostatin in infected subjects were investigated. METHODS: Ten noninfected patients and 13 patients with intense colonization were compared. N alpha-MeHA content and its synthetic enzyme activity, N alpha-histamine methyltransferase, binding of [3H]N alpha-MeHA, histamine and somatostatin contents, and histidine decarboxylase activity were assayed in antral and fundic biopsy specimens and in cultured H. pylori strains. RESULTS: Gastric histamine and somatostatin contents as well as histidine decarboxylase activity were decreased in infected patients and were restored to normal after antimicrobial treatment. Both N alpha-MeHA and N alpha-histamine methyltransferase activity were present in the mucosa of infected patients and in cultured strains and were very low in noninfected patients or after eradication of H. pylori. [3H]N alpha-MeHA bound to gastric mucosa but not to cultured strains. The [3H]N alpha-MeHA specific binding sites were characterized as H3 receptors. The amount of bound [3H]N alpha-MeHA seemed correlated positively with somatostatin content and histidine decarboxylase activity and negatively with N alpha-MeHA content and N alpha-histamine methyltransferase activity. CONCLUSIONS: H. pylori is the main source of gastric N alpha-MeHA that may lower histidine decarboxylase activity and somatostatin content through H3 receptors.

Argyrophil cells, mast cells, and histamine in the fundic mucosa of antrectomized patients.

Fasting gastrinemia, fundic argyrophil cell density, mast cell number, basal fundic histamine content and histidine decarboxylase activity were determined in 20 antrectomized patients and 20 control subjects. Fasting gastrinemia and fundic argyrophil cell density were significantly lower in antrectomized patients than in controls, whereas fundic mast cell number, basal histamine content, and histidine decarboxylase activity did not differ significantly between the two groups. In antrectomized patients the basal fundic histamine content appears related to the fundic mast cell number, as a consequence of the reduced effect of gastrin on argyrophil cells.

Seven years of recurrent severe strongyloidiasis in an HTLV-I-infected man who developed adult T-cell leukaemia.

OBJECTIVE: Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is endemic in Japan, the Caribbean basin and Africa, where it has been aetiologically linked to certain chronic myelopathies and adult T-cell leukamia (ATL). We sought to investigate whether strongyloidiasis, a parasitic disease common in these areas, might be a cofactor in the pathogenesis of ATL, as some reports have suggested. PATIENTS, PARTICIPANTS: One 35-year-old HTLV-I-seropositive French West Indian man with a 7-year history of recurrent strongyloidiasis associated with episodic hyperinfestation presenting at the Centre Hospitalier Intercommunal, Villeneuve St Georges, France. INTERVENTIONS: Treatment with various chemotherapeutic agents and symptomatic therapy for hypercalcaemia and antiviral therapy (zidovudine and interferon). RESULTS: The patient developed ATL and died shortly after, despite chemotherapy. Immunological and virological studies performed during the last 15 months of his life showed an increase of the percentage of peripheral ATL cells, and progression from a polyclonal to a monoclonal integration of HTLV-I proviral DNA in the peripheral blood mononuclear and lymph-node cells. CONCLUSIONS: Recurrent strongyloidiasis appears to have been a possible cofactor associated with progression from healthy carrier state to ATL in our patient.

Arthritis associated with Strongyloides stercoralis.

A case of reactive arthritis combined with uveitis associated with a longstanding and heavy infestation with Strongyloides stercoralis is reported in a 32-year-old HTLV-1 positive West Indian man. Stool examination revealed numerous adult worms and larvae. Treatment with thiabendazole and ivermectin resulted in prompt improvement.

Increased adhesion to fibronectin and Mo-1 expression by diabetic monocytes.

As excessive monocyte adhesion to blood vessel wall could produce endothelial cell injury, we undertook comparative studies on the monocyte adhesiveness in insulin-dependent diabetics with vascular complications (n = 26) and healthy, normal subjects (n = 36). In the diabetic group, the extent of monocyte adhesion on fibronectin- and autologous plasma-coated surfaces was significantly increased compared with that in the control group (p less than 0.01 on both types of surfaces). Monocytes adhesion to the plasma-coated surface, but not to the fibronectin-coated surface, could be inhibited by monoclonal anti-Mo-1 antibody in a dose-dependent manner. For diabetic monocyte adhesion, a higher amount of anti-Mo-1 antibody was required to produce a similar extent of inhibition as observed with control monocytes. This indication of increased Mo-1 expression on diabetic monocytes was further confirmed by analyzing the fluorescence intensity of monocytes labeled with the antibody anti-Mo-1. The results of the present study suggest that diabetic monocytes have increased adhesiveness as the result of increased expression of fibronectin and Mo-1 receptors.

Increased procoagulant response of monocytes from patients with familial Mediterranean fever.

Familial Mediterranean Fever (FMF) is an inherited disease of unknown etiology characterized by recurrent inflammatory episodes. Circulating fibrin was found in patients with FMF in absence of clinical manifestation of thrombosis and was statistically less frequently observed in patients treated with colchicine. These results suggest a cellular dysfunction. Therefore, we examined the procoagulant activity (PCA) of isolated mononuclear leukocytes and purified monocytes from FMF patients (n = 20). No PCA was detectable on freshly-isolated monocytes. After several hours of culture. FMF monocytes contained more PCA than control cells and the difference was more marked after endotoxin stimulation. Data obtained with coagulation factor-deficient plasma and anti-human apoprotein III antiserum indicated that the enhanced PCA in FMF monocytes is thromboplastin-like. Lysozyme and interleukin 1 production by monocytes were similar in patients and controls. The increased monocyte PCA appears to be due to an intrinsic and selective higher responsiveness of monocytes.

Histamine H2 receptor activity and histamine metabolism in human U-937 monocyte-like cells and human peripheral monocytes.

Functional and specific histamine H2 receptors were characterized in human peripheral monocytes and in U-937 cells, before and after retinoic acid--induced differentiation into monocyte/macrophage-like cells. The relative potencies of histamine and the H1, H2 receptor agonists and antagonists studied are remarkably similar in U-937 cells and U-937 monocytes. There is no change in histamine concentration and activity of the enzymes forming and degrading histamine during monocytic-like differentiation. The results raise the possibility that histamine H2 receptors might be involved in pathophysiological regulations (proliferation/differentiation and biological function) of normal and leukemic monocytes.

[Therapeutic prospects and prostaglandins in vascular pathology]. / Perspectives thérapeutiques et prostaglandines en pathologie vasculaire.

The discovery of thromboxanes and prostacycline has opened up a new therapeutic approach to vascular and thrombotic diseases. Aspirin is no longer considered to be an antiaggregant drug, but an inhibitor of cyclooxygenase which, depending on the dose, may have an effect on platelets and the vessel. Thromboxane synthetase inhibitors and thromboxane receptor blockers represent a new mode of inhibition of platelet activation. Therapeutic trials of the vasodilator and antiaggregant prostacycline have been carried out in obliterative arterial disease and Raynaud' syndrome with a certain degree of success. The production of a stable analogue of prostacycline and the manipulation of the leukotrienes are the therapeutic hopes for the future.