Implications of oral Helicobacter pylori for the outcome of its gastric eradication therapy

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) is an important pathogen in gastritis, peptic ulcer and possibly gastric cancer, but several questions remain unanswered. Particularly how the organism is transmitted and what is the relationship between oral presence of H. pylori and the gastric infection. Accordingly, we aimed to characterize the H. pylori in oral cavity and to evaluate its relationship to gastric H. pylori infection. MATERIALS AND METHODS: Out of total 100 screened for H. pylori infection female subjects (40 to 85 y), 49 patients (pts), who had positive C-urea breath test (UBT) and dyspeptic symptoms, agreed for 1 week regimen of triple anti-H. pylori therapy. The presence of H. pylori in oral cavity was assessed using bacterial culture from saliva and gingival pockets. Gastric H. pylori infection was estimated using capsulated C-urea breath test and plasma anti-H. pylori IgG and saliva IgA antibodies. In addition, plasma gastrin, ghrelin, and pepsinogen I were measured by radioimmunoassay. In selected patients, gastroscopy was additionally performed and gastric biopsy samples were taken for H. pylori random amplification of polymorphic DNA genetic profiling. RESULTS: The triple therapy resulted in gastric H. pylori eradication in 79% pts, along with significant decrease of plasma gastrin combined with an increase in plasma ghrelin and pepsinogen I (PgI) levels and a marked alleviation of dyspeptic symptoms. In contrast to gastric effects, the eradication therapy failed to cause any changes in the presence of H. pylori in oral cavity. Moreover no relationship was observed between the presence of H. pylori in oral cavity and the gastric H. pylori eradication. In line with these findings, no relationship between gastric and oral H. pylori was found using genetic profiling by random amplification of polymorphic DNA. CONCLUSIONS: H. pylori was detected both in the oral cavity and the stomach but oral H. pylori had no relation to gastric H. pylori and remained unaffected by eradication of gastric H. pylori.     

Chronic haloperidol and clozapine administration increases the number of cortical NMDA receptors in rats

The aim of the present study was to examine the influence of 3-month administration of haloperidol (1 mg/kg per day) and clozapine (30 mg/kg per day) in drinking water on cortical NMDA (N-methyl-d-aspartate) receptors in rats. On day 5 of withdrawal, the animals were killed and their brains were removed. The binding of [³H]MK-801 ([³H](5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine) and [³H]CGP 39653 ([³H]d,l-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) to NMDA receptors in different cortical areas, as well as the binding of [³H]spiperone to dopamine D₂ receptors in the striatum, were analysed by quantitative autoradiography. Haloperidol increased the binding of [³H]CGP 39653 in frontal, insular and parietal cortices. Clozapine increased the binding of [³H]CGP 39653 in insular and parietal cortices. Haloperidol, but not clozapine, increased the binding of [³H]spiperone in the striatum. None of the neuroleptics influenced the binding of [³H]MK-801 to cortical NMDA receptors. An additional assay revealed an increase in the B _max value, with no significant changes in the K _D of [³H]CGP 39653 binding in parieto-insular cortical homo-genates as a result of haloperidol and clozapine administration. The present results suggest that long-term treatments with haloperidol and clozapine increase the number of NMDA receptors in different cortical regions. Received: 15 September 1998 / Accepted: 25 January 1999     

Biomarkers in Various Types of Atrophic Gastritis and Their Diagnostic Usefulness

Atrophic gastritis has been shown to involve either the oxyntic gland area, resulting in hypergastrinemia and hypopepsinogenemia I, the antral gland area, causing hypogastrinemia without change in serum pepsinogen I (diffuse antral gastritis; DAG), or the entire gastric mucosa (multifocal atrophic gastritis; MAG), resulting in both hypogastrinemia and hypopepsinogenemia I; and rare atrophic gastritis limited to the oxyntic gland area, with antibodies against oxyntic cells and/or intrinsic factor (autoimmune metaplastic atrophic gastritis; AMAG). This study was performed on 126 patients with various forms of gastritis and on 126 age- and gender-matched controls, who were subjected to endoscopy with biopsy, H. pylori testing (¹³C-UBT, serology), assays for serum gastrin and pepsinogen I, and testing for basal and pentagastrin-induced gastric acid secretion. The following groups of patients were examined: group I (N = 22), with AMAG; group II (N = 53), with DAG; group III (N = 51), with MAG; and group IV (N = 126), age- and gender-matched controls without gastritis. The following changes were found. In group I very high serum gastrin and very low pepsinogen I were observed, and all patients were achlorhydric and H. pylori negative. In group II, with low serum gastrin and normal pepsinogenemia and gastric chlorhydria, all patients were H. pylori positive. In group III, with lower serum gastrin and lower pepsinogen I levels and reduced chlorhydria, all patients were also H. pylori positive. And all group IV controls, with normal serum gastrin and pepsinogen I and normal gastric acid secretion without antral or fundic gastritis, were H. pylori negative. We conclude that measurements of serum gastrin and pepsinogen I and gastric acid secretion as well as testing for H. pylori infection may be useful in noninvasive diagnosis of various types of atrophic gastritis and in identification of patients with premalignant gastritis and a high risk of gastric cancerogenesis.     

Effect of Peginterferon or Ribavirin Dosing on Efficacy of Therapy With Telaprevir in Treatment-Experienced Patients With Chronic Hepatitis C and Advanced Liver Fibrosis: A Multicenter Cohort Study

We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm³ or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm³) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.     

The role of self-monitoring of blood glucose in glucagon-like peptide-1-based treatment approaches: a European expert recommendation

The role of glucagon-like peptide (GLP)-1-based treatment approaches for type 2 diabetes mellitus (T2DM) is increasing. Although self-monitoring of blood glucose (SMBG) has been performed in numerous studies on GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, the potential role of SMBG in GLP-1-based treatment strategies has not been elaborated. The expert recommendation suggests individualized SMBG strategies in GLP-1-based treatment approaches and suggests simple and clinically applicable SMBG schemes. Potential benefits of SMBG in GLP-1-based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and diabetes education. Its length and frequency should depend on the clinical setting and the quality of metabolic control. It is considered to play an important role for the optimization of diabetes management in T2DM patients treated with GLP-1-based approaches.     

ACE gene I/D polymorphism and the presence of renal failure or hypertension in autosomal dominant polycystic kidney disease (ADPKD)

Sir, Epidemiological data have suggested that interactions betweenmultiple genetic and environmental factors are involved in theprocess of progressive renal damage in the course of variouskidney diseases, including autosomal polycystic kidney disease[1–4     

(S)-4C3HPG, a mixed group I mGlu receptor antagonist and a group II agonist, administered intrastriatally, counteracts parkinsonian-like muscle rigidity in rats

The aim of the present study was to determine whether S-4-carboxy-3-hydroxyphenylglycine (S)-4C3HPG, a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, attenuated parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano and electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat’s hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). (S)-4C3HPG injected in doses of 5 and 15 μg/0.5 μl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). The present results suggest that blockade of mGluR1 receptors and/or activation of mGluR2 ones, localized in the rostral part of the striatum, may be responsible for the anti-parkinsonian effect of (S)-4C3HPG.     

Prevalence and prediction of renal artery stenosis in patients with coronary and supraaortic artery atherosclerotic disease.

BACKGROUND: Renal atherosclerosis is associated with increased cardiovascular mortality. This study aimed to determine the prevalence and predictors of renal artery stenosis (RAS) in patients with coronary artery disease (CAD) and supraaortic arteries (SA) stenosis. METHODS: Renal angiography was performed in 1193 (807 men) consecutive patients referred for coronary or SA angiography. Group I included 296 (136 men, 60.1 +/- 9.5 years) patients with no significant (< 50%) lesion in coronary arteries or SA; group II included 706 (526 men, 62.2 +/- 9.7 years) patients with stenosis > or = 50% within single arterial territory (coronary arteries or SA) and group III included 191 (145 men, 64.9 +/- 8.5 years) patients with stenosis > or = 50% in both territories. RESULTS: Some RAS was found in 55 (18.6%) patients in group I, 250 (35.4%) patients in group II and 115 (60.2%) patients in group III (P < 0.001). The proportion of patients with RAS > or = 50% in groups I, II and III was 3.3, 6.2 and 18.3%, respectively (P < 0.001). RAS prevalence increased with the number of stenosed coronary arteries (38.4% in 1-vessel, 42.1% in 2-vessel, 48.5% in 3-vessel CAD, P < 0.001). Independent predictors of RAS > or = 50% identified by logistic regression analysis were SA stenosis [relative risk (RR) = 3.28, P < 0.001], 2-3-vessel-CAD (RR = 2.04, P = 0.002), creatinine level > or = 1.07 mg/dl (RR = 2.95, P < 0.001), hypertension (RR = 2.97, P = 0.012) and body mass index < 25 kg/m(2) (RR = 1.42, P = 0.169). A calculated score for RAS > or = 50% prediction (based on the regression model) was reliable (coefficient of determination, R = 0.978) and showed a sensitivity of 77.5% and a specificity of 63.9%. CONCLUSIONS: RAS prevalence and severity increases with the number of arterial territories involved and CAD severity. The following independent predictors of RAS > or = 50% were identified: SA involvement, 2-3-vessel-CAD, serum creatinine level and hypertension.