Multicenter survey of routine determinations of resistance of Helicobacter pylori to antimicrobials over the last 20 years (1990 to 2009) in Belgium.

We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.

Marching cohort of Helicobacter pylori infection over two decades (1988-2007): combined effects of secular trend and population migration.

The prevalence of Helicobacter pylori infection is decreasing in developed countries. In this study we included 22,612 patients in whom a first culture of gastric biopsy (routinely performed in our medical centres) yielded an interpretable result over a 20-year period (1988-2007) in Brussels. The effects of patients' age, gender and ethnic background were analysed. The overall proportion of H. pylori-infected patients was 37·7%, with a progressive decline over time (P<10(-5)). A gender effect was observed in adults. The lowest infection rate was observed in Western European patients (n=11,238) with respectively 36·2% and 15·2% infected subjects in 1988 and 2007, compared to 71·7% and 40% in North African patients (n=3200) (P<10(-5)). However, no trend of decline was observed over time in North African children aged ≤9 years. These data show the effects of time, age and ethnicity on the prevalence of H. pylori infection, and its complex heterogeneity in the same cosmopolitan urban area.

A plasma membrane Ca2+ ATPase isoform at the postsynaptic density.

Most excitatory input in the hippocampus impinges on dendritic spines. Entry of Ca(2+) into spines through NMDA receptors can trigger a sequence of biochemical reactions leading to sustained changes in synaptic efficacy. To provide specificity, dendritic spines restrict the diffusion of Ca(2+) signaling and downstream molecules. The postsynaptic density (PSD) (the most prominent subdomain within the spine) is the site of Ca(2+) entry through NMDA receptors. We here demonstrate that Ca(2+) can also be removed via pumps embedded in the PSD. Using light- and electron-microscopic immunohistochemistry, we find that PMCA2w, a member of the plasma membrane Ca(2+)-ATPase (PMCA) family, concentrates at the PSD of most hippocampal spines. We propose that PMCA2w may be recruited into supramolecular complexes at the postsynaptic density, thus helping to regulate Ca(2+) nanodomains at subsynaptic sites. Taken together, these results suggest a novel function for PMCAs as modulators of Ca(2+) signaling at the synapse.

Atypical symptoms of GORD in Belgium: epidemiological features, current management and open label treatment with 40 mg esomeprazole for one month.

UNLABELLED: Frequency of atypical symptoms in patients suffering from gastro-oesophageal reflux disease (GORD) is not well known, and the optimal management of such symptoms has not been well established. Our aims were to set up an observatory of these atypical symptoms of GORD in Belgium and to study the efficacy of one month treatment with esomeprazole 40 mg. PATIENTS AND METHODS: Gastroenterologists participating in this observational survey were asked to register every new outpatient with symptoms of GORD during a period of 20 consecutive working days. All patients who reported predominant presence of atypical manifestations of GORD were documented and characterized more in detail. In patients with dominant chest pain or ENT symptoms, a treatment with esomeprazole 40 mg daily during 4 weeks was proposed. RESULTS: 90 gastroenterologists included 2864 patients consulting for symptoms suggestive of GORD, including 776 (27.1%) with dominant atypical symptoms. Endoscopy (performed in 2800 patients) showed significantly less oesophagitis in atypical than in typical GORD patients (68% vs. 81.1%; P < 0.0001). Management of atypical GORD patients appeared to be very heterogeneous. Overall 516/776 patients were included in the open phase of treatment with esomeprazole 40 mg, but data for analysis are only available in 228 patients. After one month, symptoms had disappeared in 57.1% and significantly improved in 26.6%. CONCLUSION: Atypical GORD represents a large number of consultations in gastroenterology in Belgium. It is associated with less endoscopic lesions than typical GORD. Its management is heterogeneous reflecting the lack of guidelines on this topic. Response rate after esomeprazole 40 mg for one month in this open uncontrolled trial was high. This result warrants confirmation in a placebo-controlled trial.

Observational survey of NSAID-related upper gastro-intestinal adverse events in Belgium.

OBJECTIVES: To evaluate the impact of NSAID use on current routine upper GI endoscopy (UGIE) and to compare the lesions found in NSAID users and non-users. METHODS: Participating gastroenterologists consecutively documented outpatients with and without suspicion of bleeding, referred for upper gastrointestinal endoscopy. Patient characteristics, presence of risk factors, NSAID use and endoscopic findings were reported on standard data collection forms. MAIN RESULTS: A total of 2685 non-bleeding and 159 bleeding patients were enrolled within a time period of 2 months. NSAID therapy was present in 20% of the non-bleeding patients and at least 9% of referrals for endoscopy were directly related to suspected NSAID adverse events. Nearly half of acute bleeding patients (42%) were NSAID users, including aspirin for cardioprevention. Warning digestive symptoms prior to acute bleeding were frequently absent (56%). Oesophagitis was the main endoscopic diagnosis (51% of patients). Gastroduodenal (GD) ulcer was significantly more frequent in NSAID users, whereas oesophagitis and bleeding oesophageal varices were more frequent among non-users. Analysis of odds ratio's demonstrated NSAID use to significantly increase the risk for gastric ulcer in the whole patient group (OR = 2.73; 95% confidence interval (CI): 1.98-3.77; p < 0.001) and, in addition, for duodenal ulcer in the elderly (> 65 y) subgroup (OR = 2.91; 95% CI: 1.52-5.59; p < 0.05). CONCLUSIONS: This survey confirms the high incidence of GD ulcers in NSAID users and the risk for serious gastrointestinal complications, often occurring without warning symptoms. It underlines the impact of NSAID use on the routine endoscopy load, the necessity of careful selection of patients for NSAID prescriptions and the need for gastropreventive measures, particularly in elderly patients and patients associating multiple risk factors.

Substance P and nitric oxide signaling in cerebral cortex: anatomical evidence for reciprocal signaling between two classes of interneurons.

Parvalbumin-containing fast-spiking interneurons in the cerebral cortex exhibit widespread electrical coupling, as do somatostatin-containing low-threshold spiking interneurons. Besides the classical neurotransmitter gamma-aminobutyric acid, these cortical interneurons may also release various neuropeptides including substance P (SP), as well as the freely diffusible messenger nitric oxide (NO). To investigate whether these two networks of interneurons might interact via these nonclassical messengers, we performed immunocytochemistry for SP and NO signaling pathways in rat somatic sensory cortex. SP was found in a subset of parvalbumin-positive cells concentrated in layers IV and V, whereas its receptor, NK1, was found in a subset of somatostatin-containing neurons (and also, at much lower levels, in a disjoint subset of parvalbumin-containing neurons). Only 4% of SP-containing axon terminals were apposed to NK1-positive dendrites, suggesting that in the cerebral cortex, SP may act predominantly as a paracrine neuromediator. Nitric oxide synthase-I (NOS-I), the synthetic enzyme for NO, was found almost exclusively in NK1-positive neurons; 95% of intensely somatostatin/NK1-positive neurons were also positive for NOS-I, and 94% of NOS-positive neurons were also positive for NK1. Immunoreactivity for soluble guanylyl cyclase (the NO receptor) was at high levels in the apical dendrites of layer V pyramidal neurons and in parvalbumin/SP-positive neurons. These data point to a novel reciprocal chemical interaction between two inhibitory networks in the rat neocortex.

A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2.

The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta(2) adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.

Immunohistochemical localization of nitric oxide synthase and soluble guanylyl cyclase in the ventral cochlear nucleus of the rat.

The diffusible messenger nitric oxide (NO) is implicated in auditory processing. It acts in the brain largely through activation of soluble guanylyl cyclase (sGC), a heterodimer comprised of alpha and beta subunits. The authors used immunohistochemistry to study the NO/guanosine 3',5'-cyclic monophosphate (cGMP) pathway in the cochlear nucleus of Sprague-Dawley rats. Central fibers of the cochlear nerve were stained for neuronal nitric oxide synthase (NOS-I) but not for sGCbeta. Within the ventral cochlear nucleus, a large fraction of principal cells were immunopositive for both NOS-I and sGCbeta; these cells could be seen at times receiving contacts from NOS-I-positive fibers. sGC staining of somatic cytoplasm extended into the distal dendritic tree. At variance with this pattern, NOS-I was concentrated mainly in somata. Double-labeling experiments showed that most of the principal neurons expressed both antigens. By contrast, in the granule cell domain, small cells that were immunopositive for NOS-I rarely corresponded to those that were immunopositive for sGC. To assess whether NOS-I and sGC immunoreactivities colocalize with their respective catalytic activities, the authors performed multiple labeling with L-citrulline (a by-product of the formation of NO from L-arginine) and cGMP, respectively. L-citrulline was restricted to NOS-I-positive elements, and the large majority of NOS-expressing neurons were positive for citrulline. Multiple labeling revealed that almost all sGC-positive neurons also accumulated cGMP both in the ventral cochlear nucleus and in the granule cell domain. These data suggest that NO is a signaling molecule in the cochlear nucleus, perhaps functioning in both a paracrine manner and an autocrine manner.

Differential cellular and subcellular localization of ampa receptor-binding protein and glutamate receptor-interacting protein.

Excitatory synaptic currents in the mammalian brain are typically mediated by the neurotransmitter glutamate, acting at AMPA receptors. We used immunocytochemistry to investigate the distribution of AMPA receptor-binding protein (ABP) in the cerebral neocortex. ABP was most prominent in pyramidal neurons, although it was also present (at lower levels) in interneurons. ABP and its putative binding partners, the GluR2/3 subunits of the AMPA receptor, exhibited prominent cellular colocalization. Under appropriate processing conditions, colocalization could also be documented in puncta, many of which could be recognized as dendritic spines. However, a sizable minority of GluR2/3-positive puncta were immunonegative for ABP. Because glutamate receptor-interacting protein (GRIP) may also anchor GluR2, we studied the relative distribution of ABP and GRIP. There was extensive colocalization of these two antigens at the cellular level, although GRIP, unlike ABP, was strongest in nonpyramidal neurons. Different parts of a single dendrite could stain selectively for ABP or GRIP. To further characterize this heterogeneity, we investigated punctate staining of neuropil using synaptophysin and the membrane tracer DiA to identify probable synapses. Some puncta were comparably positive for both ABP and GRIP, but the majority were strongly positive for one antigen and only weakly positive or immunonegative for the other. This heterogeneity could be seen even within adjacent spines of a single dendrite. These data suggest that ABP may act as a scaffold for AMPA receptors either in concert with or independently from GRIP.

SAP97 concentrates at the postsynaptic density in cerebral cortex.

SAP97, a PDZ-containing protein, is reported to concentrate in axon terminals, where its function remains unknown. Using highly specific new antibodies, we show that SAP97 in rat cerebral cortex is associated with heteromeric AMPA receptors via a selective biochemical interaction between SAP97 and the GluR1 subunit. Using light and electron microscopic immunocytochemistry, we demonstrate cellular and synaptic colocalization of SAP97 and GluR1, and show that SAP97 concentrates at synapses that contain GluR1 but not necessarily GluR2 or GluR3. Using quantitative postembedding immunogold electron microscopy, we find that SAP97 is at highest concentration within the postsynaptic density of asymmetric synapses. These data suggest that SAP97 may help to anchor GluR1-containing AMPA receptors at the synapse. As a multifunctional scaffolding protein, SAP97 may organize components of AMPA-related intracellular signalling pathways, including those associated with calcium-permeable homomeric GluR1 channels.

Comparison of tests for assessment of Helicobacter pylori eradication: results of a multi-centre study using centralized facility testing.

BACKGROUND: The accuracy of diagnostic tests to assess Helicobacter pylori eradication has rarely been performed. AIM: To compare the tests most commonly used for this purpose, i.e. histology, culture and (13)C urea breath test performed in centralized facilities. METHODS: Prospective study where patients were included in four centres and diagnostic tests performed centrally by biologists experienced in the field. Gastric biopsies were obtained from antrum and corpus (two for histology, two for culture from each site) 4-6 weeks after an eradication treatment. The definition of a gold standard for H. pylori-positive patients was either a positive culture or both positive histology and urea breath test results. RESULTS: Ninety-seven patients for whom data on histology, culture and (13)C urea breath test were available were included. The majority were females (60%) suffering from non-ulcer dyspepsia (52%) and having received proton-pump inhibitor-based triple therapy (62%). Forty-one per cent of the patients were H. pylori-positive according to the gold standard. The sensitivities were 90%, 95% and 92.5% and the specificities 100%, 98.2% and 100% for culture, histology and (13)C urea breath test, respectively. CONCLUSION: All the methods had excellent specificity but the sensitivity ranged between 90 and 95%. The combination of two techniques which increases the sensitivity to virtually 100% is recommended in situations where the eradication treatment requires a precise evaluation such as in clinical trials.

Immunolocalization of mGluR1alpha in specific populations of local circuit neurons in the cerebral cortex.

By coupling glutamate to the IP(3) signaling pathway, group I metabotropic receptors can increase intracellular Ca(2+) concentration, and might thus contribute to excitotoxicity. To identify neurons that might be vulnerable to such injury, we performed immunofluorescence histochemistry for metabotropic glutamate receptor 1alpha (mGluR1alpha) in the cerebral cortex of adult rat. mGluR1alpha was in somata and dendrites of a subset of non-pyramidal neurons scattered throughout the cerebral cortex. To further characterize mGluR1alpha-positive neurons, we investigated its colocalization with several neurochemical markers. Nearly all mGluR1alpha-positive cells were interneurons immunopositive for gamma-aminobutyric acid. The majority (70-80%) of mGluR1alpha-immunopositive neurons were double-labeled for somatostatin. Approximately half of calretinin-positive neurons and 30% of calbindin-positive neurons expressed mGluR1alpha. In contrast, parvalbumin-expressing neurons were rarely positive for mGluR1alpha. Neurons staining strongly for mGluR1alpha were also positive for GluR1. These results indicated that mGluR1alpha is expressed by specific classes of GABAergic neurons in the neocortex, and suggests a mechanism by which these neurons may be especially vulnerable to excitotoxic injury.

Characterization of glutamate receptor interacting protein-immunopositive neurons in cerebellum and cerebral cortex of the albino rat.

Glutamate receptor interacting protein (GRIP) binds to the C-terminus of the glutamate receptor 2 (GluR2) subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in vitro and may play an important role in the synaptic organization of these receptors. To determine the distribution of GRIP in vivo, GRIP was localized immunocytochemically in cerebellum and cerebral cortex of adult Sprague-Dawley rats. In the cerebellar cortex, GRIP staining was prominent in perikarya and proximal dendrites of Purkinje cells, whereas Golgi cells were stained more weakly. Double labeling revealed that GRIP and GluR2 were colocalized in Purkinje cells but not in Golgi cells. In the cerebral cortex, GRIP-stained dendrites and somata of nonpyramidal neurons were scattered throughout cortical layers, whereas pyramidal cells were only weakly immunopositive. GRIP was especially prominent in a subset of GluR2-containing cells that also expressed a high level of GluR1. The large majority of strongly GRIP-positive cells in neocortex were immunopositive for gamma-aminobutyric acid (GABA), including the overwhelming majority of calbindin-positive cells in superficial cortical layers, most of the parvalbumin-positive cells, and half of the calretinin-positive interneurons. Staining in the neuropil became more punctate after antigen was unmasked with proteinase K. Electron microscopic localization in the cerebral cortex by postembedding immunogold showed that somatic GRIP was associated with rough endoplasmic reticulum and Golgi apparatus. GRIP was seen over the postsynaptic density of axospinous and axodendritic asymmetric synapses and at high levels in dendrites of GABA-positive neurons. The present data support a role for GRIP in anchoring AMPA receptors and suggest that GRIP trafficking may be especially active in GABAergic neurons.

Expression of NR2 receptor subunit in rat somatic sensory cortex: synaptic distribution and colocalization with NR1 and PSD-95.

Functional N-methyl-D-aspartate (NMDA) receptors comprise heteromeric combinations of NR1 and NR2 subunits. In the present study, we employed light and electron microscopic immunocytochemistry to study the expression of NR2A and NR2B (NR2A/B) protein in somatic sensory cortex of adult rats. To relate this distribution to that of NR1 and to the NMDA receptor anchoring protein PSD-95, we documented extensive cellular colocalization of NR2A/B with NR1 at the light microscopic level. In contrast, PSD-95 exhibited little somatic staining, being restricted mainly to dendrites and neuropil. We employed postembedding immunocytochemistry to study the ultrastructural expression of NR2A/B. Labeling in neuronal perikarya was associated with rough endoplasmic reticulum and Golgi apparatus; in dendrites, gold particles labeled microtubules. The preponderance of labeling was associated with asymmetric synapses. Double immunolabeling revealed that NR2 colocalized in many synapses with NR1 and with PSD-95. Quantitative measurements revealed that density of gold particles coding for both NR2 and PSD-95 was highest just inside the postsynaptic membrane. Tangentially along the membrane, gold particles were concentrated at the synaptic specialization. These data provide structural evidence in neocortex for heteromeric NMDA receptors anchored at the postsynaptic membrane.

How (who?) and when to test or retest for H. pylori.

Several direct/invasive and indirect/non-invasive diagnostic tests are available for the diagnosis of H. pylori infection. Invasive tests require biopsy sampling of the gastric mucosa and include rapid urease test, histology, bacterial culture and polymerase chain reaction technique. Non-invasive tests include the urea breath test and serological assays. This review gives a critical comparative analysis of accuracy, advantages and limitations of the different diagnostic tests including current cost and availability in Belgium. Rapid urease testing (RUT) of gastric biopsy specimens is probably the initial test of choice in patients undergoing endoscopy because of its low cost, rapid availability of results, simplicity and accuracy. Histological examination of gastric biopsy samples should be mandatory at the initial presentation of the patient because it also gives insight on the status of the gastric mucosa (inflammation & premalignant changes). Although not mandatory for primary diagnosis, a biopsy for culture and sensitivity testing should always be obtained when it is available and when endoscopy is undertaken as part of the patient's management. Among the non-invasive tests, the place of serology remains questionable for other than epidemiological purposes. How is H. pylori infection best diagnosed? How many tests are needed in routine clinical practice? The answer will depends on the clinical setting and local availability of the tests. For primary diagnosis in dyspeptic patients--where endoscopy is an important tool--a biopsy-based detection system is appropriate an we recommend the use of at least two diagnostic tests based on different principles, like RUT (with 1 or 2 biopsy specimen/test) and histology (including antrum & corpus biopsies) which are widely available. Alternatively a urea breath test may also be recommended when endoscopy is not required. Post-treatment monitoring seems to be justified in most cases and must always be performed at least 4-6 weeks after completion of therapy. The urea breath test is probably the method of choice for non-invasive testing in this clinical setting. When endoscopy is required, multiple biopsy specimens both from the antrum and the corpus and the use of at least two different diagnostic methods must be performed. Whenever possible, culture should always be done as it is very specific and allows testing of antimicrobial susceptibility which is mandatory in case of treatment failures. Neither the "Test and Treat" nor the "Test and Scope" strategies have been investigated in terms of effectiveness of symptoms relief and cost in Belgium and cannot therefore be recommended at this time.

Developmental distribution of astrocytic proteins in the rat cochlear nucleus.

To investigate the developmental distribution of cochlear nucleus (CN) astrocytes, we used immunocytochemical localization of glial fibrillary acidic protein (GFAP) and S100beta in rats at 0, 5, 10, 15, 21, 30 postnatal days plus the adult. Differential developmental trends were observed for both proteins. The spatial distribution showed a progressive increase of the number of GFAP-immunoreactive (GFAP-IR) astrocytes during development. GFAP positive cells occurred first in the granule cell domain of the ventral CN and in the molecular cell layer of the dorsal CN, then followed an outside to inside pattern of progression. The GFAP-IR reached an adult distribution 1 month after birth. By contrast with GFAP, the apparition of S100beta-immunoreactivity (S100beta-IR) was abrupt (between 0 and 5 days) followed by a rapid stabilization of density and distribution of IR cells (between 15 and 21 days). The developmental distribution of S100beta-IR cells occurred from the posterodorsal region and progressed toward a rostroventral direction. With contrast to GFAP-IR astrocytes, S100beta-positive cells were mainly restricted to the central part of the CN, while only few IR astrocytes were observed in the granule cell domain of the ventral CN or in the molecular cell layer of the dorsal CN. This differential distribution suggests that both antigens were expressed by two different cell populations at least, it is obvious during the first postnatal week. The gradual expression of GFAP and S100beta is interpreted as reflecting the time course of astrocytic maturation. These data suggest that the maturation of CN astrocytes may be linked to the final maturation of CN neurons.

Localization of neurotrophin-3-like immunoreactivity in the rat cochlear nucleus.

Immunohistochemistry as well as immunohistofluorescence were used to investigate the distribution of the neurotrophin-3 (NT3) in the adult rat cochlear nucleus. We found a widespread distribution of NT3 immunolabeled neurons throughout the three divisions of this nucleus. NT3-like immunoreactivity was clearly population-specific, with some cell groups heavily (various small neurons and granule cells) or moderately (large neurons of the ventral cochlear nucleus) stained, while others remained negative (a major fraction of medium and large neurons of the dorsal cochlear nucleus). Double-labeling experiments were performed using antibody against the glial fibrillary acid protein, a classic marker for mature astrocytes. This colocalization study revealed that NT3 immunoreactivity was also present in a subpopulation of astrocytes, particularly in the glia limitans and their projections. Numerous small cells also colocalized NT3 together with the glial marker in the granule cell domain and in the molecular cell layer of the dorsal cochlear nucleus. These results suggest that NT3 may exist in widespread populations of adult cochlear nucleus neurons as well as in glial cells. This abundant distribution of NT3-like immunoreactivity implies that this neurotrophin may have an important role in the continued maintenance of mature cochlear nucleus and makes it an attractive candidate for playing a role in regulation or stabilization of neuronal circuits in this nucleus.

Helicobacter pylori and gastric cancer. An endoscopic series.

In a series of 92 patients with gastric cancer who had biopsies of the antrum and fundus, we compared the 65 patients with Helicobacter pylori (71%) with the 27 negative patients. No difference was observed for age, gender or histology (intestinal or diffuse). Significant differences concerned location (11% of H. pylori positive patients had a cancer at the cardia or fundus vs 44%), the presence of a normal mucosa (3% vs 30%) and atrophy in the antrum (53% vs 17%). Seven of the ten patients with a normal mucosa had a cancer located at the cardia (p < 0.05) and in nine of the eleven patients younger than fifty, the cancer was of the diffuse type (p < 0.005). Thus, patients with H. pylori and gastric cancer differ from those uninfected. Of future concern is the large increase in cancers of the cardia, a cancer unassociated with H. pylori.

Age-related changes in GFAP-immunoreactive astrocytes in the rat ventral cochlear nucleus.

The age-related changes in the ventral cochlear nucleus (VCN) as revealed by glial fibrillary acid protein (GFAP) immunoreactivity were analyzed in the following age groups: 3-, 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. A cartographic and a quantitative analysis showed a significant increase in the number of GFAP positive astrocytes during the first year of life and a significant decrease in older rats. We also observed an age-induced modification in the spatial distribution of GFAP positive astrocyte. In the anterior part of the VCN of the 3- and 6-month-old rats, we observed a significant decrease in the rostro-caudal as well in the dorso-ventral axes. In the posterior part of the VCN, a significant decrease in the dorso-ventral axis could be also observed, but no significant difference in the spatial distribution was obtained in the rostro-caudal axis. In older rats, the distribution appeared homogeneous throughout the nucleus. Additionally, aging was associated with a significant increase in GFAP positive astrocyte sizes, except for immunolabelled astrocytes in the granule cell layer. The different levels of GFAP expression occurring in the VCN during normal aging could reflect a progressive decline of cellular activity in the VCN, without severe cell degeneration or synaptic loss.