Intestinal helminthic infections: a narrative review to guide the hepatogastroenterologist.

Intestinal helminthic infections are not uncommon in Western Europe, mainly due to modern travel, emigration and globalization. Moreover, some helminthic infections are endemic in Western Europe and are part of the everyday clinical practice. The hepatogastroenterologist should therefore recognize and manage these patients or at least refer them to appropriate reference centers. Signs and symptoms are often unspecific or even absent. Discerning the disease at an early stage avoids expensive diagnostic testing, life-threatening complications and in some cases even further spread of the disease. This review article aims to guide the hepatogastroenterologist when suspecting a helminthic infection by addressing the most prevalent symptoms, summarizing the most probable associated helminthic entities, highlighting practical steps in diagnosis and available treatments.

Prevalence of double incontinence in patients with fecal incontinence undergoing anorectal manometry and discriminating factors.

Background: Double incontinence (DI) is the concomitant presence of incontinence for urine and stool. Aim of this study is to assess prevalence of DI in patients with fecal incontinence (FI) undergoing Ano-Rectal Manometry (ARM) in a tertiary care center and to identify factors discriminating between both. Methods: Medical records of consecutive patients referred for ARM for FI during 2 years at University Hospital Brussels were retrospectively reviewed. Results from ARM, presence of diarrhea, diseases from recto-anal or peri-anal region, prior abdominal, proctological or urological surgery and neurological comorbidities were recorded. Results: Of 101 enrolled patients, 77% suffered from solitary FI and 23% from DI. Diarrhea was more common in DI vs. FI (43,5% vs. 15,4%, P=.008), as was the presence of neurological comorbidities (34.8% vs. 10.3%, P=.009) and urological interventions (21.7% vs. 1.3%, P=.002). In respect to women only, more urological interventions were performed (20% vs. 0%, P=.006) and more diseases from recto-anal or peri-anal region were encountered in DI vs. FI (35.0 % vs. 12.5 %, P= .045). In men, neurological disorders were significantly more common in DI (100.0% vs. 3.3%, P=.002). Conclusions: This study identified gender-specific patterns of comorbidities in FI and DI. ARM had no distinctive value between FI and DI in men and women. A prospective study should provide more information on patients at risk for incontinence and help to identify distinct features between FI and DI in men and women.

Belgian consensus on irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

The prevalence of disorders of the gut-brain axis in type 2 diabetes mellitus patients with metabolic dysfunction-associated fatty liver disease: an observational study.

BACKGROUND AND STUDY AIM: Disorders of the gut-brain axis (DGBI) and metabolic dysfunction-associated liver disease (MAFLD) are frequently diagnosed and exhibit pathophysiological similarities. This study aimed to estimate the prevalence of DGBI in type 2 diabetes mellitus (T2DM) patients with MAFLD. PATIENTS AND METHODS: In this single center, observational study, in adults with T2DM demographics, diabetes-related parameters and liver tests were recorded. MAFLD was defined by the presence of hepatic steatosis on imaging. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed based on Rome IV criteria. Quality of life (QOL), anxiety levels and depression levels were documented by validated questionnaires. RESULTS: We included 77 patients, 44 with and 33 without steatosis. There were no significant differences in age, body mass index (BMI), waist circumference, HbA1c levels or metformin use between groups. IBS was significantly more prevalent in the liver steatosis group (9/44 vs. 2/33, p = .037), while a similar trend was observed for FD (9/35 vs. 2/31, p = .103). No differences were found in anxiety, depression and overall QOL. However, QOL subscales for health worry, food avoidance and social reaction were significantly higher in the liver steatosis group. CONCLUSIONS: In otherwise comparable T2DM patients, DGBI, and especially IBS, are more prevalent in the presence of MAFLD. This difference could not be attributed to increased levels of anxiety or depression. Future research should target the underlying pathophysiological mechanisms.

Diagnostic approach to chronic diarrhoea and recent insights in treatment of functional diarrhoea including irritable bowel syndrome.

Chronic diarrhoea is a common clinical problem with a plethora of possible causes and underlying pathophysiological mechanisms. The value of diagnostic assessment by laboratory testing, stool analysis, evaluation of bile acid malabsorption, endoscopy, breath testing and radiological imaging techniques is discussed. The decision to focus investigations on excluding certain pathologies remains a matter of clinical judgement. Functional diarrhoea and irritable bowel syndrome (IBS) being the most frequent causes of chronic diarrhoea, recent insights in the role of dietary management, management of dysbiosis by pre-, pro- and antibiotics and faecal microbiota transplantation, as well as targeted treatment by spasmolytics, 5-HT3 receptor antagonists and eluxadoline will be reviewed.

Prevalence of and impact of pantoprazole on nocturnal heartburn and associated sleep complaints in patients with erosive esophagitis.

Studies in the United States have revealed that gastroesophageal reflux disease (GERD) patients often suffer from nocturnal symptoms, sleep disturbance, and impaired quality of life. In a large subset of patients, these symptoms persist in spite of acid suppressive therapy. The aim of the present study was to assess the prevalence of heartburn and associated sleep complaints and the response to standard medical therapy with pantoprazole in primary and secondary care esophagitis patients in Belgium. Questionnaires were provided to consecutive patients presenting to primary and secondary care physicians with esophagitis. The questionnaire evaluated the presence of typical reflux symptoms, alarm symptoms, risk factors, and sleep quality impairment as a result of reflux episodes. Results are shown as mean ± standard deviation and compared by Student's t-test or chi-square test. A total of 4061 primary and 5261 secondary care patients (50% female, mean age 53 ± 0.2 years, body mass index of 25.7 ± 0.1 kg/m(2) ) were recruited. Eighty-four percent of patients reported sleep disturbance attributable to nighttime reflux, including typical nighttime supine reflux symptoms (72%), difficulties to fall asleep (39%), waking up during the night (45%), morning fatigue (35%), and reflux symptoms when waking up in the morning (47%). Mild, moderate, or severe nighttime heartburn were reported by, respectively, 30, 35, and 12%, and these numbers were 26, 28, and 6% for nighttime regurgitation. Alcohol (19%), smoking (22%), higher esophagitis grades (grades 2, 3, and 4 in, respectively, 31, 7, and, 7%), alarm symptoms (27%), and more severe heartburn and regurgitation during daytime were all significantly associated with all dimensions of sleep disturbance (P < 0.0001). Obesity was only related to symptoms in supine position and when waking up (P < 0.0001). After 1.4 ± 0.0 months of treatment with pantoprazole, any sleep disturbance had improved in more than 75% of patients, with resolution of nighttime heartburn and regurgitation in, respectively, 75 and 83%. The majority of patients presenting with reflux symptoms and esophagitis in primary or secondary care experience nighttime heartburn and regurgitation, and sleep disturbance by nighttime symptoms is present in 84%. Smoking, alcohol use, higher grades of esophagitis, more severe typical reflux symptoms during daytime, and the presence of alarm symptoms are risk factors for GERD-related sleep disturbance. On standard therapy with pantoprazole, nighttime symptoms improved in more than 75%. These observations support a direct relationship between GERD and sleep disturbance.

Prolonged IL-1beta exposure alters neurotransmitter and electrically induced Ca(2+) responses in the myenteric plexus.

BACKGROUND Infection and inflammatory diseases of the gut results in profound changes of intestinal motor function. Acute administration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) was shown to have excitatory and neuromodulatory roles in the myenteric plexus. Here we aimed to study the effect of prolonged IL-1beta incubation on the response of myenteric neurones to different stimuli. METHODS Longitudinal muscle myenteric plexus preparations (LMMP's) of the guinea pig jejunum were incubated for 24 h in medium with or without IL-1beta. After loading with Fluo-4, calcium imaging was used to visualize activation of neurones. The response to application of serotonin (5-HT), substance P (SP) and ATP or to electrical fibre tract stimulation (eFTS) was tested. Expression of nNOS, HuD, calbindin and calretinin was compared by immunohistochemistry. KEY RESULTS IL-1beta concentration-dependently influenced the neuronal responsiveness and duration of the [Ca(2+)](i) rises to 5-HT and ATP, while it also affected the Ca(2+)-transient amplitudes induced by 5-HT, ATP and SP. Ca(2+)-transients in response to eFTS were observed in significantly more neurones per ganglion after IL-1beta (10(-10) and 10(-11) mol L(-1)). Peak [Ca(2+)](i) rise after eFTS was concentration-dependently decreased by IL-1beta. The duration of the [Ca(2+)](i) rise after eFTS was prolonged after IL-1beta 10(-12) mol L(-1). IL-1beta (10(-9) mol L(-1)) incubation did not affect the number of nNOS, calretinin and calbindin expressing neurones, nor did it induce neuronal loss (HuD). CONCLUSIONS & INFERENCES In this study, IL-1beta differentially modulates the neuronal response to eFTS and neurotransmitter application in the myenteric plexus of guinea pigs. This cytokine could be implicated in the motility disturbances observed during gastrointestinal inflammation.

Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia.

The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI-SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI-SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI-SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson's linear correlation, multiple regression analysis, chi-square and Student's t-tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation (r = 0.26), nausea/vomiting (r = 0.19), fullness/satiety (r = 0.20), bloating (r = 0.21) and lower abdominal pain (r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety (r = -0.27), bloating (r = -0.23), heartburn/regurgitation (r = -0.21), and upper abdominal pain (r = -0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety (P < 0.05). At different cut-off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI-SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear.

Influence of intra-oesophageal capsaicin instillation on heartburn induction and oesophageal sensitivity in man.

Heartburn is the most typical gastro-oesophageal reflux disease (GERD) symptom. The transient receptor potential vanilloid receptor-1 (TRPV(1)) is a candidate mediator of heartburn. Exposure of TRPV(1) to capsaicin is characterized by activation, followed by desensitization. Our aim was to investigate the effect of intra-oesophageal capsaicin instillation on oesophageal symptom perception (activation) and on sensitivity to oesophageal acid perfusion and oesophageal balloon distention (desensitization). In a first protocol (n = 10), saline or capsaicin solution were instilled in the mid-oesophagus and symptoms were rated at 5-min intervals for 60 min. In a second study (n = 10), oesophageal 0.1 N hydrochloric acid perfusion was performed 60 min after pretreatment with saline, low or high dose capsaicin. In a third study (n = 10), sensitivity to oesophageal balloon distention was determined before and at 30-min intervals up to 90 min after pretreatment with saline, low or high dose capsaicin. Areas under the curve (AUC) for symptom intensities under different conditions were calculated and compared with Kruskal-Wallis test. Oesophageal capsaicin instillation induced transient symptoms of retrosternal and epigastric burning in a dose-dependent fashion. After oesophageal capsaicin or saline instillation, there was no difference in symptom pattern and intensities induced by oesophageal acid perfusion. After oesophageal capsaicin or saline instillation, sensitivity to oesophageal balloon distention and oesophageal compliance were not significantly altered. Oesophageal instillation of the TRPV(1) receptor agonist capsaicin induces symptoms of retrosternal and epigastric burning in a dose-dependent fashion. Pretreatment with capsaicin does not desensitize the oesophagus to acid perfusion or to balloon distention.

Intestinal immune activation in presumed post-infectious functional dyspepsia.

Functional dyspepsia (FD) symptoms may develop after an acute gastroenteritis. In post-infectious (PI) irritable bowel syndrome, persisting low-grade colonic inflammation and increased enterochromaffine cells (EC) counts have been reported. The aim was to compare signs of inflammation and EC hyperplasia on duodenal biopsies in presumed PI-FD and unspecified-onset (U-)FD. Duodenal biopsies were obtained in 12 U-FD and 12 PI-FD (on average 13 months after the acute event) patients. The presence of intra-epithelial, intravillar, and the number of CD3, CD4, CD8 and CD68+ cells per crypts, and the mean number of Chromogranine A (CA) positive cells per villus were compared. We also measured gastric emptying and assessed proximal stomach function with a barostat. Data are shown as mean +/- SEM. Focal aggregates of T cells and focal CD8+ aggregates, were found in PI-FD but not in U-FD patients (respectively 5/12 vs 0/12, P = 0.02 and 5/9 vs 0/11, P < 0.01). In patients with focal aggregates, gastric emptying was delayed (189 +/- 37 min vs 98 +/- 11 min, P = 0.002). The number of CD4+ cells per crypt (0.52 +/- 1.6 vs 1.22 +/- 2.18, P = 0.04), and the number of intravillar CD4+ cells (0.5 +/- 0.2 vs 2.7 +/- 0.7, P = 0.01) were reduced, while the number of CD68+ cells per crypt was increased (0.64 +/- 0.13 vs 0.40 +/- 0.05, P = 0.03) in PI-FD. The number of EC and CA were comparable. PI-FD is associated with persisting focal T-cell aggregates, decreased CD4+ cells and increased macrophage counts surrounding the crypts. This may indicate impaired ability of the immune system to terminate the inflammatory response after acute insult.

Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man.

Ghrelin increases gastric tone in the fasting state and enhances gastric emptying in gastroparesis. The aims of the study were to evaluate the effect of ghrelin on postprandial gastric tone and on meal-induced satiety in health. Ten healthy volunteers underwent a barostat study on two occasions. After determination of intra-abdominal pressure (minimal distending pressure, MDP), isobaric volume measurement was performed for 90 min at MDP + 2 mmHg. After 20 min, ghrelin (40 microg) or saline was administered i.v. over 30 min in a double-blind-randomized cross-over design, followed 10 min later by a liquid meal (200 mL, 300 kcal). Stepwise isobaric distentions (+2 mmHg per 2 min) were performed 60 min after the meal. Data (mean +/- SEM) were compared using paired Student's t-test and ANOVA. Separately, a satiety drinking test (15 mL min(-1) until satiety score 5) was performed on 10 subjects twice, after treatment with placebo or ghrelin. Ghrelin infusion significantly inhibited gastric accommodation (mean volume increase adjusted means 108.0 +/- 50 vs 23.0 +/- 49 mL, P = 0.03, ANCOVA with the premeal postinfusion volume as covariate) and reduced postprandial gastric volumes (197.2 +/- 24.6 vs 353.5 +/- 50.0 mL, P = 0.01). Pressures inducing perception or discomfort during postprandial gastric distentions were not altered. During satiety testing, ghrelin did not alter nutrient volume ingested till maximal satiety (637.5 +/- 70.9 vs 637.5 +/- 56.2 mL, ns). Ghrelin administered during the meal significantly inhibits gastric accommodation in health, but this is not associated with early satiation.

Immune dysfunction in patients with functional gastrointestinal disorders.

There is increasing evidence for involvement of the immune system in functional gastrointestinal disorder (FGID), including onset after acute gastrointestinal infections, genotypes resulting in altered cytokine expression and abnormal presence of immune cells. Our aim was to assess cellular and humoral immune responses in (i) FGIDs, compared to healthy subjects and (ii) acute vs unspecified onset FGIDs. Lymphocytic [interleukin (IL)-5, IL-10, IL-13 and interferon gamma (IFN-gamma)] and monocytic [IL-10, IL-12, tumour necrosis factor (TNF)-alpha] cytokine production was characterized at baseline and after stimulation with phytohemagglutinine and anti-CD28 or lipopolysaccharide (LPS) in controls (n = 32), irritable bowel syndrome (IBS) (n = 30), functional dyspepsia (FD) (n = 23) and non-cardiac chest pain (NCCP) (n = 15). Serum IL-6 and IL-10 concentrations were compared, and the immunophenotype was assessed using fluorescent-activated cell sorter. Findings were compared for acute vs unspecified onset FGID. Compared to controls, stimulated lymphocyte expression of IL-5 and IL-13 was enhanced in IBS, FD and NCCP (all P < 0.05). Conversely, the stimulated monocytic IL-12 and lymphocytic IL-10 expression were reduced in IBS and FD, while IFN-gamma expression was also reduced in FD patients. Except for an increase in the numbers of CD3(+)CD45RA(+)CD45RO(+) cells, no distinct cellular profile was detected. Patients with a presumed acute onset of their symptoms had higher serum IL-10 levels and more CD3(+)CD45RA(+)CD45RO(+) cells, while TNF-alpha levels following stimulation with LPS were higher in FD patients reporting an acute onset. A shift towards a Th2 cytokine profile is present in FGID, while the cellular immunophenotype remains largely unchanged. Further research is indicated and could provide new therapeutic strategies for these disorders.

Influence of buspirone on gastric sensorimotor function in man.

BACKGROUND: Previous studies have suggested involvement of 5HT(1) receptors in the control of gastric tone. AIM: To study the effect of buspirone, a 5HT(1A) agonist, on gastric sensorimotor function in healthy volunteers. METHODS: Ten healthy volunteers (six males and four females, ages 20-29 years) participated in a barostat study evaluating the influence of single oral doses of buspirone (5, 10, 20, 30 and 40 mg) on tone and sensitivity of the proximal stomach. In addition, the effect of placebo or the three lowest doses of buspirone on gastric emptying was assessed using a solid and liquid gastric emptying breath test. RESULTS: Compared to preadministration volumes, buspirone increased proximal stomach volumes in a dose-dependent manner, with significant fundic relaxation after 30 and 40 mg doses (intra-balloon volume increases of respectively 258 +/- 80 mL and 273 +/- 49 mL, P < or = 0.05). Pressure thresholds during gastric distention were not altered, but corresponding intraballoon volumes were significantly increased after 30 and 40 mg doses (respective discomfort volumes 596 +/- 73 vs. 791 +/- 87 mL and 630 +/- 73 vs.741 +/- 60 mL, both P < 0.05). Buspirone significantly slowed solid and liquid gastric emptying at the 20-mg dose. CONCLUSION: Buspirone dose-dependently relaxes the proximal stomach in the fasting state and decreases the gastric emptying rate in healthy volunteers.

Reproducibility and symptomatic predictors of a slow nutrient drinking test in health and in functional dyspepsia.

Impaired accommodation to a meal has been recognized as a pathophysiological mechanism in functional dyspepsia (FD). Based on observations in tertiary care patients, the drinking test has been proposed as a non-invasive tool to estimate accommodation. Our aim was to assess the reproducibility of the drinking test and its correlation with demographic, symptomatic and pathophysiological parameters in secondary care FD patients and healthy controls. Thirty-four healthy controls and 78 FD patients completed a drinking test (3 respectively 2 times), a gastric emptying study and an FD symptom questionnaire. Factors influencing maximal volume and gastric emptying were determined, and the reproducibility of the drinking test was investigated. The maximal satiety was reached at a lower volume in patients (489 +/- 276 and 503 +/- 248 mL for first and second test respectively vs 937 +/- 428 and 1048 +/- 421 mL, P < 0.0001). The ingested amount depended on age, sex and baseline FD symptom score. Patients' sex, final satiety score, total score for stomach complaints at screening and total symptom score before test accounted for the total symptom score after the test. The slow nutrient drinking test confirms its possible role as an attractive non-invasive and reproducible tool for the diagnosis of impaired accommodation and for the assessment of treatment responsiveness.

Mechanisms of serotonergic agents for treatment of gastrointestinal motility and functional bowel disorders.

Most of the body's serotonin is released in the gut where it plays an important role in the control of gastrointestinal (GI) motility, sensitivity and muscle tone by activating different receptor subtypes. This review focuses on the known effects of selective serotonin reuptake inhibitor and serotonin receptor agonists and antagonists on the sensorimotor function of the GI tract and describes the therapeutic potential of these actions for GI motility and functional bowel disorders.

Neural mechanisms of early postinflammatory dysmotility in rat small intestine.

Although human postinflammatory dysmotility is known, so far animal studies have primarily investigated changes during inflammation. Here, we focused on postinflammatory changes in rat jejunal myenteric plexus and jejunal motility. Evolution of ethanol/2,4,6-tri-nitrobenzene sulphonic acid (TNBS)-induced inflammation was assessed histologically and by measuring myeloperoxidase activity (MPO). Electromyography and immunohistochemistry were performed 1 week after ethanol/TNBS and also after N(G)-nitro-L-arginine methyl ester (L-NAME) administration. Ethanol/TNBS induced a transient inflammation, with normalization of MPO and histological signs of an early phase of recovery after 1 week. The number of cholinergic neurones was not altered, but myenteric neuronal nitric oxide synthase (nNOS)-immunoreactivity was significantly lower in the early phase of recovery after TNBS compared with water (1.8 +/- 0.2 vs 3.5 +/- 0.2 neurones ganglion(-1), P < 0.001). Interdigestive motility was disrupted with a loss of phase 1 quiescence, an increase of migrating myoelectric complex cycle length, a higher number of non-propagated activity fronts and a decrease of adequately propagated phase 3 s after TNBS. Administration of L-NAME resulted in a similar disruption of interdigestive motility patterns. In the early phase of recovery after ethanol/TNBS-induced jejunal inflammation, a loss of motor inhibition occurs due to a decrease of myenteric nNOS activity. These observations may provide a model for early postinflammatory dysmotility syndromes.

Impaired gastric accommodation and its role in dyspepsia.

The accommodation reflex is an important mechanism of normal gastric physiology. In functional dyspepsia, impairment of accommodation has been found in 40% of cases, but it has been described in several other upper gastrointestinal disorders, such as diabetic gastropathy and postfundoplication syndrome. This review focuses on the pathways involved in the normal accommodation reflex, the relevance of impaired gastric accommodation as a cause of morbidity and the methods used to assess gastric accommodation in humans. The available medical and therapeutic strategies based on the actual knowledge of the physiology and pharmacology of the accommodation reflex are outlined, with a focus on the role of nitrergic neurones and serotonergic receptors.

Pathophysiology of functional dyspepsia.

Functional dyspepsia is a highly prevalent symptom complex and a heterogeneous disorder. Recent studies showed potential associations between specific pathophysiologic disturbances and dyspeptic symptoms. Delayed gastric emptying reported in about 30% of patients with functional dyspepsia is associated with the symptoms of postprandial fullness, nausea, and vomiting. Impaired gastric accommodation present in 40% of functional dyspepsia patients is found to be associated with early satiety. Hypersensitivity to gastric distension is observed in 37% of functional dyspepsia patients and associated with the symptoms of postprandial pain, belching, and weight loss. Psychosocial factors and altered response to duodenal lipids or acid have also been identified as pathophysiologic mechanisms.

Diversification within grapevine cultivars goes through chimeric states.

Vitis vinifera 'Pinot' clones were analysed at 50 microsatellite loci to assess intravarietal genetic diversity. When analysing leaf tissue DNAs, polymorphism mainly resulted from the appearance of a third allele when two were expected for heterozygous loci in a diploid species. The sequencing of the three microsatellite alleles at two loci has confirmed their simultaneous presence in the leaf tissues. A hypothesis explaining the triallelic profiles at a locus is the presence of a periclinal chimera meristem structure, in which genetically different cell layers coexist. The periclinal chimeric state of two Vitis vinifera 'Pinot gris' clones was confirmed by splitting and analysing the genotypes resulting from L1 and L2 cell layers in progeny derived from self-fertilization, in root tissues, and in plants regenerated from somatic embryogenesis. Prevalence of chimerism in polymorphic clones observed in a collection of 145 accessions belonging to 'Pinot gris', 'Pinot noir', Pinot blanc', 'Pinot meunier', and 'Pinot moure' cultivars was demonstrated. The accumulation of somatic mutations and cell layer rearrangements allowed us to deduce the relationships between the various genotypes and to open a way for understanding the diversification process and the phylogeny in the 'Pinot' group.