PubMed Health⌕ Search

Biomedical subjects

J Tack

Publications and source records attributed to J Tack.

At least 91 records · Page 5Linked to original sources

Causes and treatment of functional dyspepsia.

Functional dyspepsia is a clinical syndrome defined by upper abdominal symptoms without identifiable cause by conventional diagnostic means. Recent studies have established that functional dyspepsia is a heterogeneous disorder in which different pathophysiologic disturbances underlie different symptom profiles. Delayed gastric emptying is associated with postprandial fullness, nausea, and vomiting; impaired accommodation is associated with early satiety and weight loss; and hypersensitivity to gastric distention is associated with epigastric pain, belching, and weight loss. The pathogenesis of functional dyspepsia is unknown but may be postinfectious in a subgroup of patients. The role of psychological disturbances and of duodenal hypersensitivity requires further study. Treatment of the underlying pathophysiologic abnormality seems logical, but options for pharmacotherapy are limited to acid suppression, prokinetic drugs, and antidepressants. Psychotherapy can be considered for refractory patients. Several novel drug therapies are under evaluation.

Dyspepsia↗

Imaging of neuronal activity in the gut.

Over the past few years, several groups have used voltage-sensitive dyes or calcium-indicator dyes to optically monitor the activity of several enteric neurons simultaneously. Some of the initial practical problems have been solved and these studies have successfully shown the spread of electrical activation within the enteric neuronal circuitry in cultures and in ex vivo specimens. The basic mechanisms underlying voltage-sensitive dye or calcium-indicator signals and their relation to changes in membrane potential need further investigation. Application of these techniques will provide more insight into neuronal interaction and spread of activation. The ability to simultaneously record activity in other cells in the same focal plane offers the potential to investigate how the integrated neuronal circuits are linked to effector cells in their close neighbourhood. Progress in optical imaging of enteric neuronal activity should ultimately lead to a better knowledge of gastrointestinal physiology and pathophysiology.

Animals↗

Effect of intranasal sumatriptan on gastric tone and sensitivity to distension.

Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by relaxing the gastric fundus. The aim of this study was to verify the efficacy of intranasal administration of sumatriptan on gastric sensory motor function, in order to provide a new pharmacotherapeutic approach to functional dyspepsia. Thirteen healthy subjects were investigated twice on separate days. A gastric barostat was used to study the effect of placebo and sumatriptan, 20 mg intranasally, on basal fundic tone. In addition, stepwise isobaric distensions were performed and perception was measured before and after administration of drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan caused a small, but short-lasting gastric relaxation and had no significant effect on sensitivity to distension and gastric compliance. Unlike the subcutaneous formulation, the intranasal administration of sumatriptan had no effect on gastric sensory motor functions, and this probably reflects a low biovailability of intranasally administered sumatriptan.

Administration, Intranasal↗

Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats.

The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia.

Animals↗

Free cytosolic Ca2+ recordings from myenteric neurones in multilayer intestinal preparations.

The ability to simultaneously monitor different myenteric neurones in a multilayer preparation may enhance our understanding of the enteric nervous system. Longitudinal muscle myenteric plexus preparations were mounted in recording chambers with a coverslip base and loaded with Indo-1-AM. cytosolic Ca2+ concentration ([Ca2+]i); changes were recorded at room temperature with a confocal microscope. In addition to mechanical (pressure-ring) and pharmacological (nifedipine) reduction of muscle contractions, purpose-designed software was developed to reposition regions of interest and avoid artefacts. Confocal scanning permitted optical selection of single cell layers. High K+ depolarization, used to distinguish between excitable and nonexcitable cells, caused a synchronous [Ca2+]i rise in 84.3% of the ganglion cells. Acetylcholine, substance P and serotonin (all at 10(-5) mol L(-1)) induced transient [Ca2+]i changes in subpopulations of myenteric neurones (45.1%, 42.9 and 21.9%, respectively). In addition to immediate responses to agonists, delayed [Ca2+]i changes were also recorded, suggesting the presence of both directly activated and synaptically driven neurones. Functionally identified neurones and other cells in close apposition to the ganglia (interstitial cells of Cajal) could also be studied. This study demonstrates the potential of optical Ca2+ recordings to monitor spread of activity in myenteric neurones and to study their interaction with non-neuronal targets.

Acetylcholine↗

Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings.

BACKGROUND & AIMS: Gastroesophageal reflux can be acid, nonacid, pure liquid, or a mixture of gas and liquid. We investigated the prevalence of acid and nonacid reflux and the air-liquid composition of the refluxate in ambulant healthy subjects and patients with reflux disease (GERD). METHODS: Twenty-four-hour ambulatory recordings were performed in 30 patients with symptomatic GERD and erosive esophagitis and in 28 controls. Esophageal pH and impedance were used to identify acid reflux (pH drop below 4.0), minor acid reflux (pH drop above 4.0), nonacid reflux (pH drop less than 1 unit + liquid reflux in impedance), and gas reflux. RESULTS: The total rate of gastroesophageal reflux episodes was similar in patients and controls. Patients with GERD had a higher proportion (45% vs. 33%) and rate of acid reflux than controls (21.5 [9-35]/24 h vs. 13 [6.5-21]/24 h; P < 0.05). One third of reflux events was nonacid in both groups. Mixed reflux of gas and liquid was the most frequent pattern with gas preceding liquid in 50%-80% of cases. Pure liquid reflux was more often acid in patients with GERD than controls (45% vs. 32%; P < 0.05). CONCLUSIONS: Reflux of gastric contents was similarly frequent in patients with GERD and controls. Although there was no difference in the overall number of reflux episodes, more acidic reflux occurred in symptomatic patients with GERD, suggesting differences in gastric acid secretion or distribution.

Adult↗

Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.

BACKGROUND & AIMS: Hypersensitivity to gastric distention has been reported in functional dyspepsia, but its characteristics and relevance to symptoms remain unclear. The aim of this study was to define hypersensitivity to gastric distention and its association to specific symptoms in functional dyspepsia. METHODS: We used a gastric barostat to study sensitivity to gastric distention in 80 healthy subjects and in 160 functional dyspepsia patients. Demographic characteristics, gastric emptying, Helicobacter pylori status, gastric accommodation, and a dyspepsia symptom score were obtained from all patients and the relationship with visceral sensitivity was assessed using univariate and multivariate analysis. RESULTS: The increase of intra-balloon pressure over intra-abdominal pressure needed to induce discomfort or pain is the most appropriate expression of sensitivity to gastric distention because it yields a meaningful lower range of normal and it is independent from age and body mass index. Hypersensitivity to gastric distention was found in 34% of the patients, who did not differ from the other patients in demographic and other pathophysiological characteristics. Hypersensitivity to distention was associated with a higher prevalence of postprandial pain, belching, and weight loss. CONCLUSIONS: Hypersensitivity to gastric distention is present in a subset of functional dyspepsia patients. It is associated with symptoms of postprandial epigastric pain, belching, and weight loss.

Abdominal Pain↗

Functional dyspepsia symptoms, gastric emptying and satiety provocative test: analysis of relationships.

BACKGROUND: The correlation between symptoms and observed impaired function in functional dyspepsia is still inconsistent. The aims of the study were to obtain a measure of satiety by a meal test; to verify whether this compares with severity of symptoms assessed using a reproducible questionnaire; and to correlate the parameters of satiety test and gastric emptying with all the dyspeptic symptoms. METHODS: Fifty-two functional dyspepsia patients reported their symptoms on a standardized questionnaire that considered belching, bloating, early satiety, epigastric pain and burning, nausea, postprandial fullness and vomiting. They were monitored for gastric emptying of a solid caloric meal using a radionuclide technique and underwent a test to quantify meal-induced satiety by a liquid caloric meal. RESULTS: The number of kilocalories ingested during the satiety test until the occurrence of maximum satiety in healthy subjects was 110% higher than in the dyspeptic group (mean +/- s(mean): 1110 +/- 23 versus 532 +/- 56; P < 0.01). We found a significant positive correlation between gastric emptying rate and kcal of the satiety test (P < 0.01; r = 0.428). Logistic regression showed a significant inverse association between severity of early satiety-coded as absent, mild, moderate or severe, kcal of meal test (P = 0.01), and gastric emptying lag phase (P = 0.03). Bloating was associated directly with t(1/2) of gastric emptying (P = 0.03) and inversely with lag phase (P = 0.02). CONCLUSIONS: The satiety test gives a fine numerical measure of satiety and confirms the results of a symptoms questionnaire. Our study showed an indirect correlation between severity of early satiety--as measured by the satiety test, and gastric emptying rate, as well as an association between bloating and delayed gastric emptying.

Adult↗

Chronic middle ear disease and gastroesophageal reflux disease: a causal relation?

OBJECTIVE: To describe one patient with a puzzling therapy-resistant unilateral chronic otitis media, analyze his diagnosis, and describe three similar patients with the same symptoms and signs, i.e., a chronic ear problem together with gastroesophageal reflux disease (GERD). STUDY DESIGN: Thorough analysis of one patient with a chronic ear problem and GERD, both of which responded favorably after antireflux therapy consisting of omeprazole and conservative antireflux measures (raising the head of the bed by 20 to 25 cm, avoiding meals and drinks 3 hours before retiring, and other dietary and lifestyle modifications), and a search for more patients with similar coexisting conditions. SETTING: Tertiary referral center. METHODS: Patients with chronic ear problems and GERD were thoroughly analyzed by the otorhinolaryngologist and the gastroenterologist. The latter used endoscopy and Savary-Miller's classification of esophagitis, a 24-hour ambulatory dual esophageal pH monitoring, and esophageal manometry. RESULTS: Four patients were identified who had a chronic ear problem and simultaneous GERD. It is reasoned that the GERD leads to nasopharyngitis and this to a chronic ear problem. All the patients responded favorably to anti-GERD therapy. CONCLUSIONS: GERD may manifest itself as an extraesophageal manifestation, such as nasopharyngitis, leading to ear disease. Therapy-resistant chronic middle ear disease may be caused by GERD.

Adult↗

Reproducibility of gastric barostat studies in healthy controls and in dyspeptic patients.

OBJECTIVES: Gastric barostat studies are increasingly being performed, but their reproducibility and the most suitable study protocol have not been determined. The aim of this study was to verify the reproducibility of gastric sensitivity and accommodation testing in healthy and in dyspeptic subjects, and to compare stepwise and double random staircase distensions. METHODS: A total of 13 dyspeptic patients and 25 healthy control subjects underwent two successive studies. Sensory thresholds were assessed on a same-day/different-days protocol, using a stepwise (11/14 healthy subjects and 11/13 patients) or a double random staircase inflation (11/21 healthy subjects). In 10 healthy subjects, both methods were compared. Gastric accommodation was measured on different days in 13 patients and nine healthy subjects. Data (mean +/- SEM) were compared using the paired t test, and individual variability was expressed as the percent coefficient of variation. RESULTS: In healthy subjects, the thresholds for first perception and for discomfort were highly reproducible (p > 0.05) and the pressure thresholds showed a lower degree of variability than the volumes. Pressure thresholds quantified by stepwise showed lower variability than double random staircase inflation. In the patients, the sensory thresholds were unchanged between the sessions on the same and on different days (p > 0.05). Gastric accommodation also showed excellent reproducibility for both dyspeptic patients and healthy control subjects (p > 0.05). CONCLUSIONS: Both in dyspeptic patients and in healthy control subjects, gastric sensitivity and accommodation quantified by isobaric distensions show excellent reproducibility. Pressure and volume thresholds both are well reproducible, but the former shows less variability. Finally, the simplest stepwise protocol is better than the double random staircase to assess the gastric sensitivity to distension.

Adult↗

Composition of the postprandial refluxate in patients with gastroesophageal reflux disease.

OBJECTIVE: It is not known whether the characteristics of the postprandial refluxate in patients with gastroesophageal reflux disease (GERD) differ from those observed in normal subjects. The aim of this study was to characterize the postprandial refluxate in adult patients with GERD using combined intraluminal electrical impedance and pH measurements. METHODS: Postprandial gastroesophageal reflux was assessed in 16 patients with GERD and 15 controls. pH and intraluminal electrical impedance were used to identify acid and nonacid reflux of liquid, mixed (liquid + gas) or gas. RESULTS: Transient lower esophageal sphincter relaxations (TLESRs) and reflux of gastric contents were equally frequent in both groups. However, patients with GERD had more acid reflux [8 (4.7-10.5)/h vs 3.5 (2.6-6)/h, p < 0.05], and normal subjects had more nonacid reflux [5 (4.3-6.7)/h is 3 (1-3.5)/h, p < 0.05]. Gas reflux was less frequent in GERD than in controls (51% vs 68%; p < 0.05). Pure liquid reflux, however, was more frequent (40% vs 26%, p < 0.05) and twice as likely to be acid in GERD. During TLESRs, liquid acid reflux was more frequent in GERD than in controls. CONCLUSIONS: TLESRs and reflux of gastric contents are similarly frequent in patients with GERD and controls. However, patients with GERD have more acid reflux and less nonacid reflux. Differences in the air-liquid composition of the refluxate may contribute to the higher rate of acid reflux observed in these patients.

Acids↗

The role of acid and duodenal gastroesophageal reflux in symptomatic GERD.

OBJECTIVE: Mixed reflux of acid and duodenal contents frequently occurs in patients with gastroesophageal reflux disease (GERD). The aim of this study was to establish the contribution of acid and duodenal gastroesophageal reflux (DGER) to symptoms in patients with presumed GERD. METHODS: A total of 72 patients (37 women), mean age 45 yr (+/-2 yr), underwent 24-h ambulatory pH and Bilitec monitoring. Patients pressed a marker button when experiencing typical symptoms. For each symptom episode, minimal pH and maximal bilirubin optical density in a 2- or 4-min interval were calculated. For each patient, the symptom index (SI) and symptom-association probability for acid and for bile reflux were determined. RESULTS: A total of 544 symptom episodes were identified. Using a 2-min interval, 28% were associated with acid reflux, 9% with DGER, and 12% with mixed reflux. No significant difference was found when a 4-min interval was used. A positive SI for acid reflux was present in 21% of the patients and for DGER in 14%. All patients with a positive SI for DGER had also a positive SI for acid reflux. A positive symptom-association probability for acid reflux was present in 22% of the patients, for DGER in 7% of the patients, and for mixed reflux in 10% of the patients. CONCLUSIONS: Symptom episodes in patients with presumed GERD are more related to acid reflux than to DGER. DGER does not play a major role in producing typical esophageal symptoms.

Bilirubin↗

Perception of changes in wall tension of the proximal stomach in humans.

BACKGROUND: Hypersensitivity to distension of the stomach is a frequent finding in functional dyspepsia. During gastric distension studies both wall tension and elongation are increased. AIM: We wished to distinguish changes in wall tension from changes in elongation in the genesis of perception of mechanical stimuli originating from the proximal stomach in healthy subjects. SUBJECTS AND METHODS: Twenty six volunteers were studied using gastric barostat and antroduodenal manometry. In 14 subjects, stepwise isobaric and isovolumetric distensions were performed before and during erythromycin infusion. In all volunteers, on a separate occasion, phasic contractions of the proximal stomach were detected as intraballoon pressure increases during fixed volume inflation. These contractions were matched with perception changes during two 10 minute periods, before and during administration of erythromycin. RESULTS: Erythromycin significantly lowered the perception and discomfort thresholds during stepwise gastric distension. During fixed volume inflation, erythromycin increased the number and amplitude of fundic contractions and enhanced their perception from 51.1 (7.4)% to 64.0 (4.7)%. The proportion of perception score increases coinciding with fundic contractions increased from 47.3 (0.7)% to 81.5 (0.5)%. The amplitude of correctly identified isolated fundic pressure waves was higher compared with non-identified waves. CONCLUSIONS: These results support the hypothesis that changes in gastric wall tension may be involved in the genesis of symptoms originating from the stomach.

Adult↗

Functional Dyspepsia: Impaired Fundic Accommodation.

Functional dyspepsia is a heterogeneous disorder in which distinct pathophysiological abnormalities are present in subgroups of patients. Accommodation of the proximal stomach to a meal is impaired in 40% of patients with functional dyspepsia. This is associated with symptoms of early satiety and weight loss. The presence of early satiety as a relevant or severe symptom is a good predictor of impaired accommodation. Gastric barostat or proximal gastric ultrasound may confirm the presence of impaired accommodation after a meal. Sophisticated analysis of scintigraphic gastric emptying images or a simple caloric drinking test are under investigation in the diagnosis of impaired accommodation. It seems logical to have patients eat more frequent, smaller sized meals. Cisapride is the only well-evaluated form of pharmacological treatment for this condition, and has been withdrawn from the US market (see Important Note under Treatment, below). Small or preliminary studies suggest some benefit from buspirone or selective serotonin reuptake inhibitors (SSRIs).

Journal Article↗

Transient lower esophageal sphincter relaxations and esophageal body muscular contractile response in reflux esophagitis.

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients.

Adult↗