PubMed Health⌕ Search

Biomedical subjects

H D Allescher

Publications and source records attributed to H D Allescher.

At least 19 recordsLinked to original sources

[Achalasia--early diagnosis and treatment options].

Achalasia is a rare motility disorder of the distal esophagus, showing reduced or absent swallow induced relaxation of the lower esophageal sphincter region. The onset of the disease can be very slow and correct diagnosis might be delayed over years. Using exact medical history, upper GI endoscopy and barium swallow X-ray the achalasia can be suspected and can be confirmed by esophageal manometry. Other especially malignant diseases, which can imitate the clinical symptoms, have to be ruled out. Pneumatic balloon dilatation is therapy of first choice in achalasia. Especially in younger patients laparoscopic fundoplication with subsequent antireflux procedure should be offered early in the therapeutic algorithm when dilatation therapy fails. Medical therapy or intrasphincteric injection of botulinum toxin is only an alternative treatment for high risk patients, treatment failures or residual symptoms.

Barium Sulfate↗

Functional dyspepsia--a multicausal disease and its therapy.

Functional dyspepsia is a common chronic disorder with non-specific upper abdominal symptoms which can not be explained by organic or biochemical abnormalities. The dyspeptic symptoms are very compromising and bothersome and result in a substantial reduction of quality of life. The substantial direct and indirect medical and economical costs induce a high socioeconomic interest in the pathogenesis and the treatment options of this disease. Over the past 30 years several theories about the etiology of the symptoms in functional dyspepsia patients have been put forward. These include disorders of gastrointestinal motility, acid secretion, visceral hypersensitivity, adaptation and accommodation, Hp-infection, mucosal inflammation and finally genetic predisposition. There is increasing evidence that functional dyspepsia is a multi-causal disorder, which leads to altered processing of afferent information from the gastrointestinal tract to the CNS. Autonomic hypersensitivity and altered central processing could be a common phenomenon whereas motility changes, inflammation or altered secretion could increase neural afferent inputs. Treatment of this complex disorder could and should involve these different levels of symptom generation. Thus different approaches with anti-secretory, spasmolytic, prokinetic and anti-inflammatory effects and most preferably reduction of visceral hypersensitivity seem logical. This could explain the variety of drugs which show a positive symptomatic response. This could also offer the conclusion, whether a combination of these drugs could be clinically superior which remains to be proven. And this could offer a logical approach for the use of substances with a multi-target action, e.g. STW 5.

Diagnosis, Differential↗

STW 5 (Iberogast) and its individual herbal components modulate intestinal electrophysiology of mice.

STW 5 (Iberogast), a phytomedicine agent consisting of a fixed combination of nine individual plant extracts, is widely used in the treatment of dyspepsia and motility related disorders. Little if anything is known on the possible influence on electrophysiological properties of intestinal smooth muscle by which STW 5 causes its beneficial effects. The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of large and small intestine. For this purpose intracellular recordings of smooth muscle cell (SMC) of the circular muscle layer of different parts of mouse intestine were performed using standard microelectrode techniques. The resting membrane potential (RMP), excitatory and inhibitory neurotransmission in proximal colon, the frequency and the amplitude of slow waves in small intestine were investigated. The RMP of SMC was -46.4+/-3.8 mV, n=11 in the colon and -59+/-1.3 mV, n=15 in small intestine. STW 5 significantly depolarized the RMP of colonic (16.6+/-2.2 mV, n=6, p<0.05) and jejunal (9.6+/-1.6 mV, n=7, p<0.05) SMC. This depolarizing effect can be mainly attributed to the constituents of chamomile flower, Angelica root and greater celandine herb. Following the electrical field stimulations (EFSs), junction potentials are influenced in a distinct manner. Excitatory junctions potentials (EJPs) of the colon were not significantly reduced (13.1+/-4.8 vs. 10.1+/-2.8 n.s., n=6) but fast (fIJP) and slow (sIJP) inhibitory junction potentials of the murine colon are reduced significantly by STW 5 (fIJP: 21.6+/-8.1 vs. 11.6+/-2.1 and sIJP: 12.1+/-3.3 vs. 6.1+/-1.3 n=6, p<0.05). The basal frequency of small intestinal slow waves was 39.5+/-1.4 min(-1) and the amplitude was 23.1+/-0.9 mV, n=15. STW 5 significantly reduced amplitude and frequency of the slow waves (11.7+/-0.8 mV; 33.5+/-3.4 min(-1), n=6, p<0.05). This effect on slow waves represents the summation of effects of the nine individual phytoextracts. Whereas Angelica root and chamomile flower completely blocked the slow wave activity, bitter candy tuft increased the frequency and amplitude, greater celandine herb reduced frequency and amplitude of the slow wave, peppermint leaf reduced frequency and left amplitude unchanged and liquorice root, caraway fruit and lemon balm leaf had no effects in basic electrophysiological properties of SMC. This study demonstrates that STW 5 causes changes in SMC RMP, excitatory and inhibitory neurotransmission and slow wave rhythmicity. These effects represent a summation effect of different constituents of this phytotherapeuticum and prove that STW 5 has characteristic effects on intestinal electrophysiology.

Animals↗

CB1 and TRPV1 receptors mediate protective effects on colonic electrophysiological properties in mice.

CB1 and TRPV1 receptors modulate enteric neurotransmission and colonic inflammation. This study investigates early electrophysiological changes in distal colon of wild-type and receptor deficient mice after an inflammatory insult set by dinitrobenzene sulfonic acid (DNBS). Colitis was induced by DNBS in CB1(-/-) mice, TRPV1(-/-) mice, and their respective wild-type littermates. Electrophysiological properties consisting of membrane potentials and electrically induced inhibitory junction potentials (IJP) of circular smooth muscle cells were evaluated at different time points. Additionally a histological colitis severity score was evaluated in CB1(+/+) and CB1(-/-) mice 24 h after DNBS. Inflammation caused spontaneous atropine insensitive rhythmic action potentials in CB1(-/-) and TRPV1(-/-) mice but not in wild-type animals. This indicates that membrane stability is disturbed, which in turn indicates a lack of protective mechanisms. Focal electrical neuronal stimulation of the myenteric plexus induced IJP in the smooth muscle cells. Twenty-four hours after initiation of inflammation, the duration of the IJP is prolonged in all animals, indicating disturbances within neuromuscular interaction. In CB1(-/-) mice, it is interesting that the duration of IJP was significantly extended, as compared to CB1(+/+) mice pointing toward missing protective mechanisms in the CB1(-/-) mice. Inflammatory insults in the mouse colon induce reproducible changes in the electrophysiological properties and such changes correlate with duration of colitis. In mutants, these electrophysiological changes display different patterns, suggesting the lack of protective properties for neuromuscular interactions and membrane stability.

Action Potentials↗

Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine.

BACKGROUND: Herbal preparations like STW 5 (Iberogast) are widely used drugs in the treatment of dyspepsia and motility-related disorders of the gastrointestinal tract. STW 5 is a phytotherapeutic agent consisting of a fixed mixture of 9 individual plant extracts. The electrophysiological mechanisms of action of STW 5 remain obscure. AIM: The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of the small intestine. For this purpose, the resting membrane potential (RMP) and the slow wave rhythmicity of smooth muscle cells of mouse small intestine were observed. METHODS: Intracellular recordings of smooth muscle cells of the circular muscle layer of mouse small intestine were performed using standard microelectrode techniques. After dissection of the mucosa, the small intestine was placed in an organ bath and a microelectrode was applied on a circular smooth muscle cell. The RMP and the amplitude of slow waves were measured in millivolts. RESULTS: The RMP of smooth muscle cells was -59 +/- 1.3 mV. This RMP was significantly depolarized by STW 5 (9.6 +/- 1.6 mV); the depolarizing effects can be mainly attributed to the constituents of matricariae flos, angelicae radix and chelidonii herba. The basal frequency of small intestinal slow waves was 39.5 +/- 1.4 min(-1) and the amplitude was 23.1 +/- 0.9 mV. STW 5 significantly reduced the amplitude and frequency of the slow waves (11.7 +/- 0.8 mV; 33.5 +/- 3.4 min(-1)). This effect on slow waves represents the sum of the effects of the 9 phytoextracts. Whereas angelicae radix and matricariae flos completely blocked slow wave activity, Iberis amara increased the frequency and amplitude, chelidonii herba reduced the frequency and amplitude of the slow waves, mentae piperitae folium reduced the frequency and left amplitude unchanged and liquiritae radix, carvi fructus and melissae folium had no effects. CONCLUSION: Herbal extracts cause changes in smooth muscle RMP and slow wave rhythmicity, up to reversible abolition, by blockade of large conductance Ca2+ channels and other not yet identified mechanisms. In herbal preparations like STW 5 these effects add up to a total effect and this study indicates that herbal preparations which are widely used in dyspepsia and motility-related disorders have characteristic, reproducible, reversible effects on small intestinal electrophysiology.

Animals↗

[Reflux disease therapy].

The frequency of gastroesophageal reflux disease is on a constant rise in western countries. Reflux therapy can be subdivided into the treatment of acute erosive reflux esophagitis and the subsequent recurrence prophylaxis, and into the treatment of non-erosive reflux disease as well as the atypical reflux symptoms. Based on conventional large-scale studies, a highly effective therapy is available which offers virtually complete acid blockade using proton pump inhibitors (PPI) of the prazole type. Used for acute treatment, they offer a cure for reflux esophagitis and freedom from symptoms in approx. 90% of the cases, while also showing high efficacy in recurrence prophylaxis. Conversely, the rate of side effects, particularly serious ones, is very low and the long-term safety of this therapy has been good. Since the risk of erosive reflux esophagitis recurring is > 80% without PPI therapy, the majority of the patients will require a long-term, potentially even life-long therapy with PPI. Other therapeutic options are being discussed as alternatives to such long-term prophylaxis. In selected cases, surgical therapy by laparoscopic fundoplication is one option. Alternatively, endoscopical anti-reflux procedures are increasingly coming into use; their merit in long-term prophylaxis however, cannot yet be evaluated. Whenever PPI therapy does not lead to complete freedom from symptoms, an alternative therapeutic approach should be given consideration even in patients with atypical reflux symptoms. The therapy of the Barrett's esophagus, a potentially long-term sequelae of reflux disease, will not be dealt with in this overview, as it is the subject of a separate presentation.

Anti-Ulcer Agents↗

Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: multicenter study of the Gatekeeper Reflux Repair System.

BACKGROUND AND STUDY AIMS: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of expandable polyacrylonitrile-based hydrogel prostheses into the esophageal submucosa to augment the lower esophageal sphincter (LES). PATIENTS AND METHODS: For this study, data from two prospective, nonrandomized European multicenter trials were pooled. Sixty-nine GERD patients with heartburn and regurgitation and abnormal esophageal acid exposure (24-h pH < 4.0 for > 4 % of the total time) who had responded to proton-pump inhibitor (PPI) therapy were recruited, and 68 were treated with up to six prostheses placed at the gastroesophageal junction. Patients underwent esophageal manometry, endoscopy, 24-h pH-metry, and symptom scoring at intake and 1, 3, and 6 months after the procedure. RESULTS: A total of 77 procedures were performed in 67 patients, and a total of 270 prostheses were placed (mean 4.3 per procedure). At 1 and 6 months, 80.4 % and 70.4 % of the prostheses were retained, respectively. At 6 months, 24-h pH-metry outcomes with pH < 4.0 for > 4.0 % of the time decreased from 9.1 % to 6.1 % (n = 45; P < 0.05). Median LES pressure increased significantly from 8.8 mmHg at baseline to 13.8 mmHg at 6 months (n = 42, P < 0.01). Median GERD heartburn-related quality-of-life scores improved significantly from 24.0 to 5.0 (n = 53, P < 0.01) in patients no longer receiving PPI therapy. Two serious adverse events (3.0 %) occurred. Both patients recovered uneventfully. Prostheses were endoscopically removed from one patient without any adverse events. CONCLUSIONS: The Gatekeeper Reflux Repair System is a safe endoscopic treatment modality that significantly improves GERD symptoms and has objective effects on acid reflux.

Adult↗

Lower esophageal sphincter pressure in patients with gastroesophageal reflux diseases and posture and time patterns.

Gastroesophageal reflux disease is caused predominantly by lower esophageal sphincter insufficiency. Reports suggest that it is possible to distinguish between two main mechanisms causing reflux: low basal sphincter pressure leading to free reflux, mostly occurring at night in the supine position, and increased transient lower esophageal sphincter relaxations with normal or increased resting pressure leading to reflux during the day in an upright position. Lower esophageal sphincter pressure (LESP)-- s determined by stationary pull-through manometry--was compared to profiles of acidic reflux measured by 24-h pH monitoring in 207 patients with proven gastroesophageal reflux disease. Differences in LESP were not significant among patients with reflux predominantly during the day in an upright position and those with reflux predominantly at night in a supine position (16.1 +/- 7.4 mmHg versus 15.1 +/- 7.8 mmHg; t-test: P = 0.355). For both patterns of LESP, there was a slight negative correlation with the amount of acidic reflux (determined as a percentage of time with pH < 4). Pearson correlation coefficients were -0.196 for upright refluxers and -0.137 for bipositional/supine refluxers (P = 0.006 and P = 0.049, respectively). As there are no differences in LESP with regard to posture or time patterns of acidic reflux it seems unlikely that upright reflux is associated with increased LESP, whereas supine reflux manifests due to a hypotensive LESP. Alternatively, it may be concluded that stationary pull-through manometry is inadequate for determining the cause of gastroesophageal reflux disease and is therefore of limited use in its routine diagnosis.

Adult↗

Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission in mouse colon.

The effects of cannabinoid receptor agonists and antagonists on smooth muscle resting membrane potentials and on membrane potentials following electrical neuronal stimulation in a myenteric neuron/smooth muscle preparation of wild-type and cannabinoid receptor type 1 (CB1)-deficient mice were investigated in vitro. Double staining for CB1 and nitric oxide synthase (neuronal) was performed to identify the myenteric CB1-expressing neurons. Focal electrical stimulation of the myenteric plexus induced a fast (f) excitatory junction potential (EJP) followed by a fast and a slow (s) inhibitory junction potential (IJP). Treatment of wild-type mice with the endogenous CB1 receptor agonist anandamide reduced EJP while not affecting fIJP and sIJP. EJP was significantly higher in CB1-deficient mice than in wild-type littermate controls, and anandamide induced no effects in CB1-deficient mice. N-arachidonoyl ethanolamide (anandamide), R-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]- 1,4-benzoxazin-6-yl]-1-naphtalenylmethanone, a synthetic CB1 receptor agonist, nearly abolished EJP and significantly reduced the fIJP in wild-type mice. N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-caroxamide (SR141716A), a CB1-specific receptor antagonist, was able to reverse the agonist effects induced in wild-type mice. SR141716A, when given alone, significantly increased EJP in wild-type mice without affecting IJP in wild-type and EJP in CB1-deficient mice. Interestingly, SR141716A reduced fIJP in CB1-deficient mice. In the mouse colon, nitrergic myenteric neurons do not express CB1, implying that CB1 is expressed in cholinergic neurons, which is in line with the functional data. Finally, excitatory and inhibitory neurotransmission in the mouse colon is modulated by activation of CB1 receptors. The significant increase in EJP in CB1-deficient mice strongly suggests a physiological involvement of CB1 in excitatory cholinergic neurotransmission.

Animals↗

Endogenous CCK depresses contractile activity within the ascending myenteric reflex pathway of rat ileum.

The ascending excitatory reflex is an important part of the myenteric reflex. In order to study the ascending neural pathways, isolated segments of rat ileum were stimulated by electrical stimulation of the gut wall (20 V, 3 pulses per second, 1 ms) using platinum electrodes. The excitatory contractile response was recorded using perfused manometric side-hole tubing located 2 and 4 cm orally to the stimulation site. The contractile response to electrical stimulation was abolished by atropine (10(-6) M) or hexamethonium (10(-4) M). The excitatory response increased after administration of the cholecystokinin A (CCK(A)) receptor antagonists lorglumide (3x10(-6) M: +44.1%), devazepide (10(-8) M: +19.4%; 10(-7) M: +30.0%) and SR-27897 (10(-10) M: +21.8%, 10(-8) M: +47.0%, P<0.05, n=8). However, the CCK(B) receptor antagonist L-365,260 also caused a significant increase in the oral excitation (10(-6) M: +27.4%). sCCK-8 caused a significant reduction in the ascending response (10(-8) M: -11.5%) and induced spontaneously occurring contractions at doses ranging from 10(-10)-10(-6) M. CCK-9 significantly increased the ascending response (10(-7) M: +10.9%, P<0.05). However, caerulein (10(-10) M: -25.9%, 10(-8) M: -26.8%; P<0.01) and pentagastrin (10(-10) M: -20.2%, P<0.05; 10(-8) M: -23.7%, P<0.01; 10(-6) M: -28.3%, P<0.001) reduced the ascending contractile response significantly. These data, obtained with potent and highly specific CCK receptor antagonists, demonstrate an inhibitory role of endogenously released CCK within the ascending neural pathway. The data further suggest that exogenously applied CCK-related peptides have different effects on the myenteric reflex which might be due to excitation of the different involved neurons (short and long ascending inter- and motorneurons) in an unphysiological order. Thus in experiments investigating more complex neuronal circuits, experiments with antagonists should be regarded as more specific.

Animals↗

High interobserver variability in endosonographic staging of upper gastrointestinal cancers.

Mostly based on results of experienced examiners, endoscopic ultrasound (EUS) has been reported to be highly accurate for locoregional staging of upper gastrointestinal cancers. However, data on interobserver variability among EUS examiners, depending on their experience levels, is sparse. A study was therefore conducted to analyse well-documented videotapes of EUS examinations of 108 patients with resected cancers of the esophagus (n = 55) or stomach (n = 53) in a strictly blinded fashion by 5 examiners, all of whom were experienced in EUS (more than 300 examinations: n = 3, more than 100 examinations: n = 2). Besides the individual accuracy rates in cancer staging, a kappa-statistic was calculated to check for interobserver variability. Under the conditions described, the staging accuracy of all investigators was lower than that usually achieved under clinical routine conditions. The mean T staging accuracy was 41.1 % +/- 9.4 and 46.9 % +/- 5.4 in gastric and esophageal cancers, respectively. For N-staging the respective values were 47.9 % +/- 5.1 (stomach) and 67.7 % +/- 5.4 (oesophagus). Kappa-values were above 0.4 only in the staging of non-invasive esophagogastric tumours of the N0 and T1-category, corresponding to a fairly good agreement among the five investigators. Differences depending on experience levels could not be consistently found. Hence, it can be concluded that endosonographic cancer staging performed in a blinded manner results in a low accuracy and high interobserver variability even among experienced examiners.

Endosonography↗

Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time and clinical sequelae. A prospective observational study.

BACKGROUND: In the diagnosis and treatment of biliary disorders, establishing percutaneous transhepatic biliary drainage (PTBD) is an invasive procedure that can potentially lead to infectious complications in both the short and long-term. We therefore prospectively analysed the time course and spectrum of biliary bacteria in patients undergoing PTBD. METHODS: Forty-nine patients (19 F, 30 M; mean age 64 years) with malignant (65%) or benign (35%) biliary disorders were included, 20 of whom had a newly established PTBD (group A), while the remaining 29 had already had their PTBD in situ (group B) for a mean of 8 months. Bacteriological analyses of bile and blood were carried out, and clinical symptoms and laboratory values were obtained. RESULTS: Biliary bacteria were found in 60% of cases during the initial PTBD placement, and 24 h later this rate had already increased to 85%; two or more microorganisms were found in 40% initially and in 70% after a few days. At later PTBD exchanges, bacteriobilia was found in 100%, with all patients harbouring multiple organisms. Whereas the initial spectrum was mixed, Escherichia coli and enterococci (97% each), Klebsiella (73%) and Bacteroides species (37%) later predominated; Candida increased initially from 15% to 80%, but later decreased to 30%. Clinical signs of cholangitis were observed in 30% initially (no sepsis), but decreased to 6% at later exchanges. CONCLUSIONS: Bacteriobilia is initially a frequent, and later a regular, event in PTBD; however, clinically significant complications are rare during the long-term course and limited to the initial, more invasive, phase of PTBD. A knowledge of the bacterial spectrum is important for selecting appropriate antibiotic coverage if complications arise and/or major interventions such as surgery are planned.

Adult↗

Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment.

BACKGROUND: It has been suggested that intrasphincteric injection of botulinum toxin (BTX) may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP) and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection). METHODS: Forty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients). Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX). The symptoms were assessed using a global symptom score (0-10), which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy. RESULTS: After BTX injection, there was a significant reduction in LOSP (before, 38.2+/-11.3 mmHg; 1 week after, 20.5+/-6.9 mmHg; 1 month after, 17.8+/-6.8 mmHg; P < 0.001). The global symptom score and symptom subscores (dysphagia, regurgitation, chest pain) were significantly decreased after 1 week and 1 month. When the beneficial effects following BTX injection were compared (untreated vs. pretreated), neither changes in LOSP nor beneficial effects on the symptom scores significantly differed. After 6 months, 67.7% of all treated patients were still in symptomatic remission (subgroups: previously untreated patients, 61.5%, n = 26; prior dilatation, 71.4%, n = 7; prior myotomy, 71.4%, n = 7; prior BTX, 73.9%, n = 8). CONCLUSIONS: BTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

Adult↗

[Diagnosis of gastroesophageal reflux].

Around 10-20% of the population suffer from the hallmark symptoms of heartburn, regurgitation, sour burping and retrosternal pain. Based on their characteristic medical history alone, such patients can usually be presumed to have gastroesophageal reflux disease (GERD). In around 30-50% of them, the endoscopic examination will reveal the typical erosions and ulcerations in the esophagus. In addition to the clinical symptoms, endoscopy plays a central role in diagnosing GERD. An endoscopy is always indicated whenever these warnings symptoms are present. In patients with persistent reflux problems, endoscopy is indicated to diagnose erosive reflux esophagitis. This procedure should include a routine biopsy taken distal to the Z-line to enable histological detection of the metaplasia associated with Barrett's esophagus. Although the majority of patients exhibit the classical symptoms and respond to acid suppression therapy, endoscopy may not find erosions (non-erosive reflux disease NERD). In these cases, further diagnostic steps must be taken to verify the diagnosis of gastroesophageal reflux disease. There are patients, moreover, who exhibit unclear, uncharacteristic reflux symptoms, such as respiratory diseases with bronchial asthma, chronic bronchitis, chronic cough or ENT problems like posterior laryngitis and globus sensation (a lump in the throat). In these uncertain cases and in patients with NERD, 24-hour pH monitoring can verify and objectify and acid gastroesophageal reflux. An association can then be made between acid reflux and symptomatology. As an alternative, trial therapy with a proton pump inhibitor can help identify patients who have acid-related problems and symptoms. Other functional tests such as radiographic examination, manometry or scintigraphy are less well suited, if at all, for primary diagnostics of gastroesophageal reflux disease.

Barrett Esophagus↗

Okadaic acid inhibits relaxant neural transmission in rat gastric fundus in vitro.

The aim of the present study was to characterize the influence of the phosphatase type 1 and 2A inhibitor okadaic acid on non-adrenergic, non-cholinergic (NANC) neurotransmission in the rat gastric fundus. Okadaic acid (10-6 M), an inhibitor of protein phosphatases 1 and 2A, did not show any influence on the basal tonus or on a contraction plateau induced by 5-HT (10-7 M) within 30 min of observation. When okadaic acid (10-6 M) was applied 10 min prior to 5-HT (10-7 M), the contraction plateau of serotonin was unchanged. To investigate the inhibitory neurotransmission, the muscle strips were pre-contracted using 5-HT (10-7 M), and inhibitory stimuli were applied at the contraction plateau, which was stable over 30 min. The inhibitory effects of vasoactive intestinal peptide (VIP), nitric oxide (NO) and electrical field stimulation (EFS, 40 V, 0.5 ms, frequencies ranging from 0.5 to 16 Hz) were examined. When okadaic acid (10-6 M) was applied prior to EFS-induced NANC relaxation, significant attenuation of the inhibitory response was demonstrated (16 Hz: control: -92.4 +/- 1.9%; okadaic acid 10-7 M: -60.7 +/- 6.1%; okadaic acid 10-6 M: -25.3 +/- 3.4%; n=11; P < 0.01). By contrast, neither the concentration-dependent inhibitory actions of VIP (10-11-10-8 M) (VIP 10-8 M: -100%; VIP 10-8 M + okadaic acid 10-6 M: -89.9 +/- 8.3%; n=8; n.s) nor that of diethylamine nitric oxide (DEA-NO) (3 x 10-7-10-4 M) (DEA-NO 10-4 M: -95.3 +/- 8.4%; DEA-NO 10-4 M + okadaic acid 10-7 M: -98.3 +/- 6.3%; DEA-NO 10-4 M + okadaic acid 10-6 M: 96.5 +/- 7.6%; n=9; n.s.) on 5-HT induced contraction were altered by pre-incubation with okadaic acid (10-6 M). This is the first report that supports the concept that protein phosphatases 1 and 2A may contribute to the regulation of rat gastric fundus motility. The protein phosphatase inhibitor okadaic acid significantly reduces electrically induced inhibitory NANC responses, while leaving direct muscular effects of the inhibitory NANC neurotransmitters VIP and NO unaffected - suggesting a neural site of action. The potential roles of protein phosphatases on NANC neurotransmission remain to be clarified in detail, as this might offer a new pathway for modulating smooth-muscle function.

Animals↗

Endoscopic treatment of a Zenker's diverticulum using argon plasma coagulation in a patient with massive cachexia and esophageal obstruction: a case report and review of literature.

A case report is presented of an 86-year-old man in a very poor general condition with a 10-year history of a Zenker's diverticulum as a cause of a complete obstruction of the esophagus with subsequent aphagia and massive cachexia. Because of high surgical risk and contraindications to general anesthesia, an approach with the flexible endoscope to perform cricopharyngeal myotomy was undertaken. Several attempts with the flexible endoscope by experienced investigators had been performed until the esophageal inlet was intubated and argon plasma coagulation could be applied in several sessions to divide the tissue bridge between the esophagus and the Zenker diverticulum to successfully restore the pharyngoesophageal passage.

Aged↗