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Biomedical subjects

H D Allescher

Publications and source records attributed to H D Allescher.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Rationale and selection for combined procedures in colonic dysplasias and T1 carcinomas. Laparoscopic-endoscopic local wall excision and segment resection].

Combined endoscopic-laparoscopic procedures may offer an interesting therapeutic option in cases of benign colonic lesions and early T 1 carcinoma where endoluminal resection is not feasible, but oncological resection is not (yet) required. Combined procedures such as the laparoscopically assisted endoscopic resection, the endoscopically assisted laparoscopic wedge or transluminal resection, or the segmental resection can be performed. Experience with this technique is still limited, but has shown that the invasiveness can be reduced by endoscopically guided local excision. If it is possible to keep the incidence of secondary operations low, combined laparoscopic/endoscopic interventions could occupy a valuable place in the therapeutic spectrum.

Adult↗
PubMed2000

Distinct expression of splice variants of neuronal nitric oxide synthase in the human gastrointestinal tract.

BACKGROUND & AIMS: Changes of neuronal nitric oxide synthase (nNOS) expression have been linked to several human gastrointestinal disorders such as achalasia, diabetic gastroparesis, and hypertrophic pyloric stenosis. They could be caused by differential transcriptional control or alternative splicing generating different nNOS proteins. The aims of this study were to characterize 5'-splice variants, promoter usage, and site-specific expression of nNOS in the human gastrointestinal tract. METHODS: 5'-Splice variants were characterized by immunoblotting, reverse-transcription polymerase chain reaction, 5'-rapid amplification of complementary DNA ends, and Southern blotting. Genomic analysis was performed by rapid amplification of genomic ends, followed by reporter gene assays. RESULTS: Six different 5'-splice variants of nNOS-messenger RNA were identified showing specific expressions at various sites of the human gastrointestinal tract. Three variants encode for nNOSalpha, which has a specific N-terminal PDZ/GLGF domain and interaction sites for regulatory proteins. Two variants encode for nNOSbeta and 1 for nNOSgamma, which both lack the protein-binding domains of nNOSalpha. In addition to 2 known first exons, a novel first exon of human nNOS with a separate functionally active downstream promoter and multiple binding sites for transcription factors was identified and characterized. CONCLUSIONS: Six 5'-mRNA splice variants of nNOS encoding 3 different nNOS proteins are expressed in the human gut. The differential expression of these proteins could be implicated in different biological functions.

Alternative Splicing↗
PubMed2000

Endomorphin-1 and -2, endogenous ligands for the mu-opioid receptor, inhibit striated and smooth muscle contraction in the rat oesophagus.

Recently, morphological evidence for an interaction of autonomic nerve fibres and extrinsic motor innervation of the rat oesophagus has emerged. The aim of the present study was to investigate the possible influence of endogenous and exogenous opioids on rat oesophageal smooth and striated muscle function in vitro. The entire oesophagus (excluding the lower oesophageal sphincter) with both Nervi (Nn) vagi, including the Nn recurrentes, was dissected and placed in an organ bath (100 mL, 37 degrees) with oxygenated Krebs-Ringer buffer. Contractile activity was measured in a longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm distant from the oesophagus. Vagal stimulation (VS), applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response that was completely blocked by 10(-6) M tetrodotoxin. The first part consisted of a tetanic striated muscle contraction, as it was abolished by tubocurarine (10(-5) M, n=5) but unaffected by atropine (10(-6) M, n=3) or hexamethonium (10(-4) M, n=4). In contrast, the second part was completely inhibited by hexamethonium (10(-4) M) and atropine (10(-6)M), whereas tubocurarine (10(-5) M) showed no influence, indicating a stimulation of preganglionic nerve fibres supplying oesophageal smooth muscle (muscularis mucosae) via relays in myenteric ganglia. In order to characterize opioid influence on the oesophageal striated and smooth muscle contractility, the following experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous mu-opioid-receptor agonists, reduced the contractile response of the striated (EM-2, -25.1+/-5.3%; n=16), and the smooth muscle (EM-2, -81.9+/-3.3%; n=11). Both effects were reversible by the opioid receptor antagonist naloxone (10(-6) M) and therefore, mediated via opioid receptors. Neither SNC-80, an agonist on the delta-opioid-receptor, U-69593, an agonist on the kappa-opioid-receptor, nor nociceptin, an agonist at the ORL1 (opioid receptor-like) receptor, had a significant effect on the striated muscle contraction. In contrast to SNC-80, U-69593 and nociceptin inhibited smooth muscle contraction but this relaxation could not be antagonized by naloxone. None of the opioid receptor antagonists used had an effect on basal tonus or muscle contraction following VS. Our data provide evidence for an autonomic modulation of vagal motor innervation of the striated and smooth oesophageal muscle. Endomorphin-1 and -2, both selective mu-opioid receptor agonists, cause an inhibition of striated and smooth muscle response which is reversible by naloxone, an opioid receptor antagonist. The location of the mu-opioid receptor still has to be established.

Animals↗
PubMed2000

Mechanisms of alpha,beta-methylene atp-induced inhibition in rat ileal smooth muscle: involvement of intracellular Ca2+ stores in purinergic inhibition.

1. In order to investigate purinergic effects on rat ileal smooth muscle, we used alpha,beta-methylene ATP (alpha,beta-MeATP), ATP, ADP and UTP. alpha,beta-Methylene ATP and ATP were the only agonists that caused a concentration-dependent inhibition of carbachol-precontracted smooth muscle. The inhibitory effect of alpha,beta-MeATP was completely blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) mol/L), a selective antagonist of the P2X > > P2Y receptor. 2. Using reverse transcription-polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation. 3. The alpha,beta-MeATP-induced inhibition was blocked in a concentration-dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10(-7) mol/L), 4-aminopyridine (10(-4)mol/L), glibenclamide (10(-5) mol/L) and tetraethylammonium (10(-3) mol/L). 4. The alpha,beta-MeATP-induced inhibition was unaffected by pretreatment with atropine (10(-6) mol/L), phentolamine (10(-6) mol/L), propranolol (10(-6) mol/L), nitrendipine (10(-7) mol/L), pertussis toxin (10(-6) mol/L) NG-nitro-L-arginine (3 x 10(-4) mol/L) and tetrodotoxin (10(-6) mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G-protein involvement in purinergic-mediated inhibition. 5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+-ATPase inhibitor. The inhibitory effect of alpha,beta-MeATP was completely abolished after depletion of the intracellular Ca2+ stores. 6. This is in contrast with the effects seen for neurotensin, where neurotensin-induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin-sensitive non-adrenergic, non-cholinergic inhibition in rat ileal smooth muscle. 7. According to our results, the inhibitory effect of alpha,beta-MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G-protein-independent activation of an apamin-sensitive K+ channel and requires filled intracellular Ca+ stores.

Adenosine Triphosphate↗
PubMed2000

Modulatory effect of endogenous and exogenous opioids on the excitatory reflex pathway of the rat ileum.

The ascending excitatory reflex is part of the peristaltic reflex, an important participant in intestinal propulsion. The aim of this study was to characterize the role of different opioid receptors in the ascending reflex through exogenous application of non-selective (Met-enkephalin) and selective opioid agonists (mu-PLO17, delta-DPDPE, kappa-U-50, 488) as well as selective opioid receptor antagonists (mu: CTOP-NH(2), delta: ICI-174,864, kappa: Nor-Binaltorphimine). Metenkephalin (IC(50): 0.06 microM) and morphine (IC(50): 1.8 microM) inhibited the ascending reflex response concentration-dependently. Both the mu-selective agonist PLO17 (IC(50): 0.83 microM, n =11) and the kappa-selective agonist U-50,488 (IC(50): 0.68 microM, n =8) concentration-dependently inhibited the magnitude of the ascending contractile reflex response, whereas the delta-agonist DPDPE (10(-10)-10(-6)M) had no significant effect. In contrast, the latency of the response (time interval between start of the stimulus and onset of the contraction) was significantly prolonged by PLO17 > morphine > Met-enkephalin > DPDPE, whereas U-50,488 showed no effect. When the effect of the receptor-specific antagonists was tested, only CTOP-NH(2)and Nor-BNI caused a significant increase of the contractile response, whereas ICI-174 864 was ineffective. On the other hand, CTOP-NH(2)> ICI-174 864 decreased the latency significantly but the kappa-receptor agonist Nor-BNI had no influence. Thus, mu- and kappa-receptors seem to be involved in regulating the contraction strength of the ascending reflex, whereas both mu- and delta-receptors seem to be involved in the timing of the reflex response.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Long-term outcome in patients with advanced hilar bile duct tumors undergoing palliative endoscopic or percutaneous drainage.

OBJECTIVE: Advanced tumors of the hepatic duct bifurcation (Klatskin tumors) present problems to the endoscopist in deciding which procedure to use for palliative treatment of the resulting cholestasis--endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD), or both. There are technical difficulties with all forms of treatment for stenoses in the hilar region and intrahepatic bile ducts, and there are as yet no clear data on which type of drainage is feasible or preferable. SUBJECTS: 59 consecutive patients (30 men, 29 women; mean age 71 years) underwent palliative treatment for malignant hilar bile duct tumors of Bismuth stages II-IV during a three-year period (1992-94). METHOD: A retrospective analysis was carried out, and long-term follow-up data were obtained from telephone interviews with the patients, relatives, or referring physicians. RESULTS: The 59 patients were treated using ERCP (n = 20) or PTBD (n = 39). Three died within 30 days, and six were lost to follow-up. Clinically adequate drainage was achieved in 78% (n = 46) of the total patient group. Patient survival was a median of six months (range 0.5-38), and was slightly longer when the primary drainage procedure was successful (7.5 months). Initial complications occurred in 11% after ERCP and in 33% after PTBD, with a 30-day mortality of 5%. After the initial intervention, five patients who received ERCP treatment had to be switched to PTBD during the longer-term course. Three of these five patients died within 30 days of the PTBD insertion. CONCLUSIONS: Palliative treatment in patients with advanced Klatskin tumors is still suboptimal, even when combined endoscopic and percutaneous techniques are used in the same institution, allowing treatment to be tailored to the individual patient's needs. There is therefore a need for improvements in existing forms of treatment, as well as for the development of new forms of treatment.

Adult↗
PubMed2000

Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes.

BACKGROUND: It has been claimed in several prospective studies that endoscopic ultrasonography (EUS) is highly accurate in the locoregional staging of pancreatic cancer. However, the value of the EUS criteria for the diagnosis of vascular involvement is less well established. To totally exclude potential bias introduced by the availability of prior information, a completely blinded analysis of videotapes of patients with cancer of the pancreatic head was therefore conducted. METHODS: Videotape sequences of 75 patients with cancer of the head of the pancreas with surgical confirmation or unequivocally positive angiography demonstrating vascular invasion were reevaluated without any clinical data or information from other imaging studies. Involvement of the vascular system (portal vein with confluence, superior mesenteric vein, celiac axis) was assessed on EUS with special emphasis on EUS parameters of the tumor-vessel relationship. RESULTS: The overall sensitivity and specificity of EUS in the diagnosis of venous invasion were 43% and 91%, respectively, when using predetermined parameters (visualization of tumor in the lumen, complete obstruction, or collateral vessels). If the parameter "irregular tumor-vessel relationship" had been added to these criteria, the sensitivity would have risen to 62%, but the specificity would have fallen to 79%. The only vascular system that could be properly visualized by EUS was the portal vein/confluence area. The positive and negative predictive values for the single parameters chosen to diagnose portal venous involvement were as follows: 42% and 33% for irregular tumor-vessel relationship, 36% and 34% for visualization of tumor in the vascular lumen, 80% and 28% for complete vascular obstruction, and 88% and 18% for collateral vessels. CONCLUSIONS: In a completely blinded evaluation of the EUS diagnosis of vascular invasion by cancer of the head of the pancreas it was not possible to find suitable morphologic parameters with clinically useful sensitivity and specificity values (over 80%).

Adult↗
PubMed2000

Modern imaging methods versus clinical assessment in the evaluation of hospital in-patients with suspected pancreatic disease.

OBJECTIVE: Various modern imaging procedures such as endoscopic retrograde cholangiopancreatography (ERCP), computed tomography (CT), and endoscopic ultrasonography (EUS) have been shown to be highly accurate in the diagnosis of specific disorders of the pancreas. However, prior information often causes bias in the interpretation of these results. Little information is available concerning the value of these examinations in the primary and differential diagnosis of suspected pancreatic disease-particularly in comparison with clinical evaluation, including laboratory tests and transabdominal ultrasound (TUS). METHODS: Clinical and imaging information (EUS, ERCP, and CT) was collected for 184 inpatients who were referred over a 5-yr period for evaluation of suspected pancreatic disease. On the basis of patient history, laboratory tests, and the results of routine TUS, one gastroenterologist, who was unaware of any of the other procedures or the final diagnosis, made a presumptive clinical diagnosis. CT and ERCP images and EUS videotapes were then analyzed by three different and independent examiners, who had the same clinical information except for the TUS results, but were completely blinded to the results of the other examinations and the patients' diagnoses. The final diagnoses were obtained by surgery, histology, and cytology, plus a follow-up of at least 1 yr (mean 35 months) in all noncancer cases. RESULTS: The final diagnoses were: normal pancreas (n = 36), chronic pancreatitis without a focal inflammatory mass (n = 53) or with a focal inflammatory mass (n = 18), and pancreatic malignancy (n = 77). Clinical evaluation, including ultrasonography, achieved a sensitivity for pancreatic disease of 94% but a specificity of only 35%. The figures for the sensitivity and specificity of the three imaging procedures were 93% and 94%, respectively, for EUS; 89% and 92% for ERCP; and 91% and 78% for CT (p < 0.05 for the specificity of clinical assessment vs all three imaging tests, p > 0.05 for comparison of the three imaging procedures). In the differential diagnosis between cancer and chronic pancreatitis as well as between malignant and inflammatory tumors, there was no difference among clinical assessment and the three imaging tests. CONCLUSIONS: In a group of patients with a high suspicion of pancreatic disease, little additional sensitivity in the diagnosis of pancreatic disease is provided by sophisticated imaging procedures such as EUS, ERCP, and CT, in comparison with clinical assessment including laboratory values and TUS. However, the specificity can be substantially improved. To confirm the diagnosis, one of the three examinations is needed, depending on the suspected disease and local expertise. The imaging procedures should be performed in a stepwise fashion for specific purposes, such as exclusion of pancreatic disease and the planning of treatment in chronic pancreatitis and pancreatic cancer.

Adolescent↗
PubMed2000

Pathophysiology and pharmacological treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a gastroenterologist's practice. Gastroesophageal reflux describes the retrograde movement of gastric contents through the lower esophageal sphincter (LES) to the esophagus. It is a common, normal phenomenon which may occur with or without accompanying symptoms. Symptoms associated with GERD include heartburn, acid regurgitation, noncardiac chest pain, dysphagia, globus pharyngitis, chronic cough, asthma, hoarseness, laryngitis, chronic sinusitis and dental erosions. The introduction of fiberoptic instruments and ambulatory devices for continuous monitoring of esophageal pH (24-hour pH monitoring) has led to great improvement in the ability to diagnose reflux disease and reflux-associated complications. The development of pathological reflux and GERD can be attributed to many factors. Pathophysiology of GERD includes incompetent LES because of a decreased LES pressure, transient lower esophageal sphincter relaxations (TLESRs) and deficient or delayed esophageal acid clearance. Uncomplicated GER may be treated by modification of life style and eating habits in an early stage of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2) blockers, prokinetics and proton pump inhibitors. Although these drugs are effective, they do not necessarily influence the underlying causes of the disease by improving the esophageal clearance, increasing the LESP or reducing the frequency of TLESRs. The following article gives an overview regarding current concepts of the pathophysiology and pharmacological treatment of GERD.

Antacids↗
PubMed2000

Inhibition of small conductance K+ -channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus.

The aim of this study was to investigate the effects of melatonin on rat gastric fundus smooth muscle. Melatonin (10(-4) to 10(-3) M) had no effect on the basal tone of gastric smooth muscle. After precontraction with carbachol (10(-6) M) or serotonin (10(-7) M), melatonin caused a concentration dependent inhibitory action. The half maximal effect on serotonin-induced contraction was found with 1.12 +/- 0.86 x 10(-5) M of melatonin. Increasing concentrations of melatonin (10(-5) to 10(-3) M) resulted in a right shift of the serotonin concentration response curve (10(-10) to 10(-5) M). This inhibitory effect of melatonin was partially blocked in the presence of apamin (10(-10) to 10(-7) M), a specific blocker of the small conductance calcium-dependent potassium channel, but not in the presence of other potassium channel blockers like charybdotoxin (10(-8) M), glibenclamide (l0(-5) M), or tetraethylammonium (ODQ, 10(-4) M). The inhibitory effect was not changed in the presence of the neuronal blocker tetrodotoxin (10(-6) M), the selective P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) M), the nitric-oxide synthase inhibitor N-nitro-L-arginine (3 x 10(-4) M), or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (10(-4) M), suggesting that neither the purinergic, nitrergic, nor guanylate cyclase pathways were involved. We further investigated inhibitory responses to electrical field stimulation (EFS) at different frequencies under non-adrenergic, non-cholinergic (NANC) conditions on a serotonin-induced contraction in the presence of melatonin (10)-5 to 10(-4) M). Melatonin significantly reduced these inhibitory NANC responses in higher (8-32 Hz), but not lower (05-4 Hz), frequencies (16 Hz without melatonin, 103 +/- 6.3%; melatonin 10(-5) M, 80.4 +/- 7.5%; melatonin 10(-4) M, 39.1 +/- 17.1%). Melatonin had no effect on contractile responses induced by EFS under basal tone. These results demonstrate that the inhibitory effect of melatonin in rat gastric fundus smooth muscle is apamin sensitive, but is not affected by other potassium channel blockers. This suggests that melatonin may be another transmitter candidate for the apamin sensitive responses within the gastrointestinal tract.

Animals↗
PubMed2000

The teleconsultation service ENDOTEL. Implementation and first experiences.

The multimedia teleconsultation service ENDOTEL launches in May 2000 with its asynchronous component. In the initial phase, three hospitals and four general practitioners use the service to consult a specialist in the domain of gastroenterology and endoscopy. By validation of the patient information, i.e. videos, voice clips, still images and text, the experts can decide the further proceeding, for example, whether a patient shall be transported to a specialized hospital or not (cost-saving). We report about the experiences during the initiation and the first months of operation.

Endoscopy, Gastrointestinal↗
PubMed1999

[Prospective Epidemiologic Study of Epigastric Discomfort (PRESTO). Ground work and preliminary results].

BACKGROUND AND OBJECTIVE: Symptoms of dyspepsia (indigestion; upper abdominal discomfort) are one of the most frequent reasons for consulting a general practitioner or internist. Yet there are no up-to-date national data on the epidemiology and course of this symptom complex. PATIENTS AND METHODS: In an open, prospective, multicentre, epidemiological study (PRESTO) 3016 patients with the suspected diagnosis of "functional dyspepsia" (1228 males, 1788 females, mean age 50 +/- 15 years) were followed for 2 years by 983 physicians in private practice (general practitioners or specialists in internal medicine). Patients with proven gastro-oesophageal reflux or peptic ulcer were excluded. Treatment was at the discretion of the physician. Patients were seen after one month (if under treatment) and then at 6, 12, 18 and 24 months. In addition to personal data, (1) symptoms, diagnosis and treatment of the dyspepsia, (2) socioeconomic aspects and (3) any limitations and the quality of life of each patient were recorded in a standard manner. RESULTS: At the first interim analysis more than half the patients judged there situation to be one of "chronic stress" or having to cope with a stressful event; nearly 50% thought this to be the cause of the symptoms. Concomitant illnesses were present in 63% of patients. Oesophagogastroduodenoscopy with subsequent medication was performed in 20.6%, a trial of medication (usually drugs stimulating gastric motility) in 65%. No medication was initially given to 14.4% of patients. The most common symptoms were feeling of fullness (92.9%, epigastric pressure sensation (91.5%) and flatulence (87.4%). CONCLUSION: These preliminary results indicate that a large epidemiological study can be performed by general practitioners and has advantages over the more usual method of enquiry by telephone. Dyspepsia exerts an unusually high degree of stress and results in considerable demands on medical facilities.

Adolescent↗
PubMed1999

Performance, patient acceptance, appropriateness of indications and potential influence on outcome of EUS: a prospective study in 397 consecutive patients.

BACKGROUND: Although there is a large body of data on the accuracy of endoscopic ultrasonography (EUS) in the diagnosis and staging of various gastroenterological disorders, little has been published on the influence of EUS in the management of patients. Data on the performance of EUS and patient acceptance are also sparse. METHODS: During a 10-month period, all consecutive EUS examinations were categorized by the examiner according to the appropriateness of the indications. Prior examinations, performance of EUS (duration, premedication, complications), and patient acceptance (assessed using a questionnaire by an independent investigator) were recorded. A mean of 2 months after the procedure, referring physicians were asked about the extent to which the EUS results had influenced their further diagnostic and therapeutic approach. RESULTS: A total of 397 patients were included; they were referred for EUS after a mean of 1. 8 specific tests had been performed. The appropriateness of the indications for EUS was categorized as "classic," "useful," and "potentially useful" (categories 1 to 3) in 81% of cases. The referring physicians replied that EUS had provided useful additional information in 55% of cases; the EUS findings prompted further tests in 22% and made further examinations unnecessary in 30%. A change in therapy was believed to be directly due to EUS in only 6% of cases. The duration of the EUS examinations ranged from a mean of 8.1 minutes (esophageal indications) to 18.9 minutes (biliary indications). There were no complications. In patients who were able to remember the EUS examination (42%), 90% found it tolerable, and 83% of all the patients interviewed were willing to have the examination repeated with the same level of sedation. CONCLUSIONS: EUS is a safe examination that can be carried out within a reasonable time frame by experienced examiners and without significant patient discomfort when performed under conscious sedation. With regard to patient management, EUS mainly influences further diagnostic tests.

Adolescent↗
PubMed1999

Esophageal pharmacology and treatment of primary motility disorders.

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.

Animals↗
PubMed1999

Long-term results of endoscopic and percutaneous transhepatic treatment of benign biliary strictures.

BACKGROUND AND STUDY AIMS: Benign biliary strictures, mostly associated with biliary surgery, are of growing importance for the therapeutic endoscopist. In the short term, endoscopic therapy has success rates similar to those of surgery. With regard to the long-term results, fewer data are available, particularly concerning forms of treatment including percutaneous transhepatic biliary drainage (PTBD) as an additional tool. The present study was aimed at allowing evaluation of the short and long-term results of endoscopic and percutaneous treatment in patients with benign biliary strictures. PATIENTS AND METHODS: The charts of 40 consecutive patients treated during the period 1992-1994 (12 men, 28 women; median age 60.5 years, range 24-86) were analyzed retrospectively. Long-term follow-up was carried out by direct contact. In almost all of the cases, the endoscopic treatment consisted of papillotomy and stenting (single stent treatment 10 or 11.5 Fr); Yamakawa-type prostheses (14 or 16 Fr) were used in the PTBD patients. RESULTS: The primary treatment was successful in 37 of the 40 patients, including nine of 21 patients (43 %) treated endoscopically and 28 of 31 patients (90%) treated using the percutaneous approach. The complication rates after endoscopic retrograde cholangiopancreatography (ERCP) were 14%, compared with 26% after PTBD. Relief of the stricture was achieved in 25 patients after a median period of stent treatment of nine months (range 3-44), while recurrences were seen in six patients with stents in place for only 4.5 months (range 1-8), and in one patient with a metal stent. Therapy failed in two patients, and three were lost to follow-up. Serious long-term complications were rare, but there was a fatal complication in one patient with metal stents. The follow-up period was 44 months (range 11-66). Three patients underwent successful primary surgery, and three more underwent successful surgery after stricture recurrence; all were free of complaints after 49 months (range 40-44). CONCLUSIONS: Endoscopic and percutaneous treatment of benign biliary strictures is not only a short-term treatment, but also an adequate long-term therapeutic alternative to surgery, with tolerable complication rates. The period of stenting appears to influence the outcome, and the diameter of the stents used also probably plays a role. Prospective studies are required for further evaluation of these observations.

Adult↗
PubMed1999

NO releases bombesin-like immunoreactivity from enteric synaptosomes by cross-activation of protein kinase A.

The effect of nitric oxide (NO) on the release of bombesin-like immunoreactivity (BLI) was examined in synaptosomes of rat small intestine. The NO donor S-nitroso-N-acetylpenicillamine (SNAP; 10(-7) to 10(-4) M) significantly stimulated BLI release. In the presence of the NO scavenger oxyhemoglobin (10(-3) M) or the guanylate cyclase inhibitor ODQ (10(-5) M), SNAP-induced BLI release was antagonized. In addition, SNAP increased the synaptosomal cGMP content and elevation of cGMP levels by zaprinast (3 x 10(-5) M), an inhibitor of the cGMP-specific phosphodiesterase (PDE) type 5, and increased basal and SNAP-induced BLI release. NO-induced BLI release was blocked by Rp-adenosine 3',5'-cyclic monophosphorothioate (3 x 10(-5) M and 10(-4) M), an inhibitor of the cAMP-dependent protein kinase A, whereas KT-5823 (3 x 10(-6) M) and Rp-8-(4-chlorophenylthio)-cGMP (5 x 10(-5) M), inhibitors of the cGMP-dependent protein kinase G, had no effect. Because cGMP inhibits the cAMP-specific PDE3, thereby increasing cAMP levels, the role of PDE3 was investigated. Trequinsin (10(-8) M), a specific blocker of PDE3, stimulated basal BLI release but had no additive effect on NO-induced release, suggesting a similar mechanism of action. These data demonstrate that because of a cross-activation of cAMP-dependent protein kinase A by endogenous cGMP BLI can be released by NO from enteric synaptosomes.

Animals↗