Role of Helicobacter pylori in reflux esophagitis

It is now widely accepted that peptic ulcer disease (PUD) is a result of chronic infection of Helicobacter pylori (H. pylori). Thus, treatment of PUD should be aimed toward eradication of H. pylori with antibiotics. One the other hand, recent study from England suggested that eradication of H. pylori may provoke development of reflux esophagitis in duodenal ulcer patients. Despite duodenall ulcer patients with concomitant esophagitis is a specific type of esophagitis, it is important to recognize the development of reflux esophagitis after cure of H. pylori infection. Whether the development of reflux esophagitis is occurred in other H. pylori-related disease such as gastric ulcer remains to be studied.     

Roxatidine acetate in therapy of reflux esophagitis

A total of 3409 patients with gastro-oesophageal reflux disease were treated with roxatidine acetate. 60.7% of the patients received a daily dose of 2 x 75 mg roxatidine acetate, and the median duration of treatment was 5 weeks. Symptoms improved in about 90% of patients. For 1687 patients, endoscopic findings were available at the beginning and end of the treatment period. The overall endoscopic healing rate was 65.3%, and, depending on the initial finding (if), decreased from 92.9% (if: Savary-Miller stage I) to 67.5% (if: stage II), 40.7% (if: stage III), and to 22.5% (if: stage IV). Twenty-one patients experienced adverse events during the course of treatment, which, however, were either only minor or not related to the use of roxatidine acetate.     

Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis

Gene expression in the pharyngeal muscles of Caenorhabditis elegans is controlled in part by organ-specific signals, which in the myo-2 gene target a short DNA sequence termed the C subelement. To identify genes contributing to these signals, we performed a yeast one-hybrid screen for cDNAs encoding factors that bind the C subelement. One clone recovered was from daf-3, which encodes a Smad most closely related to vertebrate Smad4. We demonstrated that DAF-3 binds C subelement DNA directly and specifically using gel mobility shift and DNase1 protection assays. Mutation of any base in the sequence GTCTG interfered with binding in the gel mobility shift assay, demonstrating that this pentanucleotide is a core recognition sequence for DAF-3 binding. daf-3 is known to promote formation of dauer larvae and this activity is negatively regulated by TGFbeta-like signaling. To determine how daf-3 affects C subelement enhancer activity in vivo, we examined expression a gfp reporter controlled by a concatenated C subelement oligonucleotide in daf-3 mutants and other mutants affecting the TGFbeta-like signaling pathway controlling dauer formation. Our results demonstrate that wild-type daf-3 can repress C subelement enhancer activity during larval development and, like its dauer-promoting activity, daf-3's repressor activity is negatively regulated by TGFbeta-like signaling. We have examined expression of this gfp reporter in dauer larvae and have observed no daf-3-dependent repression of C activity. These results suggest daf-3 directly regulates pharyngeal gene expression during non-dauer development.     

The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease

Disorders of autonomic regulation are common in patients with Parkinson's disease (PD). Patients most frequently complain of dysphagia and therapy resistant constipation, as far as the gastrointestinal tract is concerned. These symptoms have to be attributed to a neuronal degeneration. In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride. 11 women and 13 men were examined, the average age was 67.3 years, the Webster rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to the limit, both with and without therapy. The other 22 patients showed an acceleration in transit on response to cisapride. On average the colonic transit of 130 hours was reduced to 79 hours. This objective improvement was associated with a subjective improvement. Central side effects or a worsening of Parkinsonian symptoms were not found. We conclude that cisapride is effective in the treatment of constipation in idiopathic PD.     

Recent topics in the medical treatment of reflux esophagitis

Reflux esophagitis is one of the most common disorders of the upper gastrointestinal tract. It can lead to obstruction through stricture formation, in more severe form to bleeding through ulceration, and to cancer development through the association of Barrett's esophagus. The vast majority of esophagitis can be managed medically. Medical management is separated into two categories: (1) life style modification and (2) drug therapy. Drug therapy includes antacids, prokinetics, sucralfate, H2 receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs). Among these, antisecretory therapy is the mainstay for the treatment. PPIs are shown to be superior to H2-RAs in healing of esophagitis and symptom relief. Recurrence, particularly of erosive esophagitis, is common without maintenance therapy. PPIs are also consistently superior to H2-RAs in maintenance of esophagitis healing. Interestingly, a recent report has suggested that curing Helicobacter pylori infection may provoke reflux esophagitis, raising the possibility that the gastroesophageal reflux diseases become more common in the future. Therefore, treatment strategy for reflux esophagitis needs to be re-established in terms of the future cost-effectiveness evaluation and quality-of-life assessments.     

The hypotensive effect of cisapride in rat

1. Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The aim of the present study was to investigate the effect of cisapride on blood pressure and the effects of muscarinic receptor antagonists on the cisapride-induced blood pressure changes. 2. Cisapride was given i.v. alone or 10 min after muscarinic receptor antagonists. Cisapride given i.v. produced a significant decrease in blood pressure in a dose-related manner. Atropine, AF-DX 116 and 4-DAMP given 10 min before cisapride injection, partially inhibited the hypotensive response to cisapride. In pithed rat, the effect of cisapride on blood pressure remained unaltered. 3. This study indicates that the action of cisapride is not through central mechanisms and part of cisapride's effect is through the cholinergic system.     

Biliary reflux can be a contributory cause of esophagitis

In recent years duodenogastric reflux has been recognised as a possible cause of oesophagitis. Alone or in combination, bile salts, trypsin, pepsin, and hydrochloric acid have all been shown to cause oesophagitis. Duodenal content in the oesophagus can be measured by means of a new fibre-optic sensor, Bilitech 2000, a device measuring the occurrence of bilirubin and yielding 24-hour readings from the distal oesophagus. Studies in which the device has been used have shown oesophageal bilirubin to be increased in patients with oesophagitis, especially in the subgroup with such complications as oesophageal stricture or ulceration, or Barrett's oesophagus. The evidence suggests that unsatisfactory response to proton pump inhibitors in reflux patients might be due to an increase in duodenal reflux, and should be treated surgically with fundoplication or biliary diversion. This may also be true of oesophagitis patients with complications, though this remains to be shown in clinical studies.     

Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride

BACKGROUND: Few studies have specifically addressed the management of the symptoms of gastro-oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents. METHODS: Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro-oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double-blind, double-dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated. RESULTS: At 4 weeks, heartburn was resolved in 65% (95% CI: 57-73%), 56% (48-64%) and 41% (32%-49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride (P < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups (P = 0.002). CONCLUSIONS: Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life.     

Esophagoprotective potential of cisapride. An additional benefit for gastroesophageal reflux disease

BACKGROUND: Synchronous bilateral breast carcinoma (SBBC) is an uncommon presentation, and the management of patients with this disease is not well established. METHODS: In order to evaluate whether patients with early-stage SBBC could be safely and effectively treated with bilateral breast-conserving therapy (BCT), the authors retrospectively reviewed the records of 24 patients with clinical Stage I-II SBBC treated during the period 1977-1989 with bilateral BCT. SBBC was defined as bilateral invasive carcinomas diagnosed no more than 1 month apart. The median age at diagnosis was 56 years (range, 32-85 years), and the median follow-up for surviving patients was 95 months (range, 68-157 months). Pathology slides were available for review in 19 cases. Cosmetic results and complications after BCT were scored. Outcome was compared with that of 1314 patients with unilateral Stage I or II breast carcinoma, within the same age range, treated during the same time period. RESULTS: There were no significant differences between the SBBC and unilateral groups in actuarial disease free survival (70% and 74%, respectively, at 5 years), overall survival (88% and 87%, respectively, at 5 years), or crude distribution of sites of first failure. Multivariate analysis of overall survival and disease free survival also did not show bilaterality to be a significant factor. The cosmetic results for the SBBC group were not significantly different from those for the unilateral group. Physician assessment of cosmetic outcome was excellent in 57% and good in 43% of SBBC patients evaluated 25-48 months after BCT. Long term complications were rare in both groups. CONCLUSIONS: Patients with early-stage SBBC can be safely treated with carefully planned, bilateral BCT, with outcome that appears to be comparable to that of patients with early-stage unilateral breast carcinoma.     

Addition of cisapride shortens colonoscopy preparation with lavage in elderly patients

The major envelope protein, p35, of vaccinia virus (VV; strain LIVP) was purified by extraction from virions with the non-ionic detergent Nonidet P-40. The protein was cleaved with CNBr. Four homogeneous peptides were isolated and their N-terminal amino-acid (aa) sequences determined. A computer search of a protein sequence databank revealed complete identity of the determined sequences with aa 44-63, 144-149, 154-165 and 224-238 of ORF H3 of the HindIII-H fragment of the VV genome [Rosel et al., J. Virol. 60 (1989) 436-446]. Earlier, Gordon et al. [Virology 167 (1988) 361-369] determined that the p35 surface protein of VV strain IHD-W is encoded by the H6 gene. Muravlev et al. [Biopolymery i kletka 6 (1990) 83-89 (Russian)] deduced from their data that gene A2 encodes this prominent antigen. Taking into account this ambiguity, we cloned the genes H3, H6 and A2 in expression vectors, prepared the specific antisera against the expression products and conducted the immunochemical analysis of the recombinant and native VV-specific proteins. It has been established that the H6 codes for an early protein that is found only in the infected cell extracts, but is absent in mature virions. The immunodominant protein p35 of VV strain LIVP is encoded by the gene H3. The gene A2 protein product is present mainly in the infected cell extract, but the antiserum against the A2 product shows a rather weak interaction with the 35-kDa fraction of structural VV proteins resolved by electrophoresis.     

Nissen fundoplication for reflux esophagitis. Long-term clinical and endoscopic results in 109 of 127 consecutive patients

OBJECTIVE: This study evaluates the clinical and endoscopic long-term results of Nissen fundoplication in reflux esophagitis. SUMMARY BACKGROUND DATA: Nissen fundoplication has been reported to give good results in the treatment of gastroesophageal reflux with success rates up to 78-97%. Most of the previous studies on long-term results of fundoplication have, however, been based on interviews with only sporadic endoscopic examinations. METHODS: Of 127 patients consecutively treated with Nissen fundoplication for reflux esophagitis, 109 were available for follow-up after a median of 77 months. Upper gastrointestinal endoscopy was done in 105 cases, and all the patients with reflux symptoms or abnormal endoscopic observations were referred to esophageal 24-hour pH monitoring and manometry. RESULTS: No symptoms of gastroesophageal reflux were reported by 73 of the 109 patients, but dysphagia was present in 47. Endoscopy showed defective fundic wrap in 24 patients. Objective evidence of reflux was found in 24 patients (endoscopic esophagitis in 18 and pathologic 24-hour pH score without esophagitis in 6). Esophagitis was found in 14 of the 24 patients with defective wrap, but in only 4 of the 81 with infact wrap. CONCLUSIONS: Nissen fundoplication alleviated symptoms of gastroesophageal reflux and cured esophagitis in great majority of cases. The main determinant of outcome was the state of the fundic wrap.     

The effect of nasal CPAP on nocturnal reflux in patients with aperistaltic esophagus

It has been shown that nasal continuous positive airway pressure (nasal CPAP) significantly reduces nocturnal reflux both in patients with sleep apnea and in patients without sleep apnea but consistent abnormal nocturnal reflux. The mechanism by which CPAP is thought to reduce reflux includes the elevation of the resting lower esophageal sphincter (LES) pressure. In this study, we tested the effect of nasal CPAP in two groups of patients with aperistaltic esophagus but with different resting LES pressure. Seven patients with scleroderma esophagus and six patients treated for achalasia were tested over a 48-h period. On the first night, the patients were untreated; on the second night, both groups received applied nasal CPAP at 8 cm H2O pressure. The percentage of time the pH < 4.0, the number of reflux events > 5 min, and the length of the longest reflux event were all significantly reduced in the patients with achalasia (p < 0.03), but not in the scleroderma group (p > 0.20). These results suggest that a residual resting LES pressure greater than that demonstrated by patients with scleroderma (> 10 mm Hg) may be necessary for nasal CPAP to affect nocturnal reflux.     

A placebo-controlled dose-ranging study of lansoprazole in the management of reflux esophagitis

Various signal processing techniques have been proposed to improve spectral estimation of closely spaced sinusoids in the presence of noise. This paper exploits frequency prior knowledge information to extract single peaks in magnetic resonance spectra, corresponding to metabolites of interest, by means of a highly selective finite impulse response filter. Thereafter the estimation of the parameters of the peaks is carried out using a singular-value-decomposition-based method known as HTLS. The new technique improves the performance of fully automated magnetic resonance spectroscopy data quantification when frequency prior knowledge is available.     

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease

A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin ITRA and OH-ITRA, respectively, were 287 +/- 109 ng/ml and 629 +/- 227 ng/ml at day -1 and 378 +/- 147 ng/ml and 725 +/- 242 ng/ml at day +1. The maximum Cmin values were observed at day +3. Six patients at day -1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.     

A case of reflux esophagitis after eradication of Helicobacter pylori]

Ceruminous glands are modified sweat glands, confined to the skin lining of the cartilaginous part of the external auditory meatus. Tumours arising from these glands are extremely rare. Confusion exists regarding the nomenclature 'ceruminoma' and controversies prevail on the standard way of management. Treatment often involves a multidisciplinary approach, requiring reconstruction after extensive surgical resection. A case report of adenoid cystic carcinoma of ceruminous glands is presented along with discussion of the various pathological types and a review of management.     

Salivary immunoglobulin concentrations in patients with epilepsy treated with carbamazepine

Various anti-epileptic drugs may affect the immune system. An IgA-depressing effect of carbamazepine has been proposed, but only serum concentrations have been studied. IgA constitutes a small fraction of the serum immunoglobulins, while it is the predominating one in external secretions. In the present study the concentrations of IgA, IgG and IgM in unstimulated saliva were determined by single radial immunodiffusion in 34 patients with partial epilepsy, and being treated with carbamazepine alone. Median salivary IgA concentration in the patients was 208 x 10(-3) g/l, compared to 150 x 10(3) g/l in 41 healthy controls. Salivary IgG and IgM concentrations were also somewhat higher in the patients than in the controls, while the albumin concentrations were similar in the two groups. However, the differences in the immunoglobulin concentrations between patients and controls were not significant at a 5% level. There was no significant correlation between the concentrations of IgA in saliva and serum.