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Biomedical subjects

M F Vaezi

Publications and source records attributed to M F Vaezi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Current therapies for achalasia: comparison and efficacy.

Achalasia is a primary esophageal motor disorder of unknown etiology producing complaints of dysphagia, regurgitation, and chest pain. The current treatments for achalasia involve the reduction of lower esophageal sphincter (LES) pressure resulting in improved esophageal emptying. Calcium channel blockers and nitrates, once used as initial treatment strategy for early achalasia, are now only used in patients who are not candidates for pneumatic dilation or surgery and those not responding to botulinum toxin injections. By virtue of the more rigid balloons, the current pneumatic dilators are more effective and have better efficacy than the older more compliant balloons. The graded approach to pneumatic dilation using the Rigiflex balloons (3.0, 3.5, and 4.0 cm) are now the most commonly used nonsurgical means of treating patients with achalasia, resulting in symptom improvement in up to 90% of patients. Surgical myotomy, once with high morbidity and long hospital stay, can now be performed laparoscopically with similar efficacy to the open surgical approach (94% vs. 84%, respectively), reduced morbidity, and hospitalization time. Given the advances in both balloon dilation and laparoscopic myotomy, most patients with achalasia can now choose between these two equally efficacious treatment options. Botulinum toxin injection of the LES should be reserved for patients who cannot undergo balloon dilation and are not surgical candidates.

Algorithms↗
PubMed1998

Helicobacter pylori and gastroesophageal reflux disease: the bug may not be all bad.

Peptic ulcer disease and gastric cancer of the antrum and body have been declining in the 20th century. In contrast, a new group of diseases are increasingly rapidly in Western countries: gastroesophageal reflux disease, Barrett's esophagus, and adenocarcinoma of the distal esophagus. Recent studies suggest this phenomenon may be related to the simultaneous fall in the prevalence of Helicobacter pylori (H. pylori) colonization, especially by the virulent cagA + strains. H. pylori infection with the cagA+ strain is potentially protective against the spectrum of gastroesophageal reflux disease because it lowers intragastric acidity as the result of a pangastritis, frequently with multifocal gastric atrophy and possibly increased intragastric ammonia production. Assuming that some types of H. pylori strains are protective, our entire approach to the worldwide elimination of this organism, sometimes indiscriminately, will need critical reevaluation.

Adenocarcinoma↗
PubMed1997

Bile reflux in columnar-lined esophagus.

Barrett's esophagus represents a metaplastic process in which the normal squamous epithelium of the lower esophagus is replaced by metaplastic columnar epithelium. Although the role of acid and pepsin in the development of Barrett's esophagus is well accepted, the importance of duodenogastroesophageal reflux in this disorder is not clear.

Barrett Esophagus↗
PubMed1997

Twenty-four-hour ambulatory esophageal pH monitoring in the diagnosis of acid reflux-related chronic cough.

To define the role of ambulatory pH monitoring in evaluating chronic cough, we studied esophageal pH values of patients referred to a gastroenterology laboratory. Chronic cough was evaluated in 31 patients, who were grouped based on response to treatments; 11 patients (35.5%) had gastroesophageal reflux (GER)-related cough, 11 (35.5%) had pulmonary/otorhinolaryngologic-related cough (1 bronchitis, 6 asthma, 2 postnasal drip, 1 pneumonia), and 9 patients (29%) had cough of unknown etiology. Esophageal pH values of groups were compared. Excessive acid reflux distally (upright and supine) and proximally (upright) and cough symptom frequency related to acid reflux were significantly higher in patients with GER. Esophageal pH monitoring had good sensitivity (91%), specificity (82%), and positive (83%) and negative (90%) predictive values in identifying GER-related cough. In summary, ambulatory pH monitoring is an excellent test for identifying patients with GER-related cough.

Adult↗
PubMed1997

Contribution of acid and duodenogastro-oesophageal reflux to oesophageal mucosal injury and symptoms in partial gastrectomy patients [see comment].

BACKGROUND: The role of acid and pepsin in causing symptoms and oesophagitis is well established; however, the significance of duodenogastro-oesophageal reflux (DGOR) in this disorder is unclear. AIMS: To understand the role of acid and DGOR in causing upper gastrointestinal (GI) symptoms and oesophageal mucosal injury in partial gastrectomy (PG) patients. METHODS: Thirty two PG patients with upper GI symptoms were studied. Twenty four hour ambulatory acid and bilirubin measurements were obtained with Bilitec 2000 using glass electrode and fibreoptic sensor. Upper GI symptoms and oesophagitis were correlated with either acid or DGOR. RESULTS: The PG patients were a heterogeneous group: 28% (9/32) had mixed reflux (acid+/DGOR+); 50% (16/32) had only DGOR (acid-/DGOR+); and 22% (7/32) had neither (acid-/DGOR-). Upper GI symptoms were associated with both mixed reflux (69%) and DGOR (24%). Six patients (67%) in the acid+/DGOR+ group had oesophagitis; no acid-/DGOR+ or acid-/DGOR- patients had oesophagitis. Mixed reflux showed a significant (p < 0.0001) association with oesophagitis, while DGOR did not (p = 0.3). CONCLUSIONS: (1) The majority of upper GI symptoms and all cases of oesophagitis in the PG patients occurred in patients who had mixed refluxate (acid and DGOR); (2) DGOR without simultaneous acid reflux may cause symptoms, but was not associated with oesophagitis in this patient group.

Analysis of Variance↗
PubMed1997

Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring.

OBJECTIVES: To assess the reproducibility and reliability of the proximal pH probe in detecting acid reflux into the proximal esophagus. METHODS: Using dual probe ambulatory esophageal pH monitoring, we studied 32 subjects (11 healthy control subjects, 10 patients with distal esophageal acid reflux, and 11 patients with both distal and proximal esophageal acid exposure) on two separate days within a 20-day period. The distal pH probe was placed 5 cm above the manometrically determined lower esophageal sphincter, and the proximal probe was positioned immediately distal to the upper esophageal sphincter. Patients were categorized on the basis of the esophageal pH data obtained during the first study. Reflux parameters assessed were the percentages of time in which pH was <4 in the total, upright, and supine positions. To be considered reproducible, all three of the above parameters had to remain in the same category as the first day's results. RESULTS: Intrasubject reproducibility of the proximal probe was 91-100% in healthy subjects, 70-90% in patients with distal esophageal acid reflux, and 45-73% in patients with proximal esophageal acid reflux. The proximal probe reproducibility for the overall diagnosis of gastroesophageal reflux disease was 91% in healthy subjects, 70% in patients with distal esophageal acid reflux, and only 55% in those with proximal esophageal acid reflux. Statistical analysis demonstrated only a fair index of concordance (kappa = 0.40) for the proximal probe. CONCLUSIONS: The proximal pH probe has excellent specificity (91%) but poorer sensitivity and reproducibility (55%) for identifying abnormal amounts of proximal esophageal acid reflux. Therefore, a negative test result does not exclude proximal reflux with microaspiration as a cause of atypical reflux symptoms.

Adult↗
PubMed1996

Conformationally defined 6-s-trans-retinoic acid analogs. 3. Structure-activity relationships for nuclear receptor binding, transcriptional activity, and cancer chemopreventive activity.

We recently demonstrated that conformationally defined 6-s-trans-retinoic acid (RA) analogs were effective in the prevention of skin papillomas (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) and selective agonists for nuclear receptor binding and activation (Alam et al. J. Med. Chem. 1995, 38, 2302-2310). In order to probe important structure-activity relationships, we evaluated a homologous series of four 6-s-trans-retinoids that are 8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different substituents at 2' (R2) and 3' (R1) positions on the cyclohexene ring. UAB1 (R1 = R2 = H), UAB4 (R1 = R2 = Me), UAB7 (R1 = Me, R2 = iPr), and UAB8 (R1 = Et, R2 = iPr) contain alkyl R groups that mimic, to different extents, portions of the trimethylcyclohexenyl ring of RA. Both 9Z- and all-E-isomers of these retinoids were evaluated in binding assays for cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), a nuclear retinoic acid receptor (RAR alpha), and a nuclear retinoid X receptor (RXR alpha). The all-E-isomers of UAB retinoids bound tightly to CRABPs and RAR alpha, the binding affinity of the all-E-isomer increased systematically from UAB1 to UAB8, and binding for the latter was comparable to that of all-E-RA. In contrast to RA, the (9Z)-UAB retinoids were at least 200-fold less active than the all-E-isomers in binding to RAR alpha. The (9Z)-UAB isomers exhibited increasingly stronger binding to RXR alpha, and (9Z)-UAB8 was nearly as effective as (9Z)-RA in binding affinity. The retinoids were also evaluated in gene expression assays mediated by RAR alpha and RXR alpha homodimers or RAR alpha/RXR alpha heterodimers. Consistent with the binding affinities, the (all-E)-UAB retinoids activated gene transciption mediated by RAR alpha homodimers or RAR alpha/RXR alpha heterodimers, while the (9Z)-UAB isomers activated only the RXR alpha homodimer-mediated transcription. The all-E- and 9Z-isomers of the UAB retinoids were further evaluated for their capacity to prevent the induction of mouse skin papillomas. When compared to RA, only the (all-E)-UAB retinoids containing bulky R1 and R2 groups were effective in this chemoprevention assay. (9Z)-RA displayed equal capacity as RA to prevent papillomas, while the 9Z-isomers of the UAB retinoids were much less effective. Taken together, these studies demonstrate that the cyclohexenyl ring substituents of 6-s-trans-UAB retinoids are important for their biological activities and that the chemopreventive effect of the all-E-isomers of these retinoids correlates well with their capacity to bind to RARs and activate RAR/RXR-mediated transcription.

Animals↗
PubMed1996

Placebo-controlled trial of cisapride in postgastrectomy patients with duodenogastroesophageal reflux.

Medical treatment of duodenogastroesophageal reflux in postgastrectomy patients has been disappointing. Using ambulatory esophageal bilirubin monitoring, we evaluated the efficacy of cisapride in this disorder. Ten chronically symptomatic partial gastrectomy patients (5 Billroth I, 5 Billroth II; 8 men; average age 57) with duodenogastroesophageal reflux were randomized to four weeks of either placebo or cisapride (20 mg four times a day) in a double-blind crossover study. Significantly improved patients continued to take cisapride for an additional four months. Duodenogastroesophageal reflux was assessed at baseline and after four weeks on each therapy. Daily diary recorded symptoms and mean monthly scores were determined. Global symptom improvements were assessed at the end of each treatment period. Compared to placebo, cisapride significantly (P < 0.05) decreased duodenogastroesophageal reflux. Overall symptom improvements were assessed at the end of each treatment period. Compared to placebo, cisapride significantly (P < 0.05) decreased duodenogastroesophageal reflux. Overall symptoms improved in 70% of patients on cisapride compared to 10% on placebo (P < 0.01). Mean monthly scores significantly (P < 0.05) improved for abdominal pain, regurgitation, and belching. These symptoms remained improved after four months of chronic therapy. We conclude that cisapride significantly reduces duodenogastroesophageal reflux and results in short- and long-term symptom improvements in postgastrectomy patients and that cisapride offers the first successful medical therapy for duodenogastroesophageal reflux in postgastrectomy patients.

Anti-Ulcer Agents↗
PubMed1996

Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease.

BACKGROUND & AIMS: Acid and pepsin are known to cause esophagitis. However, the role of duodenogastroesophageal reflux (DGER) in producing esophageal mucosal injury across the spectrum of gastroesophageal reflux disease (GERD) is controversial. METHODS: Twenty controls (13 men; mean age, 41 years), 30 patients with GERD (15 men; mean age, 41 years), and 20 patients with Barrett's esophagus (17 men; mean age, 58 years) were studied. Twenty-four-hour ambulatory acid and bilirubin measurements were obtained with Bilitec 2000 using a glass pH electrode and fiberoptic sensor. RESULTS: Percentage times pH was < 4, bilirubin level was > or = 0.14, and fasting gastric bile acid concentrations showed a graded increase across the GERD spectrum. Esophageal exposure to both acid and DGER was the most prevalent reflux pattern (100% in patients with complicated and 89% in patients with uncomplicated Barrett's esophagus, 79% in patients with esophagitis, and 50% in patients without esophagitis). The majority (70%-91%) of DGER episodes occurred in an acidic environment (pH < 4). Linear regression analysis found a significant correlation (r = 0.73; P < 0.01) between percentage time pH was < 4 and percentage time bilirubin absorbance level was > or = 0.14. CONCLUSIONS: Both acid and DGER show a graded increase in severity across the GERD spectrum. Acid and DGER occur simultaneously in the majority of the reflux episodes.

Adult↗
PubMed1996

An ambulatory bilirubin monitoring device for duodenogastroesophageal reflux.

Reflux of duodenal contents into the stomach is a normal physiological event occurring most commonly at night' but also in the fasting and postprandial daytime periods.' Previously, the terms "bile reflux" and "alkaline reflux" have been used to describe this process. However, duodenal contents contain more than just "bile" and studies have shown that the term "alkaline reflux" is a misnomer since pH > 7 does not correlate with reflux of duodenal contents.' Therefore, duodenogastroesophageal reflux (DGER) may be a more appropriate term to describe the pathological regurgitation of duodenal contents through the pylorus into the stomach with subsequent reflux into the esophagus.

Journal Article↗
PubMed1995

Dental erosion and acid reflux disease.

OBJECTIVE: To determine the relation between gastroesophageal reflux disease and dental erosion using ambulatory 24-hour esophageal pH testing. DESIGN: Cross-sectional observational study. SETTING: Tertiary referral center. PATIENTS: The dental group consisted of 12 patients with idiopathic dental erosion who were identified by dentists and screened for gastroesophageal reflux disease using 24-hour pH testing. The gastroenterology group consisted of 30 patients who had 24-hour pH testing in the esophageal laboratory and who were referred for dental evaluation (10 did not have reflux, 10 had distal reflux, and 10 had proximal reflux). MEASUREMENTS: 24-hour esophageal pH monitoring using a pH probe in the distal and proximal esophagus. Complete dental examination with particular attention to the presence and severity of dental erosion; plaque; gingival damage; and decayed, missing, and filled teeth. Analysis of saliva for pH, flow rates, buffering capacity, and calcium and phosphorus levels. Standardized questionnaire to ascertain possible causes of dental erosion and presence of reflux symptoms. RESULTS: Ten of the 12 patients in the dental group (83% [95% CI, 52% to 98%]) had gastroesophageal reflux on esophageal pH monitoring. Nine had distal and 7 had proximal reflux. Seven had reflux in the upright position only, 1 had reflux in the supine position only, and 2 had both upright and supine reflux. No saliva abnormalities were found. Ten patients had typical symptoms of gastroesophageal reflux, but dietary or mechanical problems that may have been causing dental erosion were not identified. In the gastroenterology group, upright reflux was seen in 5 of the 10 patients with distal reflux and in all 10 patients with proximal reflux. In addition, 40% of patients in the gastroenterology group (12 of 30) had dental erosion (4 of the 10 with distal reflux [40%], 7 of the 10 with proximal reflux [70%], and only 1 of the 10 without reflux [10%]; P = 0.02 for those with reflux compared with those without reflux). The cumulative dental erosion score correlated with proximal upright reflux when all 24 study patients with erosion were analyzed (r = 0.55 [P < 0.01]); this correlation was even stronger in the subgroup of 12 patients with abnormal amounts of proximal upright reflux (r = 0.84 [P = 0.001]). CONCLUSION: Dental erosion is a common finding in patients with gastroesophageal reflux disease and should be considered an atypical manifestation of this disease.

Cross-Sectional Studies↗
PubMed1995

Role of acid and duodenogastric reflux in esophageal mucosal injury: a review of animal and human studies.

The role of acid and duodenogastric reflux (DGR) in the development of esophageal mucosal injury has been extensively investigated using both animal and human models. In this report, clinical and experimental data are reviewed. The mechanisms by which gastric and duodenal contents produce esophageal mucosal injury are also discussed. Acid and pepsin are unquestionably important in causing mucosal damage at low pH values in both animal and human models. Animal models suggest synergistic damaging potential for conjugated bile acids and HCI as well as that of unconjugated bile acids and trypsin in more neutral pH values. Human evidence for the involvement of bile and its constituents has been controversial; however, the advent of better technology to detect DGR is beginning to clarify the role of these constituents. The contribution of each methodology in clarifying the extent of involvement of DGR in esophageal mucosal injury is reviewed. Despite some conflicting results, preliminary human studies support the results from the animal data suggesting synergistic damaging effects for both bile and acid in esophageal mucosal injury. The implication of these studies in treating gastroesophageal reflux disease are discussed.

Animals↗
PubMed1995

Synergism of acid and duodenogastroesophageal reflux in complicated Barrett's esophagus.

BACKGROUND: The role of acid and duodenogastroesophageal reflux (DGER) in the development of complications in Barrett's esophagus is controversial. We characterized the esophageal reflux constituents in patients with and without complications of Barrett's esophagus. METHODS: Using a new fiber-optic system we studied 12 normal subjects (six male; mean age, 46 years) and 20 patients with Barrett's esophagus (17 male; mean age, 58 years), nine with uncomplicated (seven male; mean age, 55 years) and 11 with complicated Barrett's esophagus (seven with stricture, two with ulcer, and two with dysplasia; 10 male; mean age, 61 years). Fasting gastric bile acid concentrations were measured. Twenty-four-hour ambulatory acid and bilirubin measurements were obtained with the fiber-optic system by using a glass electrode and fiber-optic sensor. The data were then analyzed for percent total time pH < 4 and > 7 and bilirubin absorbance > 0.14%. RESULTS: Percent times pH < 4, bilirubin absorbance > 0.14%, and fasting gastric bile acid concentrations were significantly greater in patients with complicated Barrett's esophagus compared with patients with uncomplicated Barrett's esophagus with both being higher than the controls. Acid reflux paralleled bile reflux in the two Barrett's esophagus groups (r = 0.44, p < 0.05), but percent time pH > 7 did not differentiate between the two groups. CONCLUSIONS: (1) Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus. (2) Complications in Barrett's esophagus may be due to synergism between acid and bile rather than either constituent alone.

Alkalies↗
PubMed1995

Transient protein S deficiency associated with cerebral venous thrombosis in active ulcerative colitis.

Cerebral venous thrombosis is an uncommon complication of ulcerative colitis. We report the case of a 29-yr-old female with a recent diagnosis of ulcerative colitis who suffered stroke secondary to thrombosis of the veins of Galen and straight sinus. A search for a hypercoagulable state revealed a nonfamilial transient protein S deficiency. Possible involvement of C4b-binding protein in this hypercoagulable state is discussed.

Acute Disease↗
PubMed1994

A conformationally defined 6-s-trans-retinoic acid isomer: synthesis, chemopreventive activity, and toxicity.

A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-configuration for the intermediate aldehyde. A Horners-Emmons condensation with this aldehyde then produced retinoic acid analogs with both 9Z- and 9Z,13Z-configurations. An I2-catalyzed isomerization of the intermediate 9Z-aldehyde yielded the all-E-aldehyde, which was olefinated as above to yield the (all-E)- and (13Z)-retinoic acid analogs of 1. Each configurational isomer of 1 was evaluated for its ability to inhibit the binding of retinoic acid to CRABP (chick skin) and to inhibit the chemical induction of ornithine decarboxylase in mouse skin. In each assay (all-E)-1 was the most active isomer, and this activity was comparable to or better than that for (all-E)-retinoic acid. (all-E)-1 and (13Z)-1 were both shown to be equally effective as (13Z)-retinoic acid in suppressing the proliferation of human sebaceous cells in vitro. (all-E)-1 was further evaluated for its ability to prevent the induction of mouse skin papillomas and to induce signs of vitamin A toxicity in mice. The cancer chemopreventive activity of (all-E)-1 was comparable to that of (all-E)-retinoic acid, and the toxicity was comparable to or slightly better than that of the natural vitamin.

3T3 Cells↗
PubMed1994

Duodenogastroesophageal reflux: relationship to pH and importance in Barrett's esophagus.

BACKGROUND/AIMS: Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. The purpose of this study was to understand better the relationship of pH (< 4 and > 7), duodenogastroesophageal reflux, and fasting bile acid concentrations in producing esophageal damage. METHODS: Using a spectrophotometric technique to measure bile reflux, four groups were studied: healthy subjects, reflux patients, patients with Barrett's esophagus, and patients with esophageal symptoms after partial gastrectomy. RESULTS: Simultaneous 24-hour pH and bile monitoring of distal esophagus found close association between total percent of time pH < 4 and duodenogastroesophageal reflux (r = 0.78; P < 0.001) but a poor relationship (r = -0.06) with total percent of time pH > 7, suggesting that the term alkaline reflux is a misnomer. Duodenogastroesophageal reflux increased significantly with the severity of reflux disease, being greatest in patients with Barrett's esophagus and comparable with that in patients with partial gastrectomy. Fasting bile acid concentrations did not distinguish patients with Barrett's esophagus from those with reflux. Rather, increased quantity of acid reflux was the single factor most characterizing patients with Barrett's esophagus. Omeprazole (20 mg twice daily) normalized acid reflux parameters (13.8% +/- 1.6% to 0.8% +/- 0.6%) and significantly (P < 0.001) decreased duodenogastroesophageal reflux (32.8% +/- 6.9% to 4.7% +/- 1.7%). CONCLUSIONS: Acid reflux is the primary factor in the development of Barrett's esophagus. Bile reflux parallels acid reflux and, at best, may have a synergistic role. Aggressive acid suppression with omeprazole markedly decreases both.

Acids↗
PubMed1994

Validation studies of Bilitec 2000: an ambulatory duodenogastric reflux monitoring system.

Bilitec 2000, a fiber-optic spectrophotometer, detects duodenogastric (DG) reflux in an ambulatory setting independent of pH by measuring bilirubin in bile. Studies were performed for independent validation and better understanding of limitations of this system. Bilitec and a conventional spectrophotometer were used to assess the effect of gastric acidity on the spectral absorbance of refluxed DG contents, employing bilirubin ditaurate (BDT) and human bile. Total bile acid concentrations correlated with Bilitec absorption. BDT and bile had hypsochromic shift (400 nm) in spectrophotometric maximum wavelength (lambda max; 450 nm) in an acidic environment (pH < 3.5), corresponding to an approximately 30% decrease in absorption measured by Bilitec. Bile acid concentrations correlated strongly with Bilitec absorption for all 63 samples (R = 0.82) with pH > 3.5 (n = 31, R = 0.81), but correlation was less strong for 32 samples with pH < 3.5 (R = 0.70). As currently designed, Bilitec adequately measures DG reflux but underestimates it by at least 30% in acidic medium (pH < 3.5). Design modifications are suggested for improving the sensitivity of this equipment.

Bile↗