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Biomedical subjects

N B Vakil

Publications and source records attributed to N B Vakil.

At least 19 recordsLinked to original sources
PubMed2002

Review article: gastro-oesophageal reflux disease and Helicobacter pylori infection.

Gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection are common conditions that frequently coexist. Controversy continues regarding the role of H. pylori infection in GERD. The results of some studies suggest that eradication of H. pylori may increase the risk for developing GERD, and some experts have suggested that chronic H. pylori infection may be of benefit. This article reviews the data on H. pylori infection and GERD and its treatment.

Drug Therapy, Combination↗
PubMed2001

Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review.

BACKGROUND: While the effectiveness of upper endoscopy has been established for acute nonvariceal upper gastrointestinal tract hemorrhage, its optimal timing has not been clearly defined. Early endoscopy has been advocated for its ability to achieve prompt diagnosis, risk stratification, and therapeutic hemostasis. OBJECTIVE: To determine whether early vs delayed endoscopy improves patient and economic outcomes for all risk groups with nonvariceal upper gastrointestinal tract hemorrhage. METHODS: A systematic review of 3 computerized databases (MEDLINE, HEALTHSTAR, and Cochrane Database of Systematic Reviews) was performed along with hand searching of published abstracts to identify English-language citations from 1980 to 2000. RESULTS: Twenty-three studies met explicit inclusion criteria. The highest-quality study examining outcomes in low-risk patients found no significant complications at 1-month follow-up for any outpatients managed with early endoscopy. The largest randomized trial of high-risk patients showed no mortality benefit but a significant decrease in transfusion requirements with early endoscopy. Seven of the 8 studies examining the effect of early endoscopy on length of stay as a measure of resource utilization demonstrated a significant reduction compared with that of delayed endoscopy. However, most included studies were found to suffer from 1 or more potentially significant methodologic shortcomings. CONCLUSIONS: The overwhelming majority of existing data suggest that early endoscopy is safe and effective for all risk groups. The clinical and economic outcomes of early endoscopy should be confirmed in additional well-designed randomized controlled trials. Given the strength of the evidence, efforts to develop a more standardized and time-sensitive approach to acute nonvariceal upper gastrointestinal tract hemorrhage should be undertaken.

Endoscopy, Gastrointestinal↗
PubMed2001

The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety.

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. AIM: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. METHODS: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. RESULTS: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. CONCLUSIONS: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.

Administration, Oral↗
PubMed2001

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety.

OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.

Administration, Oral↗
PubMed2001

Safety and efficacy of long term esomeprazole therapy in patients with healed erosive oesophagitis.

OBJECTIVE: To evaluate the safety and tolerability of long term treatment with esomeprazole in patients with healed erosive oesophagitis, and to describe its efficacy in the maintenance of healing. DESIGN AND SETTING: US multicentre, noncomparative, nonblind study. PATIENTS AND PARTICIPANTS: 807 patients with endoscopically confirmed healed erosive oesophagitis. METHODS: Patients received esomeprazole 40 mg once daily for up to 12 months. Adverse events and clinical laboratory tests were assessed over the study period. Endoscopy was performed at the final visit of the antecedent healing trials and at months 6 and 12 of the current safety trial; gastric biopsies were obtained at the initial visit of the healing trials and at the end of the safety trial. RESULTS: 80.9% of patients completed 6 months of treatment; 76.6% completed 12 months of treatment. There were no serious drug-related adverse events. Diarrhoea, abdominal pain, flatulence, and headache were the only treatment-related adverse events reported by >3% of patients. Mean changes in laboratory measures were generally small and not clinically meaningful. Plasma gastrin levels increased, as expected, and reached a plateau after 3 months. No changes in gastric histological scores were noted in the majority of patients. Evaluation of gastric biopsies revealed an overall decline in chronic inflammation and atrophy. Intestinal metaplasia findings remained essentially unchanged. Life table estimates of maintenance of healing were 93.7% [95% confidence interval (CI) 92.0 to 95.5%] at 6 months and 89.4% (95% CI 87.0 to 91.7%) at 12 months. CONCLUSIONS: Daily treatment with esomeprazole 40 mg for up to 1 year in patients with healed erosive oesophagitis was generally well tolerated and effective. No safety concerns arose.

Adolescent↗
PubMed2001

Debating the role of Helicobacter pylori infection.

Discussion continues on the role of Helicobacter pylori. The following debate provides a venue to examine 2 sides of this complicated issue. Dr. Vakil presents evidence that the eradication of H pylori will improve patients' health, while Dr. Go introduces evidence that suggests the presence of H pylori can be beneficial in particular cases. These clinicians also discuss the issue of whether to test and treat for H pylori and the role of H pylori in patients with gastroesophageal reflux disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Evidence-based health care: making health policy and management decisions.

The paradigm for health care delivery in the United States continues to evolve. Patients and physicians are beginning to reject guidelines for treatment that are solely based on cost reduction and are not evidence based. Future managed care guidelines will rely on the best external clinical evidence about the value of any given therapeutic intervention combined with individual physician experience and patient choice. Managed care organizations will need to play a greater role in the development, evaluation, and incorporation of clinical trials into their strategies.

Clinical Trials as Topic↗
PubMed1999

Identification of a novel penicillin-binding protein from Helicobacter pylori.

The Helicobacter pylori genome encodes four penicillin-binding proteins (PBPs). PBPs 1, 2, and 3 exhibit similarities to known PBPs. The sequence of PBP 4 is unique in that it displays a novel combination of two highly conserved PBP motifs and an absence of a third motif. Expression of PBP 4, but not PBP 1, 2, or 3, is significantly increased during mid- to late-log-phase growth.

Amino Acid Sequence↗
PubMed1998

Helicobacter pylori containing only cytoplasmic urease is susceptible to acid.

Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal diseases, produces large amounts of urease as an essential colonization factor. We have demonstrated previously that urease is located within the cytoplasm and on the surface of H. pylori both in vivo and in stationary-phase culture. The purpose of the present study was to assess the relative contributions of cytoplasmic and surface-localized urease to the ability of H. pylori to survive exposure to acid in the presence of urea. Toward this end, we compared the acid resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to that of bacteria which possessed both cytoplasmic and surface-localized or extracellular urease. Bacteria with only cytoplasmic urease activity were generated by using freshly subcultured bacteria or by treating repeatedly subcultured H. pylori with flurofamide (1 microM), a potent, but poorly diffusible urease inhibitor. H. pylori with cytoplasmic and surface-located urease activity survived in an acid environment when 5 mM urea was present. In contrast, H. pylori with only cytoplasmic urease shows significantly reduced survival when exposed to acid in the presence of 5 mM urea. Similarly, Escherichia coli SE5000 expressing H. pylori urease and the Ni2+ transport protein NixA, which expresses cytoplasmic urease activity at levels similar to those in wild-type H. pylori, survived minimally when exposed to acid in the presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone is not sufficient (although cytoplasmic urease activity is likely to be necessary) to allow survival of H. pylori in acid; the activity of surface-localized urease is essential for resistance of H. pylori to acid under the assay conditions used. Therefore, the mechanism whereby urease becomes associated with the surface of H. pylori, which involves release of the enzyme from bacteria due to autolysis followed by adsorption of the enzyme to the surface of intact bacteria ("altruistic autolysis"), is essential for survival of H. pylori in an acid environment. The ability of H. pylori to survive exposure to low pH is likely to depend on a combination of both cytoplasmic and surface-associated urease activities.

Benzamides↗
PubMed1997

Localization of Helicobacter pylori urease and heat shock protein in human gastric biopsies.

Helicobacter pylori is a spiral, gram-negative bacterium which causes chronic gastritis and plays a critical role in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori expresses significant urease activity which is an essential virulence factor. Since a significant fraction of urease activity is located on the surface of the bacterium, the urease molecule is a logical choice as an antigen for a vaccine; currently recombinant urease apoenzyme is being tested as a vaccine in phase II clinical trials. We have recently demonstrated that urease and HspB (a homolog of the GroEL heat shock protein) become associated with the surface of H. pylori in vitro in a novel manner: these cytoplasmic proteins are released by bacterial autolysis and become adsorbed to the surface of intact bacteria, reflecting the unique characteristics of the outer membrane. To determine if similar mechanisms are operative in vivo, we determined the ultrastructural locations of urease and HspB within bacteria present in human gastric biopsies. Our results demonstrate that both urease and HspB are located within the cytoplasm of all bacteria examined in human gastric biopsies. Interestingly, a significant proportion of the bacteria examined also possessed variable amounts of surface-associated urease and HspB antigen (from 5 to 50% of the total antigenic material), indicating that in vivo, H. pylori has surface characteristics which enable it to adsorb cytoplasmic proteins. This is consistent with our altruistic autolysis model in which H. pylori uses genetically programmed bacterial autolysis to release urease and other cytoplasmic proteins which are subsequently adsorbed onto the surface of neighboring viable bacteria. These observations have important implications regarding pathogenesis and development of vaccines for H. pylori.

Bacterial Proteins↗
PubMed1997

Antibiotic-induced iatrogenic hemobilia.

A classical triad of clinical signs defines hemobilia: GI bleeding, right upper quadrant abdominal pain, and jaundice. Although there are a number of causes, it is largely described in conjunction with blunt or penetrating liver trauma and as an iatrogenic complication of therapeutic hepatobiliary interventions. We present a case of antibiotic-induced vitamin K deficiency that resulted in hemobilia complicating acalculous cholecystitis.

Aged↗
PubMed1996

Biliary cryptosporidiosis in HIV-infected people after the waterborne outbreak of cryptosporidiosis in Milwaukee.

BACKGROUND: In March 1993, the municipal water supply in Milwaukee became contaminated with cryptosporidium and a widespread outbreak of cryptosporidiosis occurred. METHODS: We retrospectively studied the relations among the clinical presentation, CD4 count, and survival in a group of 82 patients infected with the human immunodeficiency virus (HIV) in whom cryptosporidiosis developed during the outbreak. Infection was documented by the finding of cryptosporidium in stool. RESULTS: There was a sharp increase in the number of HIV-infected patients with cryptosporidiosis after the period of water contamination. Four of 24 patients with biliary symptoms (17 percent) and 30 of 58 without biliary symptoms (52 percent) were alive one year after the outbreak (P = 0.003). Twenty-one of the patients with biliary symptoms had CD4 counts < or = 50 per cubic millimeter, as compared with 36 of 57 patients without biliary symptoms (88 percent vs. 63 percent, P = 0.03). The CD4 count was not available for one patient in the latter group. Within one year, 41 of the patients with CD4 counts < or = 50 per cubic millimeter had died, as compared with 6 of those with higher counts (72 percent vs. 25 percent, P < 0.001). After adjustment for the CD4 count, independent predictors of death were older age and the presence of nausea and vomiting. CONCLUSIONS: When HIV-infected patients are exposed to cryptosporidium, those with CD4 counts < or = 50 per cubic millimeter are at increased risk for biliary symptoms and for death within one year after the infection.

AIDS-Related Opportunistic Infections↗
PubMed1989

Absence of an upper esophageal sphincter response to acid reflux.

Manometric studies of the upper esophageal sphincter (UES) were done on 17 volunteer subjects and 16 patients with endoscopically evident esophagitis. Subjects entered one or both of two protocols designed to assess the effect of esophageal acid exposure on UES pressure. In protocol 1, continuous 3-h postprandial recordings were obtained; a modified sleeve sensor was used to measure UES pressure, and an intraluminal pH electrode was used to detect occurrences of spontaneous gastroesophageal acid reflux. In protocol 2, UES pressure was continuously monitored during a 10-min control period, followed by a 25-min period of esophageal perfusion with 0.1 N HCl. Our findings were that: 1) basal UES pressure measured during the 3-h recording was similar in the normal volunteers and in the group of patients with esophagitis, 2) episodes of spontaneous gastroesophageal acid reflux were not associated with a change in UES pressure in either the normal volunteers or in the patients with esophagitis, and 3) esophageal perfusion with HCl did not affect the UES pressure in either group, although severe heartburn occurred in most of the esophagitis patients. We conclude that the upper esophageal sphincter exhibits normal basal pressure in patients with esophagitis and that esophageal acid exposure, either spontaneous or experimental, does not affect UES pressure in normal volunteers or in patients with esophagitis.

Adult↗
PubMed1989

The benefit of head rotation on pharyngoesophageal dysphagia.

This study examined the effect of head rotation on the mechanics of swallowing in healthy subjects, as well as the effects of this postural change on the oropharyngeal swallow of five patients with lateral medullary syndrome (LMS). Videofluoroscopic studies of swallowing in the normal subjects revealed that head rotation to either side increased upper esophageal sphincter (UES) opening diameter by an average of 2mm without affecting the period of UES opening or the oropharyngeal transit time. Maximal rotation of the head to the right or left caused the bolus to lateralize away from the direction of rotation, and also caused a significant (18mmHg or 35%) fall in UES pressure. In the face forward position, the LMS patients exhibited barium residue in the pharynx and pyriform sinuses, as well as diminished UES opening diameter. The fraction of the bolus swallowed and the UES opening diameter increased significantly with the head turned toward the paretic side in the LMS patients. We conclude that head rotation can improve swallowing in patients with unilateral oropharyngeal dysphagia. Two potentially beneficial effects were observed: (1) functional exclusion of the relatively flaccid, weakened pharyngeal wall, and (2) reduced UES tone. Which of these mechanisms is operative probably depends on the dominant mechanisms of dysphagia. In individuals with substantial impairment of UES opening, head turning reduces the resistance of the sphincter that must be overcome by pharyngeal contraction. In individuals with a flaccid hemipharynx, which dissipates pharyngeal pressure, head rotation excludes these structures from the bolus path and allows pharyngeal pressure to be directed at the UES.

Adult↗
PubMed1988

Emergencies of the biliary tract.

The traditional approach to urgent therapy of biliary tract disease has undergone significant change. Technologic advances now permit a nonoperative approach to acute cholangitis, acute gallstone pancreatitis and hemobilia. Acute cholecystitis continues to be treated surgically in most cases. The clinical use of such nonoperative therapy has been guided mainly by retrospective data. The precise indications and optimal timing for endoscopic and radiologic therapy and their relationship to traditional surgical therapy remains to be defined by careful prospective evaluation.

Acute Disease↗