Internists, Gastroenterologist (digestive)
33 years of experience

Accepting new patients
100 Ucla Medical Plz
Suite 303
Los Angeles, CA 90095
310-206-6279
Locations and availability (5)

Education ?

Medical School
McGill University Faculty Of Medicine (1977)
Foreign school

Awards & Distinctions ?

Appointments
Ronald Reagan Ucla Medical Center

Affiliations ?

Dr. Kovacs is affiliated with 5 hospitals.

Hospital Affilations

Score

Rankings

  • UCLA Medical Center
    10833 Le Conte Ave, Los Angeles, CA 90095
    • Currently 4 of 4 crosses
    Top 25%
  • Santa Monica - UCLA Medical Center
    1250 16th St, Santa Monica, CA 90404
    • Currently 3 of 4 crosses
    Top 50%
  • Veterans Affairs Greater Los Angeles Healthcare Center
    11301 Wilshire Blvd, Los Angeles, CA 90073
  • University of California - Ronald Reagan UCLA Medical Center
    757 Westwood Plz, Los Angeles, CA 90095
  • Mattel Chldns Hosp. At Ucla
    10833 Le Conte Ave, Los Angeles, CA 90095
  • Publications & Research

    Dr. Kovacs has contributed to 46 publications.
    Title Ischemic Colitis As a Cause of Severe Hematochezia: Risk Factors and Outcomes Compared with Other Colon Diagnoses.
    Date January 2012
    Journal Gastrointestinal Endoscopy
    Excerpt

    Risk factors and outcomes of severe hematochezia from ischemic colitis compared with other colonic diagnoses have not been well studied.

    Title Gastric Acid Inhibition in the Treatment of Peptic Ulcer Hemorrhage.
    Date February 2010
    Journal Current Gastroenterology Reports
    Excerpt

    Upper gastrointestinal bleeding from peptic ulcer disease is a common clinical event, resulting in considerable patient morbidity and significant health care costs. Inhibiting gastric acid secretion is a key component in improving clinical outcomes, including reducing rebleeding, transfusion requirements, and surgery. Raising intragastric pH promotes clot stability and reduces the influences of gastric acid and pepsin. Patients with high-risk stigmata for ulcer bleeding (arterial bleeding, nonbleeding visible vessels, and adherent clots) benefit significantly from and should receive high-dose intravenous proton pump inhibitors (PPIs) after successful endoscopic hemostasis. For patients with low-risk stigmata (flat spots or clean ulcer base), oral PPI therapy alone is sufficient. For oozing bleeding (an intermediate risk finding), successful endoscopic hemostasis and oral PPI are recommended. Using intravenous PPIs before endoscopy appears to reduce the frequency of finding high-risk stigmata on later endoscopy, but has not been shown to improve clinical outcomes. High-dose oral PPIs may be as effective as intravenous infusion in achieving positive clinical outcomes, but this has not been documented by randomized studies and its cost-effectiveness is unclear.

    Title Intravenous and Oral Lansoprazole Are Equivalent in Suppressing Stimulated Acid Output in Patient Volunteers with Erosive Oesophagitis.
    Date January 2005
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Some patients requiring acid suppression may be unable to take oral medications. AIM: To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients. METHODS: The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15. RESULTS: Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P < 0.001). CONCLUSIONS: Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications.

    Title Endoscopic Treatment Outcomes in Watermelon Stomach Patients with and Without Portal Hypertension.
    Date November 2004
    Journal Endoscopy
    Excerpt

    BACKGROUND AND STUDY AIMS: Watermelon stomach is a source of recurrent gastrointestinal hemorrhage and anemia. The aims of this study were to describe the endoscopic appearance and treatment outcomes in watermelon stomach patients with and without portal hypertension. PATIENTS AND METHODS: All patients with watermelon stomach enrolled in a hemostasis research group's prospective studies from 1991 to 1999 were identified. Investigators collected data using standardized forms. Comparisons were made using the chi-squared test, Wilcoxon rank-sum test, and Wilcoxon signed-rank test. RESULTS: Twenty-six of 744 (4 %) consecutively enrolled patients with nonvariceal upper gastrointestinal hemorrhage had watermelon stomach as the cause. Eight of these 26 patients (31 %) also had portal hypertension. These patients had diffuse antral angiomas, as opposed to the classic linear arrays seen in those without portal hypertension. The demographic data and clinical presentations of the two groups were otherwise similar. Palliative endoscopic treatment was associated with a significant rise in hematocrit and a decrease in the need for blood transfusion or hospitalization in watermelon stomach patients with and without portal hypertension. CONCLUSIONS: Watermelon stomach patients with and without portal hypertension had similar clinical presentations. The endoscopic findings differed in that those with portal hypertension had more diffuse gastric angiomas. Bleeding was effectively palliated by endoscopic treatment, regardless of the presence of portal hypertension.

    Title Lansoprazole in the Treatment of Functional Dyspepsia: Two Double-blind, Randomized, Placebo-controlled Trials.
    Date June 2004
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

    Title Endoscopic Treatment of Acute Esophageal Variceal Bleeding.
    Date October 2003
    Journal Drugs of Today (barcelona, Spain : 1998)
    Excerpt

    Improvements in pharmacologic and endoscopic therapy have greatly benefited patients with portal hypertension and acute UGI hemorrhage. The advent of endoscopic band ligation has provided a valuable therapeutic option. Sclerotherapy remains an important treatment alternative, especially in the setting of active bleeding and in cases of small varices that cannot be adequately treated with band ligation. Long-term prevention of variceal hemorrhage is possible only if obliteration is maintained. Regular endoscopic surveillance and retreatment are critical since varices may recur regardless of which endoscopic method is used for treatment.

    Title Major Stigmata of Recent Hemorrhage on Rectal Ulcers in Patients with Severe Hematochezia: Endoscopic Diagnosis, Treatment, and Outcomes.
    Date July 2003
    Journal Gastrointestinal Endoscopy
    Excerpt

    BACKGROUND: Endoscopic diagnosis and treatment of hematochezia caused by rectal ulcers is poorly described. METHODS: Consecutive patients hospitalized with severe hematochezia underwent urgent colonoscopy after purge. Those with rectal ulcers were divided into 2 groups based on the absence or presence of major stigmata of recent hemorrhage: active bleeding, visible vessel, or adherent clot. Major stigmata were treated with epinephrine injection and coagulation with a bipolar probe. The primary outcome endpoint was recurrent bleeding within 4 weeks of diagnosis. RESULTS: Rectal ulcers were identified in 23 of 285 (8%) patients. Twelve of 23 patients had major stigmata; these patients had an arithmetically greater decrease in hematocrit and required more blood transfusions than patients without major stigmata. Initial hemostasis was achieved in all, but bleeding recurred in 5 with stigmata. Four patients died of comorbid conditions. There was no recurrent bleeding or death in those without stigmata. CONCLUSIONS: Patients with rectal ulcers harboring major stigmata are at high risk for severe bleeding, recurrent bleeding, and death. For ulcers with major stigmata, endoscopic hemostasis is feasible but rates of recurrent bleeding are high.

    Title Rabeprazole is Superior to Omeprazole for the Inhibition of Peptone Meal-stimulated Gastric Acid Secretion in Helicobacter Pylori-negative Subjects.
    Date June 2003
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Peptone meal-stimulated gastric acid output is considered to be a reliable means to evaluate drug-mediated inhibition of stimulated gastric acid output, an important measure of the efficacy of the agents--such as proton pump inhibitors--used to treat acid-related disorders. AIM: To compare the initial and overall inhibitory effects on peptone meal-stimulated gastric acid secretion of rabeprazole and omeprazole, 20 mg, in Helicobacter pylori-negative subjects on the first and eighth days of treatment. METHODS: Healthy volunteers (n = 27) were randomized in a single-centre, double-blind, double-dummy, 2 x 2 cross-over study. Subjects received an oral dose of rabeprazole or omeprazole, 20 mg once daily, for 8 days. After a 2-4-week washout period, subjects were crossed over to receive the other medication for 8 days. Peptone meal-stimulated gastric acid secretion was measured at hours 11 and 23 at baseline and on days 1 and 8 of treatment. RESULTS: On days 1 and 8, rabeprazole demonstrated a significantly greater inhibition of peptone meal-stimulated gastric acid secretion compared with omeprazole at all time points (P < 0.03). Median values of steady-state inhibition on day 1 were statistically significant at hour 23 (rabeprazole 100% vs. omeprazole 74%, P < 0.02). CONCLUSIONS: Rabeprazole, 20 mg, demonstrated superior control of peptone meal-stimulated gastric acid secretion compared with omeprazole, 20 mg, after the first dose and after the eighth daily dose. Rabeprazole achieved a more rapid onset of acid inhibition and a greater steady-state reduction in peptone meal-stimulated gastric acid secretion.

    Title Comparison of the Efficacy of Pantoprazole Vs. Nizatidine in the Treatment of Erosive Oesophagitis: a Randomized, Active-controlled, Double-blind Study.
    Date March 2003
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Pantoprazole is a proton pump inhibitor approved for the treatment of erosive oesophagitis and gastro-oesophageal reflux disease. AIM: To compare the efficacy and safety of pantoprazole vs. nizatidine for the treatment of symptomatic gastro-oesophageal reflux disease and endoscopically documented erosive oesophagitis (grade > or = 2). METHODS: A multicentre, double-blind, randomized, active-controlled study (221 patients) was performed to compare 20 and 40 mg pantoprazole daily with nizatidine 150 mg b.d. (maximum, 8 weeks). The primary end-point was endoscopic healing of erosive oesophagitis (grade 1 or 0). The secondary end-point was symptomatic improvement. RESULTS: Healing averaged 61%, 64% and 22% for pantoprazole 20 mg, pantoprazole 40 mg and nizatidine 150 mg, respectively, at 4 weeks, and 79%, 83% and 41% at 8 weeks (P < 0.05, differences between groups at both points). Starting on day 1 of symptom assessment, significantly fewer pantoprazole-treated patients reported night-time heartburn and regurgitation compared with nizatidine-treated patients. Symptoms of gastro-oesophageal reflux disease were completely eliminated in 68% and 65% of patients in the pantoprazole 20-mg and 40-mg groups and in 28% of patients in the nizatidine group at study completion. The difference between each pantoprazole group and the nizatidine group was significant (P < 0.05). CONCLUSIONS: Pantoprazole, at single daily doses of 20 mg and 40 mg for up to 8 weeks, provides more rapid relief of symptoms and superior healing of erosive oesophagitis than nizatidine 150 mg b.d., and is well tolerated.

    Title Recent Advances in the Endoscopic Diagnosis and Therapy of Upper Gastrointestinal, Small Intestinal, and Colonic Bleeding.
    Date January 2003
    Journal The Medical Clinics of North America
    Excerpt

    Endoscopy has become the first and primary diagnostic and therapeutic modality in the management of patients with severe gastrointestinal bleeding. Panendoscopy, push enteroscopy, and colonoscopy provide the diagnostic, prognostic, and therapeutic elements to improve patient outcomes and to reduce morbidity and mortality from severe GI hemorrhage. Recent improvements in endoscopic hemostatic techniques and in imaging modalities using wireless capsule endoscopy suggest that diagnostic and therapeutic endoscopy will be even more important in determining patient outcomes in the future.

    Title Randomized Trial of Medical or Endoscopic Therapy to Prevent Recurrent Ulcer Hemorrhage in Patients with Adherent Clots.
    Date August 2002
    Journal Gastroenterology
    Excerpt

    BACKGROUND & AIMS: Treatment of high-risk patients with nonbleeding adherent clots on ulcers is controversial. In a previous randomized trial, there was no benefit to endoscopic therapies compared with medical therapy for prevention of ulcer rebleeding. Our purpose was to test the hypothesis that patients treated with combination endoscopic therapy would have significantly lower rebleeding rates than those treated with medical therapy. METHODS: In this randomized, controlled trial, 32 high-risk patients with severe ulcer hemorrhage and nonbleeding adherent clots resistant to target irrigation were randomized to medical therapy or to combination endoscopic therapy (with epinephrine injection, shaving down the clot with cold guillotining, and bipolar coagulation on the underlying stigmata). Physicians blinded to the endoscopic therapy managed all patients. RESULTS: Patients were similar at study entry, except for older age in the medical group and lower platelet count in the endoscopic group. By hospital discharge, significantly more medically treated patients (6/17; 35.3%) than endoscopically treated patients (0/15; 0%) rebled (P = 0.011). There were no complications of endoscopic treatment. CONCLUSIONS: Combination endoscopic therapy of nonbleeding adherent clots significantly reduced early ulcer rebleeding rates in high-risk patients compared with medical therapy alone. This endoscopic treatment was safe.

    Title Comparing Lansoprazole and Omeprazole in Onset of Heartburn Relief: Results of a Randomized, Controlled Trial in Erosive Esophagitis Patients.
    Date January 2002
    Journal The American Journal of Gastroenterology
    Excerpt

    OBJECTIVE: This randomized, double-blind, multicenter study was conducted to confirm a previous finding that lansoprazole relieves heartburn faster than omeprazole in patients with erosive esophagitis. METHODS: A total of 3510 patients with erosive esophagitis and at least one episode of moderate to very severe daytime and/or nighttime heartburn during the 3 days immediately before the screening visit were randomized to lansoprazole 30 mg once daily or omeprazole 20 mg once daily for 8 wk. Patients recorded the presence and severity of daytime and nighttime heartburn in daily diaries. On treatment days 1-4, patients were telephoned to confirm the completion of their daily diary. The primary efficacy parameters were the percentage of heartburn-free days and heartburn-free nights, as well as the average severity of daytime and nighttime heartburn. RESULTS: During treatment day I and all evaluation time points including the entire 8-wk treatment period, significantly (p < 0.05) higher percentages of patients treated with lansoprazole than those treated with omeprazole did not experience a single episode of heartburn. Onset of heartburn relief was more rapid in lansoprazole-treated versus omeprazole-treated patients: on day 1, 33% versus 25% of lansoprazole- versus omeprazole-treated patients were heartburn-free. The percentages of heartburn-free days and heartburn-free nights were also significantly (p < 0.01) greater for patients treated with lansoprazole at all evaluation time points. Heartburn severity was significantly less among those treated with lansoprazole compared with omeprazole. Both treatments were safe and well tolerated. CONCLUSIONS: Over 8 wk, lansoprazole 30 mg once daily relieved heartburn symptoms faster and more effectively than omeprazole 20 mg once daily in patients with erosive esophagitis.

    Title Omeprazole 40 Mg Once a Day is Equally Effective As Lansoprazole 30 Mg Twice a Day in Symptom Control of Patients with Gastro-oesophageal Reflux Disease (gerd) Who Are Resistant to Conventional-dose Lansoprazole Therapy-a Prospective, Randomized, Multi-centre Study.
    Date January 2001
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Comparative studies of omeprazole and lansoprazole are scarce and even scarcer are comparisons of higher doses. Most of the comparative studies have assessed the effect of the two proton pump inhibitors (PPIs) on gastric acid secretion or gastric pH. Few studies have compared clinical end-points such as oesophageal healing and symptom control. AIM: To determine the clinical efficacy of omeprazole 40 mg daily as compared to lansoprazole 30 mg twice a day in symptom control of patients with severe symptomatic GERD. METHODS: Ninety-six patients who failed a standard dose of lansoprazole (30 mg once daily), were enrolled in a prospective fashion from three VA medical centres and were randomized to receive 6 weeks of either omeprazole 40 mg daily or lansoprazole 30 mg twice daily. Patients reported daily on symptom severity and frequency, antacid consumption and side-effects. RESULTS: Forty-six patients received omeprazole and 44 lansoprazole. Although not statistically significant, there was a consistent trend of better symptom control in the omeprazole group for daytime and night-time heartburn and acid regurgitation. There was no statistical difference between the two groups in mean antacid consumption overall and at the end of each of the 6 weeks of the study. In addition, there was no significant difference in the overall frequency of side-effects between the two groups nor for each individual side-effect. CONCLUSION: Omeprazole 40 mg once daily is equally effective and tolerated as lansoprazole 30 mg twice daily in symptom control of patients with GERD.

    Title Rabeprazole Produces Rapid, Potent, and Long-acting Inhibition of Gastric Acid Secretion in Subjects with Helicobacter Pylori Infection.
    Date July 2000
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    AIM: To compare acid inhibiting activity and duration of action of different doses of rabeprazole, a substituted benzimidazole characterized as a highly potent and irreversible H+, K+-ATPase inhibitor, administered for 7 days to subjects infected with Helicobacter pylori. METHODS: A total of 38 subjects (mean age 39.3 years) were enrolled in a single-centre, double-blind, randomized, crossover study. All subjects were confirmed positive for H. pylori by 14C urea breath test and ELISA serologies. Subjects were divided into two groups of 19 to receive two doses of rabeprazole, either 5 and 20 mg or 10 and 40 mg, and placebo, given in random order daily in the morning for 7 days. Peptone-stimulated acid, pH, and gastrin measurements were made for 24 h after the 1st dose and for 48 h after the 7th dose. RESULTS: Peptone-stimulated acid secretion rates were decreased from 12.5 to 6.7, 4.0, 1.5, and 0.26 h after initial 5, 10, 20, and 40 mg doses, respectively; to 7.3, 4.3, 2.1, and 1.2 mmol/h 23 h after the initial dose; and to 2.4, 2.6, 0.6, and 0.8 mmol/h 23 h after the 7th dose. After 48 h, stimulated acid secretion had recovered less than 40% for all treatment groups compared to placebo. Median intragastric pH also increased from 2.0 with placebo to 4.9, 6.2, 6.6 and 6.9 during the 24-h period after the 7th dose of 5, 10, 20, and 40 mg. The 20 mg dose of rabeprazole produced equivalent acid inhibition to the 40 mg dose with less increase in plasma gastrin. CONCLUSION: Rabeprazole in doses from 5 to 40 mg was a highly effective inhibitor of gastric acid secretion in subjects infected with H. pylori. The inhibition was rapid, dose-related, and long-acting, with less than 50% recovery of acid by 48 h after the 7th dose. The optimal acid inhibitory dose in these subjects appeared to be 20 mg daily, however 5 mg and 10 mg doses produced potent inhibition of gastric acid secretion.

    Title Urgent Colonoscopy for the Diagnosis and Treatment of Severe Diverticular Hemorrhage.
    Date January 2000
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain. METHODS: We studied the role of urgent colonoscopy in the diagnosis and treatment of 121 patients with severe hematochezia and diverticulosis. All patients were hospitalized, received blood transfusions as needed, and received a purge to rid the colon of clots, stool, and blood. Colonoscopy was performed within 6 to 12 hours after hospitalization or the diagnosis of hematochezia. Among the first 73 patients, those with continued diverticular bleeding underwent hemicolectomy. For the subsequent 48 patients, those requiring treatment received therapy, such as epinephrine injections or bipolar coagulation, through the colonoscope. RESULTS: Of the first 73 patients, 17 (23 percent) had definite signs of diverticular hemorrhage (active bleeding in 6, nonbleeding visible vessels in 4, and adherent clots in 7). Nine of the 17 had additional bleeding after colonoscopy, and 6 of these required hemicolectomy. Of the subsequent 48 patients, 10 (21 percent) had definite signs of diverticular hemorrhage (active bleeding in 5, nonbleeding visible vessels in 2, and adherent clots in 3). An additional 14 patients in this group (29 percent) were presumed to have diverticular bleeding because although they had no stigmata of diverticular hemorrhage, no other source of bleeding was identified. The other 24 patients (50 percent) had other identified sources of bleeding. All 10 patients with definite diverticular hemorrhage were treated endoscopically; none had recurrent bleeding or required surgery. CONCLUSIONS: Among patients with severe hematochezia and diverticulosis, at least one fifth have definite diverticular hemorrhage. Colonoscopic treatment of such patients with epinephrine injections, bipolar coagulation, or both may prevent recurrent bleeding and decrease the need for surgery.

    Title Double-blind Comparison of Lansoprazole 15 Mg, Lansoprazole 30 Mg and Placebo As Maintenance Therapy in Patients with Healed Duodenal Ulcers Resistant to H2-receptor Antagonists.
    Date August 1999
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease. METHODS: Fifty-six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m. RESULTS: Within 1 month of study initiation, 27% (four out of 15) of placebo-treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty-two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups. CONCLUSIONS: Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer-related symptoms.

    Title Lansoprazole in the Treatment of Heartburn in Patients Without Erosive Oesophagitis.
    Date July 1999
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastro-oesophageal reflux disease (GERD). METHODS: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. RESULTS: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night-time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. CONCLUSIONS: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD.

    Title The Economic Impact of Esophageal Variceal Hemorrhage: Cost-effectiveness Implications of Endoscopic Therapy.
    Date February 1999
    Journal Hepatology (baltimore, Md.)
    Excerpt

    Esophageal variceal hemorrhage (EVH) is a serious and expensive sequela of chronic liver disease, leading to increased utilization of resources. Today, endoscopic sclerotherapy (ES) and endoscopic ligation (EL) are the accepted, community standards of endoscopic treatment of patients with EVH. However, there are no published studies comparing the economic costs of treating EVH using these interventions. As part of a prospective, randomized trial comparing ES and EL for the treatment of EVH, we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up. Treatment groups were similar in incidence of variceal rebleeding (41.9% vs. 42.9%), variceal obliteration (41.9% vs. 40.0%), hospital days, blood transfusions, shunt requirements, and survival (71.0% vs. 60.0%). There were significantly more treatment failures for active bleeding using EL (42% vs. 0%; P =.027) and esophageal stricture formation in the ES-treated patients (19.4% vs. 2.9%; P = 0.03). Median total direct cost outcomes were similar between groups (EL = $9,696 and ES = $13,197; P =.46). EL and ES had similar cost/variceal rebleeding prevented ($28,678 vs. $29,093) and cost/survival ($27,313 vs. $23,804). In the subgroup of active bleeders, ES had a substantially lower cost/survival ($28,523 vs. $51,696). We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds. Further studies comparing costs and resource utilization in this patient population are needed.

    Title Clinical and Economic Outcomes of Individuals with Severe Peptic Ulcer Hemorrhage and Nonbleeding Visible Vessel: an Analysis of Two Prospective Clinical Trials.
    Date December 1998
    Journal The American Journal of Gastroenterology
    Excerpt

    OBJECTIVE: We report the clinical outcomes and direct medical costs of 155 patients with severe peptic ulcer hemorrhage and a nonbleeding visible vessel at emergency endoscopy treated with endoscopic hemostasis or medical-surgical therapy. METHODS: In two consecutive, prospective, randomized, controlled trials, patients were randomly assigned to endoscopic hemostasis (heater probe, bipolar electrocoagulation, or injection sclerosis) or medical-surgical treatment. Study endpoints included the incidence of severe ulcer rebleeding and emergency surgery, length of hospital stay, blood transfusion requirements, mortality rate, and direct costs of utilized health care. Direct medical costs were estimated using combined fixed and variable institutional costs for consumed resources and Medicare reimbursement rates. RESULTS: Compared with medical-surgical treatment, endoscopically treated patients had significantly lower rates of severe ulcer rebleeding (p = 0.004), emergency surgery (p = 0.002 and p = 0.019, 0.024), and blood transfusions (p = 0.025). Observed inter-trial differences in ulcer rebleeding rates may be partially explained in a multivariate model by covariates of comorbid disease and inpatient ulcer bleeding. In both trials, length of hospital stay, mortality rates, and treatment-related complications were similar. Estimated median direct costs per patient differed: The first trial had lower costs with endoscopic hemostasis ($4254, vs $4620 for electrocoagulation and $5909 for medical-surgical treatment), yet the second trial yielded lower costs with medical-surgical treatment ($3169, vs $3477 for injection sclerosis and $4098 for heater probe). CONCLUSIONS: Compared with medical-surgical therapy, endoscopic hemostasis for severe ulcer hemorrhage and a nonbleeding visible vessel yielded significantly better patient outcomes and was safe. This procedure may or may not yield lower direct medical costs and cost savings.

    Title An Ascending Single-dose Safety and Tolerance Study of an Oral Formulation of Rabeprazole (e3810).
    Date October 1998
    Journal Alimentary Pharmacology & Therapeutics
    Excerpt

    BACKGROUND: Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin. Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non-competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia. AIM: This randomized, double-blind, placebo-controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin. METHODS: In this study, four groups of 10 healthy, non-smoking Helicobacter pylori-negative men (mean age 22.5 +/- 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double-blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24-h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24-h measurement of intragastric pH. During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels. RESULTS: Administration of rabeprazole resulted in a dose-dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose-related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t1/2 of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events. CONCLUSIONS: The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion.

    Title A Comparison of 10 and 14 Days of Lansoprazole Triple Therapy for Eradication of Helicobacter Pylori.
    Date September 1998
    Journal Archives of Internal Medicine
    Excerpt

    BACKGROUND: Data from large, multicenter, US studies determining the efficacy of triple therapy for the eradication of Helicobacter pylori are lacking, especially for a treatment duration of less than 14 days. METHODS: Patients with H pylori infection and active duodenal ulcer disease or a history of duodenal ulcer disease within the past year were randomized to receive 30 mg of lansoprazole, 1 g of amoxicillin, and 500 mg of clarithromycin twice daily for 10 or 14 days. The primary efficacy end point was the eradication of H pylori as confirmed by negative histological and culture results at 4 to 6 weeks after the completion of treatment. RESULTS: Of 284 patients enrolled in the study from 46 US sites, 236 met the entry criteria. At 4 to 6 weeks after the end of therapy, H pylori was eradicated in 85% (96/ 113) of the patients receiving 14-day triple therapy and in 84% (103/123) of those receiving 10-day triple therapy by per-protocol analysis (95% confidence interval for treatment group differences, -10.5 to 8.1; P>.05). There was also no significant difference between the 14- and 10-day treatment groups when analyzed by an intent-to-treat analysis of H pylori eradication. A similar proportion of patients in each treatment group reported an adverse event related to therapy (34% [46/136] vs 38% [56/148], respectively). CONCLUSIONS: In patients with an active or a recent history of duodenal ulcer, lansoprazole-based triple therapy for 10 or 14 days is highly effective in the eradication of H pylori. The duration of therapy may be reduced from 14 to 10 days without a significant effect on regimen efficacy.

    Title Double-blind Comparison of Lansoprazole 15 Mg, Lansoprazole 30 Mg, and Placebo in the Maintenance of Healed Gastric Ulcer.
    Date May 1998
    Journal Digestive Diseases and Sciences
    Excerpt

    Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30 mg with placebo in preventing recurrence in 49 patients with a history of gastric ulcer. Within one month, 40% of patients receiving placebo experienced ulcer recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30 mg, respectively. All placebo patients became symptomatic, experienced ulcer recurrence or withdrew from the study by month 9. As compared to placebo, a significantly (P < 0.001) higher percentage of patients treated with lansoprazole 15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59% of those treated with lansoprazole 15 mg and 30 mg, respectively, remained asymptomatic at month 12. The incidence of adverse events was comparable among the treatment groups. Lansoprazole safely and effectively reduces ulcer recurrence in patients with a history of gastric ulcer disease.

    Title An Economic Analysis of Patients with Active Arterial Peptic Ulcer Hemorrhage Treated with Endoscopic Heater Probe, Injection Sclerosis, or Surgery in a Prospective, Randomized Trial.
    Date October 1997
    Journal Gastrointestinal Endoscopy
    Excerpt

    BACKGROUND: There are no published, detailed assessments of the direct costs of endoscopic hemostasis for actively bleeding peptic ulcers. We compared the direct costs of care for patients with active ulcer hemorrhage treated with endoscopic or medical-surgical therapies and correlated these costs with patient outcomes. METHODS: In a prospective, randomized, controlled trial, 31 patients with active ulcer hemorrhage at emergency endoscopy were randomly assigned to heater probe, injection, or medical-surgical treatment. For further ulcer bleeding, heater probe and injection patients were re-treated endoscopically and medical-surgical patients were referred for surgery. Direct costs were estimated using fixed and variable costs for resources consumed and Medicare reimbursement rates for physician fees. RESULTS: Compared to medical-surgical treatment, the heater probe and injection groups had significantly higher primary hemostasis rates (100% and 90% vs 8%) and lower rates of emergency surgery (0% and 10% vs 75%), blood transfusions, and median direct costs per patient ($4153 and $5247 vs $11,149). Furthermore, compared to medical-surgical treatment, the heater probe group had a significantly lower incidence of severe ulcer rebleeding (11% vs 75%). CONCLUSIONS: Heater probe and injection sclerosis are similarly efficacious treatments for active ulcer hemorrhage, and both treatments yield significantly lower direct costs of medical care and cost savings.

    Title Inhibition of Sham Feeding-stimulated Acid Secretion in Dogs by Immunoneutralization of Gastrin.
    Date September 1997
    Journal The American Journal of Physiology
    Excerpt

    A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.

    Title Esophageal Motility Abnormalities in Cirrhotic Patients Before and After Endoscopic Variceal Treatment.
    Date July 1997
    Journal The American Journal of Gastroenterology
    Excerpt

    Esophageal motility abnormalities in patients treated endoscopically for variceal hemorrhage are rarely studied and usually are not addressed in the clinical setting. However, a review of the literature revealed that esophageal varices reduce the mean amplitude and increase the mean duration of peristaltic waves but have little effect on lower esophageal sphincter function. Transit time is delayed and gastroesophageal reflux disease is common in up to 64% of the patients. Whereas band ligation appears to have little impact on esophageal motility, data are limited and are hampered by lack of standardization, rendering conclusions about safety rather premature. Injection sclerotherapy spares the lower esophageal sphincter, as well, but it significantly reduces mean amplitude contractions, mainly in the lower one-third to one-half of the esophagus. In addition, normal peristalsis may be occasionally or completely replaced by nonpropagating simultaneous contractions that may result in chest pain and/or dysphagia in the absence of stricture. Transient prolongation of acid clearance usually resolves within a week, except in patients who have developed stricture. Pathogenesis of the abnormal motility remains poorly understood, and treatment has been empirical. However, a short course of anti-reflux treatment after each therapeutic session is justified, as well as long-term treatment for patients with stricture. The choice of treatment for esophageal motility abnormalities is less clear and requires future studies.

    Title Gastrin Partially Mediates Insulin-induced Acid Secretion in Dogs.
    Date January 1997
    Journal Peptides
    Excerpt

    A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating insulin-stimulated acid output. On separate days, seven adult dogs with chronic gastric fistulas were pretreated i.v. with either 1) 7 mg of a gastrin monoclonal antibody (mAb 28.2); 2) 12.5 micrograms/kg atropine; 3) mAb 28.2 and atropine together; or 4) vehicle (0.1% canine serum albumin in 0.15 M NaCl). Thirty minutes later, acid secretion was stimulated by insulin (0.5 U/kg, i.v.), followed in 2 h by a 1-h infusion of histamine (40 micrograms/kg/h, i.v.). Acid output (mmol/15 min) in gastric effluent collected through the gastric fistula was determined by titration with 0.2 N NaOH to pH 7.0. Plasma gastrin was measured by radioimmunoassay. Plasma glucose was measured by a glucose oxidase method on an auto analyzer. Insulin induced a profound hypoglycemia (55 +/- 8 mg/dl) that coincided with a marked increase in acid output to 7.1 +/- 0.6 mmol/30 min by 45 min after injection. MAb 28.2 pretreatment and atropine pretreatment reduced insulin-stimulated acid outputs to 2.7 +/- 0.7 mmol/30 min and to 0.6 +/- 0.2 mmol/ 30 min, respectively. Acid output after combined pretreatment (0.5 +/- 0.2 mmol/30 min) was not significantly different than after atropine alone. Histamine-stimulated acid output (15.8 +/- 2.5 mmol/30 min) was not significantly reduced by any pretreatment. Insulin injection increased circulating gastrin concentrations to 32 +/- 7 fmol/ml, which was not significantly affected by atropine (39 +/- 9 fmol/ml). This study demonstrates that, in dogs, a significant part of insulin-stimulated acid secretion is mediated by circulating gastrin.

    Title Severe Upper Gastrointestinal Tumor Bleeding: Endoscopic Findings, Treatment, and Outcome.
    Date September 1996
    Journal Endoscopy
    Excerpt

    BACKGROUND AND STUDY AIMS: The aim of the present study was to review endoscopic findings, treatment, and clinical outcomes in patients with severe upper gastrointestinal bleeding due to tumors. PATIENTS AND METHODS: A retrospective analysis was made of prospectively gathered data on all patients with severe upper gastrointestinal bleeding who were admitted to two large referral centers during a 45-month period. RESULTS: Nine hundred thirty-five patients had severe upper gastrointestinal bleeding, of whom 42 (5%) were found to have tumors. Histologically, nearly all of the tumors were of a malignant type. Fifty-two percent of the patients had acute severe upper gastrointestinal bleeding as the initial presentation of their tumor. The most common tumor was gastric adenocarcinoma, and all of these cases were at advanced stages. Endoscopic hemostasis with thermal probes or epinephrine injection, or both, was carried out in seven patients (17%), with successful hemostasis in all of the tumors. Regardless of the treatment given, patients with upper gastrointestinal tumor bleeding, had a 30-day surgery rate of 43%, a 30-day rebleed rate of 33%, a 30-day mortality rate of 10%, and a 1-year mortality rate of 89%. CONCLUSIONS: Most tumors that cause severe upper gastrointestinal bleeding are of a malignant histologic type and are already at an advanced stage. Endoscopic hemostasis of bleeding upper gastrointestinal tumors is safe and initially effective, and may provide time for elective surgical palliation. Regardless of therapy, upper gastrointestinal tumors with severe bleeding have a poor one-year survival.

    Title Inhibition of Bombesin-stimulated Acid Secretion by Immunoneutralization of Gastrin in Dogs.
    Date February 1995
    Journal The American Journal of Physiology
    Excerpt

    Bombesin-like peptides stimulate gastrin release and gastric acid secretion. The increase in gastric acid output is thought to be secondary to gastrin release. A monoclonal antibody (MAb) directed specifically to gastrin (MAb 28.2) was used to study the role of circulating gastrin in the regulation of bombesin-stimulated acid secretion in dogs. Seven conscious, fasted dogs with gastric fistulas received intravenous bombesin infusions in fourfold increasing doses from 200 to 3,200 pmol.kg-1.h-1. Each dose was given for 45 min. On separate days, dogs were pretreated with an intravenous infusion of 7 mg of MAb 28.2 or vehicle (0.1% canine serum albumin). Samples of gastric effluent were collected by gravity drainage through the gastric fistula, and acid output was measured by titration of gastric effluent to pH 7.0, using 0.2 N NaOH. Plasma gastrin concentrations were determined by radioimmunoassay. Bombesin infusion produced dose-dependent increases in plasma gastrin concentrations and gastric acid output. Administration of gastrin MAb 28.2 abolished bombesin-stimulated gastric acid output. Immunoneutralization of circulating gastrin in vivo using a gastrin monoclonal antibody in dogs indicates that the acid stimulatory response to bombesin is mediated by gastrin.

    Title Octreotide Decreases Canine Gastric Mucosal Blood Flow: a Controlled Assessment by Endoscopic Reflectance Spectrophotometry.
    Date May 1994
    Journal Gastrointestinal Endoscopy
    Excerpt

    The aim of this study was to evaluate the effects of octreotide, a long-acting somatostatin analogue, on canine gastric mucosal blood flow and hemodynamics. We hypothesized that octreotide might decrease gastric mucosal blood flow without causing adverse hemodynamic effects. Two groups of dogs were anesthetized (six normal dogs and six dogs with prehepatic portal hypertension), and each dog was administered intravenous octreotide, normal saline solution, and vasopressin for 30 minutes on separate days in a blinded, randomized fashion. Vasopressin was included as treatment for a positive control. Gastric mucosal blood flow was assessed at the fundus, corpus, and antrum by endoscopic reflectance spectrophotometry. A femoral arterial catheter monitored systemic blood pressure and heart rate. Treatment responses for all observations were calculated for each dog as a percentage of baseline values. For mucosal blood flow, treatment responses did not differ significantly over time or between animal group or gastric location. Octreotide significantly decreased indices of hemoglobin concentration (-19%, p = 0.01) and oxygen saturation (-17%, p = 0.0002) compared to saline (-9% and -7%, respectively). The mean arterial pressure was increased after octreotide compared to saline (+23% versus +7%, p = 0.01), but octrotide had no effect on heart rate (+2% versus +1%). Vasopressin also decreased the indices of hemoglobin concentration (-34%) and oxygen saturation (-82%) significantly more than saline (p = 0.001). Vasopressin increased mean arterial pressure (+55%), but also caused reflex bradycardia (-22%) significantly more than saline (p = 0.001). We conclude that octreotide decreases canine gastric mucosal blood flow and appears to cause minimal hemodynamic changes.

    Title A Controlled Study of Ranitidine for the Prevention of Recurrent Hemorrhage from Duodenal Ulcer.
    Date February 1994
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND. Hemorrhage is the most common complication of duodenal ulcer disease, but there is little information about the effectiveness and safety of long-term maintenance therapy with histamine H2-receptor blockers. METHODS. We conducted a double-blind study in patients with endoscopically documented hemorrhage from duodenal ulcers. Patients were randomly assigned to maintenance therapy with ranitidine (150 mg at night) or placebo and were followed for up to three years. Endoscopy was performed at base line (to document that the ulcers had healed), at exit from the study, and when a patient had persistent ulcer symptoms unrelieved by antacids or had gastrointestinal bleeding. Symptomatic relapses without bleeding were treated with ranitidine; if the ulcer healed within eight weeks, the patient resumed taking the assigned study medication. RESULTS. The two groups were similar at entry, which usually occurred about three months after the index hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo (P < 0.05). Half the episodes of recurrent bleeding were asymptomatic. One patient in the ranitidine group withdrew from the study because of asymptomatic thrombocytopenia during the first month. CONCLUSIONS. For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding.

    Title The Gastrin-receptor Antagonist L-365,260 Inhibits Stimulated Acid Secretion in Humans.
    Date December 1993
    Journal Clinical Pharmacology and Therapeutics
    Excerpt

    We investigated the effect of a novel gastrin-cholecystokinin-B receptor antagonist, L-365,260 [(3R)-3(N'-3-methylphenyl)ureido)-1,3-dihydro-5-phenyl- 2H-1,4-benzodiazepin-2-one], on gastric acid secretion in humans. In a double-blind, four-period crossover study, eight subjects received single oral doses of placebo or of 2.5, 10, or 50 mg L-365,260, followed by an intravenous infusion of pentagastrin at doses of 0.05, 0.4, and 2 micrograms/kg/hr for successive 30-minute periods. L-365,260 caused a dose-dependent inhibition of pentagastrin-stimulated gastric acid secretion. A single oral dose of 50 mg L-365,260 produced 50% inhibition of the gastric acid output response to pentagastrin (0.4 micrograms/kg/hr) when the mean (+/- SD) plasma L-365,260 concentration was 502 +/- 108 ng/ml. Plasma L-365,260 concentrations (all doses combined) and the inhibition of gastric acid output were correlated with a correlation coefficient of r = 0.45 (p < 0.05). Single oral doses of L-365,260 up to 50 mg did not inhibit basal gastric acid output or alter plasma gastrin concentrations. L-365,260 was well tolerated at oral doses up to 50 mg. These findings show that L-365,260 is an orally active antagonist at gastrin-cholecystokinin-B receptors in humans.

    Title Asymptomatic H. Pylori Infection Impairs Ph Inhibition of Gastrin and Acid Secretion During Second Hour of Peptone Meal Stimulation.
    Date September 1993
    Journal Digestive Diseases and Sciences
    Excerpt

    H. pylori infection is associated with acid-peptic disease, although its role in the pathogenesis is unclear. The purpose of this study was to determine if chronic infection in asymptomatic subjects impairs the inhibition of meal-stimulated gastrin and acid secretion that is observed normally at low intragastric pH. Presence of infection was determined by both C-14 urea breath test and serology. Acid secretion was measured under basal conditions and in response to peptone meal stimulation and pentagastrin. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and during peptone meal stimulation. Intragastric titration with 1% peptone during the first hour, and 8% peptone during the second hour, was performed at both pH 7.0 and 2.5 on different days to compare the inhibition of gastrin and acid secretion. Compared to noninfected subjects, asymptomatic individuals infected with H. pylori had significantly increased: (1) basal gastrin values (P < 0.005); (2) 8% peptone-stimulated gastrin responses at both pH 7.0 and 2.5 (P < 0.05); and (3) 8% peptone-stimulated acid output at pH 2.5 (P = 0.01). During the second hour of peptone-stimulation, subjects infected with H. pylori had significantly decreased inhibition of gastrin (52% vs 95%) (P = 0.002) and acid (30% vs 81%) (P = 0.01) secretion from pH 7.0 to 2.5. Thus, chronic infection with H. pylori results in impaired inhibition of gastrin and acid secretion at low intragastric pH during the second hour of peptone meal stimulation. These defects may be unrelated to the pathogenesis of acid-peptic disease, since they occur in asymptomatic subjects infected with H. pylori.

    Title Regulation of Gastric Acid Secretion by Gastrin in Duodenal Ulcer Patients and Healthy Subjects.
    Date April 1992
    Journal Gastroenterology
    Excerpt

    To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

    Title Cholecystokinin Receptor Antagonist Mk-329 Blocks Intestinal Fat-induced Inhibition of Meal-stimulated Gastric Acid Secretion.
    Date January 1992
    Journal Gastroenterology
    Excerpt

    MK-329, a selective type A cholecystokinin (CCK) receptor antagonist, was given to dogs to test the hypothesis that CCK is one of the principal physiological enterogastrones mediating fat-induced decreases in gastric acid secretion. Gastric acid secretion in response to 300 mL 8% peptone meals was measured by intragastric titration to pH 5.5 in six awake dogs with chronic gastric, duodenal, and jejunal fistulas. Gastric emptying was measured by a dye-dilution technique. During the last hour of peptone stimulation, the intestine was perfused with either control solution or 20% lipid (Intralipid; Kabi Vitrum, Alamedo, CA) intraduodenally or intrajejunally. Compared with control perfusions, mean gastric acid outputs were decreased significantly after lipid perfusion of the duodenum (47% of control) and jejunum (24% of control). Similarly, mean gastric emptying rates were significantly less after lipid perfusion of the duodenum (56%) and jejunum (26%). Oral pretreatment with MK-329 (1 mg/kg) significantly reversed the inhibition of gastric acid output caused by lipid perfusion of the duodenum and jejunum, but fat-induced inhibition of gastric emptying was not significantly affected. These studies provide evidence for an important inhibitory role for CCK as an enterogastrone but do not implicate CCK as being important in fat-induced delayed gastric emptying of a liquid meal in dogs.

    Title Preclinical Evaluation of an Anti-autocrine Growth Factor Monoclonal Antibody for Treatment of Patients with Small-cell Lung Cancer.
    Date November 1991
    Journal Journal of the National Cancer Institute
    Excerpt

    We have evaluated an anti-autocrine growth factor monoclonal antibody for potential use in the treatment of patients with small-cell lung cancer. The monoclonal antibody, designated 2A11, binds to the C-terminal region of the autocrine growth factor gastrin-releasing peptide and neutralizes its growth-promoting effects in vitro and in vivo. Equilibrium-binding analysis demonstrated that the peptide binds to the antibody (dissociation constant = 1.5 x 10(-10) at least as avidly as it binds to the tumor peptide receptor. Pharmacokinetic studies in normal BALB/c mice demonstrated an initial clearance half-life (alpha t1/2) of 24.3 +/- 4 hours and a secondary clearance half-life (beta t1/2) of 1039.6 +/- 309 hours, and biodistribution studies revealed a distribution pattern which generally reflected blood flow. Single intravenous infusions of 2A11 (20 mg/20-25-kg dogs) into normal mongrel dogs with surgically created gastric fistulas antagonized the stimulatory effects of exogenously infused gastrin-releasing peptide or bombesin on plasma gastrin release and gastric acid secretion. Toxicology studies in normal dogs (with gastric fistulas) infused with 50 mg 2A11 intravenously three times a week for 4 weeks failed to reveal any adverse behavioral, clinical, or pathological effects. Four of six dogs developed an immune response to 2A11. Anti-idiotypic antibodies elicited in two cases did not mimic the functional effects of the peptide. We conclude that the concept of immunoblockade of an autocrine growth factor appears feasible in vivo.

    Title Gastrin is a Major Mediator of the Gastric Phase of Acid Secretion in Dogs: Proof by Monoclonal Antibody Neutralization.
    Date January 1990
    Journal Gastroenterology
    Excerpt

    We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg.h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg.h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients.

    Title Bombesin-like Peptides As Regulators of Gastric Function.
    Date May 1989
    Journal Annals of the New York Academy of Sciences
    Title The Effect of an Oral Evening Dose of Nizatidine on Nocturnal and Peptone-stimulated Gastric Acid and Gastrin Secretion.
    Date February 1988
    Journal Scandinavian Journal of Gastroenterology. Supplement
    Excerpt

    An evening oral dose of nizatidine, a new H2-receptor antagonist, was tested for its ability to suppress nocturnal gastric acid secretion and to inhibit food stimulated acid secretion the following day. Using a double-blind, randomized, cross-over design, nizatidine 30, 100, and 300 mg and placebo were compared in 8 male subjects with basal acid secretion greater than or equal to 3 mmol/h. Continuous nasogastric suction was started 2 h after oral dosing, and acid secretion was measured hourly overnight. Phenol red was used to determine the completeness of gastric aspiration. The following day, food stimulated acid secretion in response to 8% peptone meals was measured by intragastric titration to determine the carry-over effect of nizatidine. Serum gastrin levels were measured by RIA. Nizatidine inhibited overnight acid secretion in a dose-related manner with 30, 100, and 300 mg producing 57, 73, and 90% suppression. The effect was long-lasting, with nizatidine 300 mg decreasing acid secretion by 52% 10 h after administration. Peptone stimulated acid secretion on the following day was not inhibited by nizatidine. Gastrin levels did not differ significantly among the treatment groups. Nizatidine's effects on nocturnal acid secretion therefore resemble other H2-receptor antagonists.

    Title Endoscopic Control of Gastroduodenal Hemorrhage.
    Date June 1987
    Journal Annual Review of Medicine
    Excerpt

    Several methods of endoscopically controlling acute, nonvariceal upper gastrointestinal bleeding have been developed. Some, such as the laser, heater probe, and bipolar electrocoagulation, have been evaluated in controlled clinical trials. The purpose of this paper is to discuss endoscopic control of nonvariceal gastroduodenal hemorrhage and to consider whether improvement in outcome is likely with any of these devices. Techniques and results of controlled clinical trials are reviewed.

    Title Canine Bombesin-like Gastrin Releasing Peptides Stimulate Gastrin Release and Acid Secretion in the Dog.
    Date October 1985
    Journal The Journal of Physiology
    Excerpt

    The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.

    Title Abnormal Alanine Aminotransferase Level in Blood Units from Donors in Montreal Does Not Indicate High Risk of Transmitting Hepatitis.
    Date May 1984
    Journal Clinical and Investigative Medicine. Médecine Clinique Et Experimentale
    Excerpt

    We undertook a prospective study to estimate the risk in Montreal of developing hepatitis following transfusion of blood with an elevated alanine aminotransferase (ALT) level. Two thousand consecutive donor units were screened for ALT activity; 133 (6.7%) had values greater than or equal to 51 IU 1(-1). Twenty-four patients received one or more units with elevated ALT levels and completed follow-up; two (8%) developed hepatitis (one of these was type B hepatitis). One of the 10 'control' patients who received only units with normal ALT levels also developed hepatitis. In this study, the risk of transfusion-transmitted hepatitis was the same in recipients of blood units with abnormal ALT levels as in those who received only blood with normal ALT, and very similar to the risk reported in other studies for recipients of volunteer donor blood with normal ALT. These findings require confirmation by a larger study, but suggest that the hepatitis risk associated with transfusion of high-ALT blood may be lower in Montreal than has been reported in several centers in the U.S.

    Title Small Bowel Bleeding.
    Date
    Journal Current Treatment Options in Gastroenterology
    Excerpt

    The management of patients with small bowel bleeding remains a diagnostic and therapeutic challenge. In most gastrointestinal bleeding episodes, the source of hemorrhage is localized to either the upper gastrointestinal tract or colon; however, in about 5% of cases, upper endoscopy and colonoscopy are nondiagnostic, and the small intestine is the site of bleeding. Patients with suspected small bowel source of bleeding may present with either occult blood loss or recurrent overt gastrointestinal hemorrhage requiring frequent blood transfusions and hospitalizations. Knowing the etiology and site of hemorrhage is essential prior to initiating appropriate therapy. The most common causes of small bowel bleeding are vascular ectasia, tumors, ulcerative diseases, and Meckel's diverticula. For patients with severe obscure bleeding, push enteroscopy with a 220- to 250-cm enteroscope is strongly recommended. This procedure provides not only a thorough examination for diagnosis, but also allows for biopsy, tattooing, and hemostasis of lesions. If enteroscopy is nondiagnostic, capsule endoscopy is recommended. A diagnostic capsule endoscopy will direct appropriate medical, endoscopic, or surgical intervention, depending on whether the lesion is single or multiple, and whether the patient is a surgical candidate for intraoperative enteroscopy. Intraoperative enteroscopy should be strongly considered in patients with recurrent bleeding and a nondiagnostic evaluation. Laparoscopy and intraoperative enteroscopy is highly recommended in young patients (< 50 years of age) because there is an increased frequency of small bowel tumors and Meckel's diverticulum which are amenable to surgical therapy.

    Title Endoscopic Treatment of Ulcer Bleeding.
    Date
    Journal Current Treatment Options in Gastroenterology
    Excerpt

    Upper gastrointestinal (UGI) bleeding secondary to ulcer disease occurs commonly and results in significant patient morbidity and medical expense. After initial resuscitation, carefully performed endoscopy provides an accurate diagnosis of the source of the UGI hemorrhage and can reliably identify those high-risk subgroups that may benefit most from endoscopic hemostasis. Large-channel therapeutic endoscopes are recommended. Endoscopists should be very experienced in management of patients with UGI hemorrhage, including the use of various hemostatic devices. For patients with major stigmata of ulcer hemorrhage--active arterial bleeding, nonbleeding visible vessel, and adherent clot--combination therapy with epinephrine injection and either thermal coaptive coagulation (with multipolar or heater probe) or endoclips is recommended. High-dose intravenous proton-pump inhibitors are recommended as concomitant therapy with endoscopic hemostasis of major stigmata. Patients with minor stigmata or clean-based ulcers will not benefit from endoscopic therapy and should be triaged to less intensive care and be considered for early discharge. Effective endoscopic hemostasis of ulcer bleeding can significantly improve outcomes by reducing rebleeding, transfusion requirement, and need for surgery, as well as reduce cost of medical care.

    Title Lansoprazole for Long-term Maintenance Therapy of Erosive Esophagitis: Double-blind Comparison with Ranitidine.
    Date
    Journal Digestive Diseases and Sciences
    Excerpt

    In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P < 0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P < 0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P < 0.001). Symptom status correlated with healing (P = 0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief.

    Title The Short-term Medical Management of Non-variceal Upper Gastrointestinal Bleeding.
    Date
    Journal Drugs
    Excerpt

    Upper gastrointestinal (UGI) bleeding occurs frequently and results in substantial patient morbidity, mortality and medical expense. After initial resuscitation to stabilize the patient, carefully performed endoscopy provides an accurate diagnosis and can identify high-risk subgroups in ulcer patients who are likely to rebleed with medical therapy alone and would benefit most from endoscopic haemostasis. Several different pharmacological therapies have been used for patients with bleeding ulcers, including intravenous histamine H(2)-receptor antagonists, proton pump inhibitors, somatostatin and octreotide, and tranexamic acid. The results of several studies and meta-analyses favour high-dose, intravenous proton pump inhibitors, such as omeprazole or pantoprazole, after successful endoscopic haemostasis.For patients with ulcer bleeding and low-risk endoscopic stigmata, high-dose oral proton pump inhibitor therapy is suggested. Medical management with proton pump inhibitors is not a substitute for appropriate endoscopic therapy for patients with UGI bleeding and high-risk ulcer stigmata.

    Title Management of Upper Gastrointestinal Bleeding.
    Date
    Journal Current Gastroenterology Reports
    Excerpt

    Upper gastrointestinal bleeding secondary to ulcer disease is common and results in substantial patient morbidity and medical expense. After initial resuscitation to stabilize the patient, carefully performed endoscopy provides an accurate diagnosis and identifies high-risk ulcer patients who are likely to rebleed with medical therapy alone and will benefit most from endoscopic hemostasis. For patients with major stigmata of ulcer hemorrhage--active arterial bleeding, nonbleeding visible vessel, and adherent clot--combination therapy with epinephrine injection and either thermal coagulation (multipolar or heater probe) or endoclips is recommended. High-dose intravenous proton pump inhibitors are recommended as concomitant therapy after successful endoscopic hemostasis. Patients with minor stigmata or clean-based ulcers will not benefit from endoscopic treatment and should receive high-dose oral proton pump inhibitor therapy. Effective medical and endoscopic management of ulcer hemorrhage can significantly improve outcomes and decrease the cost of medical care by reducing rebleeding, transfusion requirements, and the need for surgery.

    Similar doctors nearby

    Dr. Stephen Derose

    Internal Medicine
    19 years experience
    Pasadena, CA

    Dr. Irram Rao

    Internal Medicine
    11 years experience
    Torrance, CA

    Dr. Rajesh Sodhi

    Internal Medicine
    Woodland Hills, CA

    Dr. David De La Loza

    Internal Medicine
    21 years experience
    Los Angeles, CA

    Dr. Warren Chow

    Internal Medicine
    24 years experience
    Duarte, CA

    Dr. Yoon Shin

    Internal Medicine
    8 years experience
    Los Angeles, CA
    Search All Similar Doctors