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Biomedical subjects

A R Opekun

Publications and source records attributed to A R Opekun.

At least 19 recordsLinked to original sources
PubMed1999

Novel therapies for Helicobacter pylori infection.

BACKGROUND: Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection. AIM: To evaluate orally administered novel therapies for the treatment of H. pylori infection. METHODS: Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1-4Glc-(3'-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. RESULTS: None of the novel therapies appeared effective and no adverse events occurred. CONCLUSION: Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

Adjuvants, Immunologic↗
PubMed1997

Lack of dose-response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults.

BACKGROUND: Choosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose-response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective. METHODS: In a randomized, single-blind, cross-over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20,000 units lipase), Pancrease MT16 (32,000 units lipase) or placebo. A 72-h quantitative faecal collection was carried out for the last 3 days of the 6-day period. RESULTS: There was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P > 0.05) but was significant (P = 0.02) with the 20,000 units lipase and the 32,000 units lipase preparations (faecal fat excretion: placebo = 42.1 +/- 29 g, lipase 8000 = 22.1 +/- 7.3 g, lipase 20,000 = 10.2 +/- 4.5 g and lipase 32,000 = 15.8 +/- 12.5 g, P < for 20,000 units and 32,000 units lipase compared to placebo). CONCLUSION: A dose-response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.

Adult↗
PubMed1996

Recombinant Norwalk virus-like particles as an oral vaccine.

Viruses that infect cells in the gastrointestinal tract are well suited for examining the immune response to oral delivery of antigen and for exploring the advantages and pitfalls of oral vaccines. Norwalk virus (NV) (family Caliciviridae, genus Calicivirus) causes acute gastroenteritis in all age groups. The NV capsid is composed of 180 copies of a single 58000 molecular weight protein which spontaneously forms virus-like particles (VLPs) that can be purified in extremely high yields (22 mg per 300 ml culture) when produced using the baculovirus expression system. We are testing the potential of these recombinant NV (rNV) particles for use as an oral vaccine by administering them to mice and volunteers. Mice were orally inoculated four times with rNV particles in concentrations ranging from 5 to 500 micrograms in the absence of adjuvant or from 5 to 200 micrograms with 10 micrograms of cholera toxin. Serum IgG and fecal IgA immune responses were monitored. rNV particles were found to be immunogenic when orally given to mice with or without adjuvant. These particles also were safe and immunogenic when orally given to volunteers. These studies show that rNV particles are an excellent model to test the oral delivery of mucosal immunogens in general, and that rNV particles are ideal candidates for vaccine development in particular.

Administration, Oral↗
PubMed1996

Helicobacter pylori in the drinking water in Peru.

BACKGROUND & AIMS: An association between water sources and the prevalence of Helicobacter pylori infection in Peruvian children was shown previously. The aim of this study was to confirm the presence of H. pylori in drinking water in the same community. METHODS: Forty-eight drinking water samples from different locations in pueblo jovenes (new towns) near Lima were collected. Samples were frozen until technology advanced to the point to the point at which H. pylori might be reliably detected. Immunomagnetic beads coated with anti-H. pylori immunoglobulin Gs were used to concentrate H. pylori, and two polymerase chain reaction assays based on different H. pylori genes were used. One was a polymerase chain reaction for the detection of the H. pylori adhesin subunit encoding gene, and the second was a previously validated H. pylori 16S ribosomal RNA reverse transcriptase-polymerase chain reaction. RESULTS: The expected 375-base pair fragment from the adhesin gene was amplified from 24 water samples. The expected 500-base pair fragment of the 16S ribosomal RNA and the 375-base pair fragment of the adhesin gene were amplified from 11 of the samples. CONCLUSIONS: These results confirm the presence of H. pylori in drinking water in Peru and are consistent with conclusions from a previous epidemiological study of the same population. This provides additional evidence for waterborne transmission of H. pylori in some environments.

Adhesins, Bacterial↗
PubMed1995

[13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives.

The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.

Adult↗
PubMed1995

Comparison of the effect of intermittent administration and continuous infusion of famotidine on gastric pH in critically ill patients: results of a prospective, randomized, crossover study.

OBJECTIVES: To compare the effects of intermittent intravenous administration and continuous intravenous infusion of famotidine on gastric pH in critically ill patients. DESIGN: A prospective, randomized, crossover study of continuous infusion and bolus administration of famotidine in critically ill patients. SETTING: A 14-bed medical intensive care unit (ICU) of a 500-bed county hospital. PATIENTS: Medical ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS: Patients were randomized to receive an equivalent dose of famotidine by continuous infusion or intravenous bolus for 24 hrs, and then were crossed over to the other arm of the study. MEASUREMENTS AND MAIN RESULTS: Critically ill patients who met the inclusion criteria were randomly assigned to receive famotidine 20 mg i.v. over 10 mins, every 12 hrs or a continuous infusion of 1.7 mg/hr for 24 hrs. After a 16-hr washout period, patients crossed over to the other arm of the study. Gastric pH was monitored continuously for 24 hrs. A total of 710 gastric pH measurements were obtained for each phase of the study. The mean area under the pH-time curve for a 24-hr period was higher for continuous infusion than bolus administration (p = .05). Continuous infusion of famotidine maintained a gastric pH of > or = 4 over a longer time period than bolus administration (20.8 hrs vs. 12.6 hrs, respectively; p < .01). Onset of therapeutic gastric pH for continuous infusion was slightly delayed as compared with bolus administration. CONCLUSIONS: Continuous infusion of famotidine is more effective than an equivalent dose given by intermittent bolus in maintaining the appropriate gastric pH necessary for prevention of stress ulceration. Delayed onset of effect may warrant a priming dose when famotidine is given by continuous infusion.

Adult↗
PubMed1994

Norwalk virus infection of volunteers: new insights based on improved assays.

Norwalk virus infection is a common cause of gastroenteritis in humans. The clinical features and virologic and immunologic responses following oral administration of Norwalk virus to 50 volunteers were monitored. New ELISAs using recombinant virus particles as the antigen source were used to assess the pattern of virus shedding and the specific immune responses. Forty-one subjects (82%) became infected; 68% were symptomatic and 32% were asymptomatic. The proportion of subjects infected was similar for those with and without preexisting antibody (82% vs. 60%; P > .2). The magnitude of seroconversion was highest in subjects who had vomiting. The peak of viral shedding was between 25 and 72 h, and virus first appeared in stool at 15 h. Specimens collected 7 days after inoculation remained positive. These results show a higher infection rate, more subclinical infections, and longer virus excretion following Norwalk virus inoculation than previously recognized.

Adult↗
PubMed1994

Leucine oxidation changes rapidly after dietary protein intake is altered in adult women but lysine flux is unchanged as is lysine incorporation into VLDL-apolipoprotein B-100.

We measured the 13C enrichments of expired CO2 and deuterium enrichments of plasma free lysine and VLDL-apolipoprotein B-100 in five nulliparous women who received an oral bolus dose of [1-13C]leucine and a primed, constant infusion of [2H4]lysine on d 2 and 6 while consuming protein diets of 1.5, 1.0 and 0.4 g.kg-1 x d-1. Peak enrichments and cumulative percent recoveries of 13C in expired CO2 increased during the high, and decreased during the low protein periods within 24 h of altered intakes; these changes averaged 89% of that on d 6 of the high and low protein diets. The early changes in leucine oxidation showed significant relationships with urinary nitrogen excretion on d 6 of the dietary periods. The ratio of the isotopic enrichment of lysine in VLDL-apolipoprotein B-100 to that in plasma was unaltered by the level of protein intake. Thus, amino acid oxidation adapts rapidly to altered protein intakes in adult women and is useful to determine protein needs during rapidly changing physiologic conditions. However, 6-d periods of protein intake over the range of 1.5 to 0.4 g.kg-1 x d-1 do not affect the proportional use of dietary amino acids for hepatic secretory protein synthesis.

Administration, Oral↗
PubMed1994

Equivalence of litmus paper and intragastric pH probes for intragastric pH monitoring in the intensive care unit.

OBJECTIVE: To compare the accuracy of litmus paper-determined gastric pH to a nasogastric graphite antimony pH probe. DESIGN: A prospective clinical trial of gastric pH determination in patients enrolled in a study of histamine-2-receptor (H2) antagonists. SETTING: The medical intensive care unit (ICU) of a 450-bed county hospital. PATIENTS: Critically ill ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS: Using a crossover design, the patients were randomized to initially receive an H2 antagonist by continuous infusion or intravenous bolus, and subsequently were crossed over to the other limb of the study. MEASUREMENTS AND MAIN RESULTS: Gastric pH was determined using pH-sensitive litmus paper at the initiation of each limb of the study and at 1, 2, 4, and 8 hrs after the initiation of H2 receptor antagonist therapy. In addition, gastric pH was continuously determined over the same time period utilizing a graphite antimony pH probe. Gastric pH measurements determined with litmus paper and intragastric pH probes demonstrated an excellent correlation (r2 = .93, p < .001). McNemar's test of correlated proportions could not demonstrate a significant difference between the two monitoring methods (chi-square = 0.5, p > .47), and the kappa statistic (0.95, p < .001) demonstrated excellent concordance. Bias measurement was 0.01 (95% confidence interval = -0.155 to 0.176). CONCLUSIONS: Measurement of intragastric pH, using pH-sensitive litmus paper, is both sensitive and specific when utilizing a graphite antimony nasogastric pH probe as a reference standard. Litmus paper-determined gastric pH testing is both easy to perform and inexpensive. Therefore, based on the current data, we believe this technique (i.e., litmus paper determined gastric pH testing) to be the method of choice for determination of intragastric pH in patients at risk for stress gastric ulcers in the medical ICU.

Adult↗
PubMed1993

Clarithromycin for the eradication of Helicobacter pylori.

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15%. Clarithromycin has potential advantages over other macrolides to which H. pylori is susceptible because of its acid stability and solubility at low pH. We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H. pylori-infected patients. The 13C-urea breath test was used to evaluate the effectiveness of therapy. Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment. H. pylori was eradicated in five (42%) of 12 patients. Adverse events were intermittent and mild. Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H. pylori.

Adolescent↗
PubMed1993

Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants.

The fractional synthesis rate (FSR) of cholesterol was measured in 6 breast-fed and 12 formula-fed infants (ages 4 to 5 months) using the 2H2O method. The breast-fed infants had higher cholesterol intakes (18.2 +/- 4.0 vs. 3.4 +/- 1.8 mg/kg per day, P = 0.001), plasma total cholesterol (183 +/- 47 vs. 112 +/- 22 mg/dl, P = 0.013), and plasma low density lipoprotein (LDL)-cholesterol (83 +/- 26 vs. 48 +/- 16 mg/day, P = 0.023) than the formula-fed infants (6.9 +/- 2.6 vs. 2.1 +/- 0.6%/day, P < 0.001). Among all infants, there was a significant inverse relationship (P = 0.002, r = 0.66) between the FSR of cholesterol and dietary cholesterol intake. Our findings indicate that the greater cholesterol intake of the breast-fed infants was associated with elevated plasma LDL-cholesterol concentrations and that cholesterol synthesis in human infants may be efficiently regulated via HMG-CoA reductase when infants are challenged with high intakes of dietary cholesterol.

Breast Feeding↗
PubMed1991

Water source as risk factor for Helicobacter pylori infection in Peruvian children. Gastrointestinal Physiology Working Group.

Helicobacter pylori infection is widespread among Peruvian adults by the age of 30, but the age at which children become infected, the prevalence of disease, and the role of socioeconomic status in the epidemiology of infection are not known. We used the 13C-urea breath test to study the prevalence of infection in 407 Peruvian children from Lima, aged 2 months to 12 years, from families of low and high socioeconomic status. Peruvian children acquire H pylori early in life and the number of infected individuals increases rapidly with age; overall prevalence was 48%. H pylori infection was independent of sex, but was highly correlated with socioeconomic status; prevalence of infection was higher among children from low-income families than among those from high-income families (56% vs 32%, p = 0.001). Children whose homes had external water sources were three times more likely to be infected than were those whose homes had internal water sources. Among families with internal water sources, there was no difference in H pylori infection associated with income. Children from high-income families whose homes were supplied with municipal water were 12 times more likely to be infected than were those from high-income families whose water supply came from community wells. The findings show that the prevalence of H pylori infection is high among young Peruvian children and that the municipal water supply seems to be an important source of infection among Lima children from families of both low and high socioeconomic status.

Age Factors↗
PubMed1990

Antimony electrodes. Mucosal potential differences and buffer composition adversely affect pH measurements in the stomach.

Antimony electrodes are clinically useful because of their low cost and simple construction; they have no glass to break. There is only a few hundred ohms resistance between an antimony pH electrode and the reference electrode so that the voltage generated can be recorded with simple low-impedance recorders linked to microcomputers. We used antimony pH electrodes with silver-silver chloride electrodes applied to the skin to measure the gastric pH in vivo and obtained erroneously high values. Using an ion-permeable dialysis chamber to surround electrodes in vivo, we showed that the discrepancy was caused by interference from gastric transmucosal potential difference. To circumvent the interference, we used a combination electrode constructed by embedding a monocrystalline antimony electrode and a silver-silver chloride reference electrode in dental acrylic. Antimony pH electrodes calibrated with commercial pH buffers also gave erroneous readings in HCl solutions of known pH. The erroneous readings were due, in part, to organic complex-forming ligands or organic salts such as potassium phthalate present in commercial buffer solutions. Accurate pH calibration can be obtained with citrate or acetate buffers or by using a normogram to correct for the errors introduced with commercial buffers. The combination antimony pH electrode has a number of potential clinical and research applications and simplifies obtaining accurate and reliable pH data in vivo.

Antimony↗
PubMed1989

Sensitivity of the esophageal mucosa to pH in gastroesophageal reflux disease.

To determine the relation between the sensation of pain in gastroesophageal reflux and the pH of the refluxate, we studied 25 individuals with symptomatic gastroesophageal reflux and positive Bernstein tests. We quantitatively assessed the sensitivity of the esophageal mucosa to pain associated with the intraesophageal infusion of eight different HCl solutions (pH 1, 1.5, 2, 2.5, 3, 4, 5, and 6). Test solutions were infused at 8 ml/min through an eight-lumen catheter with the orifices placed 5 cm above the lower esophageal sphincter. Each subject received all eight solutions in a double-blind randomized fashion. The time-to-pain onset increased with increasing pH; i.e., there was a highly significant difference between the time-to-pain and pH (p less than 0.001), with the time-to-pain significantly longer with increasing pH (r = 0.77). In addition to more rapid onset of pain, all subjects experienced pain with the pH 1 and 1.5 solutions, 80% had pain with the pH 2.0 solution, and half had pain with solutions of pH 2.5-6. Fifteen of these subjects underwent 24-h pH monitoring and these tests were examined for factors associated with pain. Only 64% of all pain episodes were associated with a pH drop of less than 4; the lowest pH obtained was not different between episodes with and without pain. Reflux episodes resulting in pain were significantly longer than those without pain and were more often associated with a recently preceding painful episode. Overall, none of the data from the 24-h pH monitoring was useful for predicting pain. The acid infusion studies and the 24-h pH data, taken together, suggest episodes of pain sensitize the patient for subsequent pain.

Adult↗
PubMed1989

In vivo susceptibility of Campylobacter pylori.

Campylobacter pylori infection has been associated with duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia. Although in vitro studies have shown that C. pylori is susceptible to most commonly used antibiotics, predictions from in vitro sensitivity studies have not led to a safe and generally effective therapy; C. pylori has proved to be very difficult to eradicate in vivo. We used the urea breath test to assess the susceptibility of C. pylori in vivo to various drugs. C. pylori was susceptible to bismuth subsalicylate, bismuth subnitrate, and furazolidone. C. pylori was not susceptible (i.e., urease activity remained despite administration of the drug) to the following drugs: 1) antiulcer agents (cimetidine, ranitidine, famotidine, omeprazole, misoprostol, sucralfate, liquid antacids); 2) NSAIDs (aspirin, indomethacin, ibuprofen, naproxen, tolmetin); 3) antibiotics (oral penicillin V, trimethoprim-sulfamethoxazole, dicloxacillin); 4) salts (lithium, ferrous sulfate, gold); 5) miscellaneous (acetaminophen, phenytoin, hydrochlorothiazide, propranolol, metoprolol, metoclopramide, ursodeoxycholic acid). Oral antimicrobials can be administered directly onto the site of infection, so that a very low oral dose will provide many multiples of the in vitro minimal inhibitory concentration. Furazolidone suspension (7 mg) was administered seven times daily (daily dose 49 mg) to three individuals infected by C. pylori during suppression of gastric acid secretion with famotidine (40 mg bid). After 4 days, all subjects had significant reductions in urease activity (two to normal and one to a borderline value). This response suggested that very low-dose therapy may be useful either alone or combined with bismuth. Conclusive establishment of an etiologic (or major contributory) relationship of C. pylori to ulcer disease will require a safe and reliable method to eradicate the organism from the stomach and duodenum.

Anti-Bacterial Agents↗
PubMed1988

Spicy food and the stomach. Evaluation by videoendoscopy.

We used videoendoscopy to investigate the effect of eating spicy foods on the gastric mucosa. We employed four meals: a bland meal of unpeppered steak and french fries (negative control), a bland meal with 1950 mg of aspirin (positive control), a spicy Mexican meal (30 g of jalapeño peppers), and a pepperoni pizza. Twelve subjects (eight men and four women, aged 24 to 43 years) were studied in a randomized, crossover trial with the test meal given at the noon and evening meals; each subject received all four test meals. Each study consisted of a baseline endoscopy, which was repeated approximately 12 hours after the last test meal. Gastric and duodenal damage was scored using a modification of the Lanza scale. Eleven of 12 individuals taking the bland meal plus aspirin developed multiple gastric erosions (median score, C; which equates with "severe" injury). In contrast, the median endoscopic score for the other three meals was 0. Single cases of a single erosion were present after the Mexican meals and after the pizza meals. Another experiment was done to examine the effect of spices directly on the gastric mucosa; approximately 30 g of fresh jalapeño peppers was ground in a food processor and then placed directly into the stomach. Endoscopy after 24 hours revealed no visible mucosal damage. The ingestion of highly spiced meals by normal individuals is not associated with endoscopically demonstrable gastroduodenal mucosal damage.

Adult↗
PubMed1988

Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease.

We studied the frequency of active Campylobacter pylori infection in persons from North America (n = 53) or the People's Republic of China (n = 15) who had no gastrointestinal symptoms or a history of ulcer disease and in patients with active or recently active duodenal or gastric ulcers diagnosed by endoscopy (n = 105). C. pylori infection was significantly (P less than .001) more frequent in patients with peptic ulcers (88%) than in the normal group (45%). An age-related increase in the frequency of C. pylori infection in subjects with no gastrointestinal symptoms paralleled the known age-related increase in prevalence of gastritis. The frequency of C. pylori infection in patients with duodenal ulcers was greater than 80%, irrespective of age. C. pylori infection was more common in the Chinese group (age, 20-39 y) than in the North American group of the same age (60% vs. 24%). Association of C. pylori with specific diseases should not be inferred without knowing the prevalence of C. pylori infection in reference populations of the same age and ethnic background.

Adult↗