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April 2000
5605
EFFECTS OF AMTOLMETIN GUACYL VERSUS PLACEBO AND
MISOPROSTOL ON GASTRIC EMPTYING IN HEALTHY VOL-
UNTEERS.
Marisa Chiloiro, Giuseppe Riezzo, I R C C S S De Bellis. Castellana G,
Italy.
Prostaglandins regulate gastric motor function. The results of experimental
studies support the hypothesis that decreased prostaglandin production
might play a part in the gastric mucosal injury induced by alcohol.
Moreover inhibition of prostaglandins by nonsteroidal antiinflammatory
drugs (NSAlDs) may alter gastric emptying. Aim: to verify the protective
effects of amtolmetin guacyl (AMG) in comparison with a protective
reference drug (misoprostol) and placebo from alcohol induced stomach
damage we evaluated gastric emptying (GE) after alcohol ingestion. Pa-
tients and Metods: Twenty-four healthy volunteers entered a double-blind.
randomised, placebo-controlled, crossover study. Twelve subjects assumed
400 ml of orange juice with alcohol (12 % v/v) after four days of placebo,
AMG (1200 mg/die) or misoprostol (400JLg/die). During each session.
gastrointestinal symptom score ranging from 0 (absent) to 3 (severe) was
recorded. Gastric emptying was evaluated using an ultrasonographic
method (Esaote AU 530. Ansaldo, Italy). The dimensions of the antrum
were recorded before and after the test meal, at 10 minute intervals for 180
min. The final emptying time (FI'), the half time and the area under the
curve (AUC) of gastric emptying were assessed and MANOVA was
porformed. Results: no differences were found in symptom score among
the three pre-treatments. The FI' following pretreatment with placebo was
significantly longer than the FI' following pretreatment with misoprostol
(I 39.4:!:24.6 vs 105.8 :!: 15.0 MANOVA: p<O.OI; multiple comparisons:
p<O.OI). No differences were found in the AUC among the three pretreat-
ments (placebo, AMG, rnisoprostol: 1735.5 :!:760.5, 1677.5 :!: 754.3,
136.9 :!:616.8, respectively). Conclusions: the GE rate is delayed after
alcohol and placebo administration. Misoprostol significantly reduced the
alcohol-induced GE delayed; amtolmetin guacyl although behaving simi-
larly to misoprostol, did not reach statistical significance in this model. The
effect of AMG (NSAIDs) on GE is similar than misoprostol. Therefore,
this findings confirmed the protective effect of AMG even in presence of
an injurious agent to gastric mucosa such as alcohol.
5606
MOSAICISM IN VACA ALLELIC TYPES OF H. PYLORI IN KO-
REAN CHILDREN AND CLINICAL CORRELATION.
Yon Ho Choe, Tae Sook Hwang, Inha Univ Hosp, Inchon, South Korea.
The purposes of this study are to characterize the vaeA alleles that are
present in different strains of H. pylori in Korean children, and to deter-
mine whether there is a correlation between particular vacA slm genotypes
and clinical outcome. Antral biopsy specimens from 34 patients with H.
pylori infection were used for analysis. They included 22 H. pylori-positive
patients with iron-deficiency anemia (IDA), 10 without IDA, and 2 with
duodenal ulcer. Biopsy specimens, stored at -70°C, were homogenized in
300 JLL of proteinase K solution. DNA was isolated from the homogenate
by extraction with phenollchloroform and ethanol precipitation. PCR prim-
ers for sl, s2, ml (mlb), m2, eagA, ieeAl, and ieeA2 were used in this
study. In case sl was positive, the DNA sequence was determined with the
dideoxynucleotide chain-termination method using an ABI PRISM 310
Genetic Analyzer (Perkin Elmer, USA) with BigDye Terminator Cycle
Sequencing Kit to identify sla, sib, and slc. We analyzed vaeA genotypic
differences to determine whether the particular vacA genotype is related to
the occurrence of antral gastritis with or without IDA, or peptic ulcer. In
results, 30 (88.2%) were sl, and 4 (1.8%) were s2. Of these thirty sl
subjects, 14 were sIa, none was slb, 15 were slc, and one was s1als1c
hybrid type. Twenty-two were mI (m1b), and 5 were m2. CagA was found
in 9.2% (31134), ieeAl in 52.9% (18/34), and ieeA2 in 14.7% (5/34).
There was no significant association between any vaeA genotype and
disease in Korean children. The ieeA allelic type was independent of the
eagA and vaeA status. In some specific regions, Korean strains showed
different sequences from those of western strains: GGGAGCGTTR for s1a,
and GGGGYTATTG for sic. Among Korean H. pylori strains vaeA alleles
with all combinations of signal sequence and mid-region type were found,
with the exception of s2/ml and types including sIb. Slc/ml and slalml
were major types in Korea. Specific method such as PCR-reverse hybrid-
ization using allele-specific probes indigenous to each country is needed
for the accurate identification of the various vaeA allelic types because of
the diverse geographic distribution.
AGAA1223
5607
PRE· AND POST·ENDOSCOPY PEPSINOGEN I IN SERUM.
Lucia Clara, Ulrich Peitz, Andreas Leodolter, Stefan Kahl, Peter Malfer-
theiner, Univ of Magdeburg, Magdeburg, Germany.
Background: Pepsinogen I levels in serum are inversely related to gastric
atrophy. In a previous study we found a high interindividual variability of
pepsinogen I unexplained by the grade of atrophy. It seemed that serum
samples taken after endoscopy tended to be higher. Aim: To test the
hypothesis that pepsinogen I in serum is enhanced through upper gastro-
intestinal endoscopy including biopsies. Methods and Patients: In n=48
(34 male; age mean 53 years; range 20-83 y.) consecutive patients under-
going upper GI endoscopy we collected serum samples just before and
immediately after endoscopy. Pepsinogen I was measured by ELISA
(Gastroset POI, Orion Diagnostic, Finland) Helicobacter pylori status was
determined by rapid urease test, histology and culture. Statistic tests:
Kolmogorov-Smirnov test for normal distrubution, t-test for paired and
unpaired samples. Results: The mean value of pepsinogen I in serum before
gastroscopy was 87,8 :!:52,8 (SO) JLg/I (range 16,4 to 225,4 JLglI), whereas
the mean value after gastroscopy was significantly (p<O,OI) lower with
78,8 ± 46,6 JLg/I (range 13,5 to 221,2 JLglI). The mean difference (pre
minus post) was 8,9 :!: 12,0 JLglI (range -25,4 to 42,8 JLg/I). The Helico-
bacter pylori infection rate in the whole group was 28,8%. Both, pre- and
post-endoscopy pepsinogen I, were not correlated with age, Helieobaeter
pylori infection or sex. Patients taking proton pump inhibitors showed
significantly (p<0,02) higher pepsinogen J levels (mean 140,6 J.LglI) vs.
those without PPJ therapy (mean 80,1 J.LglI). Conclusions: Pepsinogen I is
not enhanced through the endoscopic procedure. The reason for the slight
decrease of pepsinogen I after upper GI endoscopy remains elusive. PPI
treatment is another important factor for pepsinogen I variability in clinical
trials.
5608
BLOOD LEVELS OF FURAZOLIDONE IN PATIENTS ON
ANTI-H. PYLORI THERAPY.
Luiz G. Coelho, Silvana A. Calafatti, Washington L. Vieira, Rita S. Barros,
Polyana E. Casaes, Rosana B. Morais, Julienne M. Borges, Maria L.
Fernandes, Rodrigo M. Ortiz, Jose Pedrazzoli-Jr, Luiz P. Castro, Fed Univ
of Minas Gerais, Belo Horizonte, Brazil; Univ of CA, San Francisco,
Braganca, Brazil; Sao Francisco Univ, Braganca, Brazil.
Furazolidone, a low-cost synthetic nitrofuran derivative is largely used in
South America and China for H. pylori eradication. Only limited informa-
tion is available concerning its pharmacokinetics in humans. Aim: To
monitor blood levels of furazolidone during H. pylori therapy with fura-
zolidone associated to antimicrobials. Patients and methods: We evaluated
62 (40 M, 22 F, median age 41.5 years) H. pylori positive DU patients
using three different therapeutic schedules. Blood samples were collected
before, during and one day after the end of the treatment. The serum
furazolidone levels were determined by by HPLC. The lowest limit of
detection was 0.01J.Lg/mL with a precision of 9% from peak height and an
average recovery of 92%. Statistics: Chi-square test, Kruskal-Wallis and
Wilcoxon test. Results: There was no difference between the three groups
concerning furazolidone concentrations (Table). Adverse effects were
more common in Group 2 (p =0.004). Conclusions: Furazolidone is poorly
absorved and/or rapidly and extensively metabolized. Adverse effects do
not correlate with blood levels during H. pylori therapy.
Blood furazolidone concentrations Inthethree groups
Group Time Mean Median SO Min Max p
(flglmL) (rg/mL)
1 Middle 0067 0.00 0159 0.00 061 089
(n=24) End 0068 0.00 0.195 0.00 0.85
2 Middle 0036 0.00 0080 0.00 0.31 079
(n=17) End 0025 000 0049 0.00 016
3 Middle 0120 000 0.175 0.00 0.67 0.12
(n=21) End 0.071 0.00 0157 0.00 0.71
Group 1:Lanzoprazole (L)+ clarithromycin (C)+ furazolidone (F). for7days.
Group 2:L+C+F+ colloidal bismuth subcitrate (CBS). for7 days.
Group 3:L+C+F + CBS. for14days
ml
m2
sla
10
2
slb stc
12
1
52
o
2

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Coelho2000 los niveles en sangre de furazolidona en pacientes en anti h. pylori terapia

  • 1. April 2000 5605 EFFECTS OF AMTOLMETIN GUACYL VERSUS PLACEBO AND MISOPROSTOL ON GASTRIC EMPTYING IN HEALTHY VOL- UNTEERS. Marisa Chiloiro, Giuseppe Riezzo, I R C C S S De Bellis. Castellana G, Italy. Prostaglandins regulate gastric motor function. The results of experimental studies support the hypothesis that decreased prostaglandin production might play a part in the gastric mucosal injury induced by alcohol. Moreover inhibition of prostaglandins by nonsteroidal antiinflammatory drugs (NSAlDs) may alter gastric emptying. Aim: to verify the protective effects of amtolmetin guacyl (AMG) in comparison with a protective reference drug (misoprostol) and placebo from alcohol induced stomach damage we evaluated gastric emptying (GE) after alcohol ingestion. Pa- tients and Metods: Twenty-four healthy volunteers entered a double-blind. randomised, placebo-controlled, crossover study. Twelve subjects assumed 400 ml of orange juice with alcohol (12 % v/v) after four days of placebo, AMG (1200 mg/die) or misoprostol (400JLg/die). During each session. gastrointestinal symptom score ranging from 0 (absent) to 3 (severe) was recorded. Gastric emptying was evaluated using an ultrasonographic method (Esaote AU 530. Ansaldo, Italy). The dimensions of the antrum were recorded before and after the test meal, at 10 minute intervals for 180 min. The final emptying time (FI'), the half time and the area under the curve (AUC) of gastric emptying were assessed and MANOVA was porformed. Results: no differences were found in symptom score among the three pre-treatments. The FI' following pretreatment with placebo was significantly longer than the FI' following pretreatment with misoprostol (I 39.4:!:24.6 vs 105.8 :!: 15.0 MANOVA: p<O.OI; multiple comparisons: p<O.OI). No differences were found in the AUC among the three pretreat- ments (placebo, AMG, rnisoprostol: 1735.5 :!:760.5, 1677.5 :!: 754.3, 136.9 :!:616.8, respectively). Conclusions: the GE rate is delayed after alcohol and placebo administration. Misoprostol significantly reduced the alcohol-induced GE delayed; amtolmetin guacyl although behaving simi- larly to misoprostol, did not reach statistical significance in this model. The effect of AMG (NSAIDs) on GE is similar than misoprostol. Therefore, this findings confirmed the protective effect of AMG even in presence of an injurious agent to gastric mucosa such as alcohol. 5606 MOSAICISM IN VACA ALLELIC TYPES OF H. PYLORI IN KO- REAN CHILDREN AND CLINICAL CORRELATION. Yon Ho Choe, Tae Sook Hwang, Inha Univ Hosp, Inchon, South Korea. The purposes of this study are to characterize the vaeA alleles that are present in different strains of H. pylori in Korean children, and to deter- mine whether there is a correlation between particular vacA slm genotypes and clinical outcome. Antral biopsy specimens from 34 patients with H. pylori infection were used for analysis. They included 22 H. pylori-positive patients with iron-deficiency anemia (IDA), 10 without IDA, and 2 with duodenal ulcer. Biopsy specimens, stored at -70°C, were homogenized in 300 JLL of proteinase K solution. DNA was isolated from the homogenate by extraction with phenollchloroform and ethanol precipitation. PCR prim- ers for sl, s2, ml (mlb), m2, eagA, ieeAl, and ieeA2 were used in this study. In case sl was positive, the DNA sequence was determined with the dideoxynucleotide chain-termination method using an ABI PRISM 310 Genetic Analyzer (Perkin Elmer, USA) with BigDye Terminator Cycle Sequencing Kit to identify sla, sib, and slc. We analyzed vaeA genotypic differences to determine whether the particular vacA genotype is related to the occurrence of antral gastritis with or without IDA, or peptic ulcer. In results, 30 (88.2%) were sl, and 4 (1.8%) were s2. Of these thirty sl subjects, 14 were sIa, none was slb, 15 were slc, and one was s1als1c hybrid type. Twenty-two were mI (m1b), and 5 were m2. CagA was found in 9.2% (31134), ieeAl in 52.9% (18/34), and ieeA2 in 14.7% (5/34). There was no significant association between any vaeA genotype and disease in Korean children. The ieeA allelic type was independent of the eagA and vaeA status. In some specific regions, Korean strains showed different sequences from those of western strains: GGGAGCGTTR for s1a, and GGGGYTATTG for sic. Among Korean H. pylori strains vaeA alleles with all combinations of signal sequence and mid-region type were found, with the exception of s2/ml and types including sIb. Slc/ml and slalml were major types in Korea. Specific method such as PCR-reverse hybrid- ization using allele-specific probes indigenous to each country is needed for the accurate identification of the various vaeA allelic types because of the diverse geographic distribution. AGAA1223 5607 PRE· AND POST·ENDOSCOPY PEPSINOGEN I IN SERUM. Lucia Clara, Ulrich Peitz, Andreas Leodolter, Stefan Kahl, Peter Malfer- theiner, Univ of Magdeburg, Magdeburg, Germany. Background: Pepsinogen I levels in serum are inversely related to gastric atrophy. In a previous study we found a high interindividual variability of pepsinogen I unexplained by the grade of atrophy. It seemed that serum samples taken after endoscopy tended to be higher. Aim: To test the hypothesis that pepsinogen I in serum is enhanced through upper gastro- intestinal endoscopy including biopsies. Methods and Patients: In n=48 (34 male; age mean 53 years; range 20-83 y.) consecutive patients under- going upper GI endoscopy we collected serum samples just before and immediately after endoscopy. Pepsinogen I was measured by ELISA (Gastroset POI, Orion Diagnostic, Finland) Helicobacter pylori status was determined by rapid urease test, histology and culture. Statistic tests: Kolmogorov-Smirnov test for normal distrubution, t-test for paired and unpaired samples. Results: The mean value of pepsinogen I in serum before gastroscopy was 87,8 :!:52,8 (SO) JLg/I (range 16,4 to 225,4 JLglI), whereas the mean value after gastroscopy was significantly (p<O,OI) lower with 78,8 ± 46,6 JLg/I (range 13,5 to 221,2 JLglI). The mean difference (pre minus post) was 8,9 :!: 12,0 JLglI (range -25,4 to 42,8 JLg/I). The Helico- bacter pylori infection rate in the whole group was 28,8%. Both, pre- and post-endoscopy pepsinogen I, were not correlated with age, Helieobaeter pylori infection or sex. Patients taking proton pump inhibitors showed significantly (p<0,02) higher pepsinogen J levels (mean 140,6 J.LglI) vs. those without PPJ therapy (mean 80,1 J.LglI). Conclusions: Pepsinogen I is not enhanced through the endoscopic procedure. The reason for the slight decrease of pepsinogen I after upper GI endoscopy remains elusive. PPI treatment is another important factor for pepsinogen I variability in clinical trials. 5608 BLOOD LEVELS OF FURAZOLIDONE IN PATIENTS ON ANTI-H. PYLORI THERAPY. Luiz G. Coelho, Silvana A. Calafatti, Washington L. Vieira, Rita S. Barros, Polyana E. Casaes, Rosana B. Morais, Julienne M. Borges, Maria L. Fernandes, Rodrigo M. Ortiz, Jose Pedrazzoli-Jr, Luiz P. Castro, Fed Univ of Minas Gerais, Belo Horizonte, Brazil; Univ of CA, San Francisco, Braganca, Brazil; Sao Francisco Univ, Braganca, Brazil. Furazolidone, a low-cost synthetic nitrofuran derivative is largely used in South America and China for H. pylori eradication. Only limited informa- tion is available concerning its pharmacokinetics in humans. Aim: To monitor blood levels of furazolidone during H. pylori therapy with fura- zolidone associated to antimicrobials. Patients and methods: We evaluated 62 (40 M, 22 F, median age 41.5 years) H. pylori positive DU patients using three different therapeutic schedules. Blood samples were collected before, during and one day after the end of the treatment. The serum furazolidone levels were determined by by HPLC. The lowest limit of detection was 0.01J.Lg/mL with a precision of 9% from peak height and an average recovery of 92%. Statistics: Chi-square test, Kruskal-Wallis and Wilcoxon test. Results: There was no difference between the three groups concerning furazolidone concentrations (Table). Adverse effects were more common in Group 2 (p =0.004). Conclusions: Furazolidone is poorly absorved and/or rapidly and extensively metabolized. Adverse effects do not correlate with blood levels during H. pylori therapy. Blood furazolidone concentrations Inthethree groups Group Time Mean Median SO Min Max p (flglmL) (rg/mL) 1 Middle 0067 0.00 0159 0.00 061 089 (n=24) End 0068 0.00 0.195 0.00 0.85 2 Middle 0036 0.00 0080 0.00 0.31 079 (n=17) End 0025 000 0049 0.00 016 3 Middle 0120 000 0.175 0.00 0.67 0.12 (n=21) End 0.071 0.00 0157 0.00 0.71 Group 1:Lanzoprazole (L)+ clarithromycin (C)+ furazolidone (F). for7days. Group 2:L+C+F+ colloidal bismuth subcitrate (CBS). for7 days. Group 3:L+C+F + CBS. for14days ml m2 sla 10 2 slb stc 12 1 52 o 2