Triple therapy with sucralfate, amoxycillin and metronidazole for healing duodenal ulcer and eradicating Helicobacter pylori infection.

METHODS: Seventy-seven chronic duodenal ulcer patients (50 male) were entered into this study. Treatment was started with sucralfate suspension (2 g b.d.) for 8 weeks. After 2 weeks the patients also received 750 mg amoxycillin t.d.s. plus 500 mg metronidazole t.d.s. for 12 days. Endoscopy with six antral biopsies (urease test, Gram staining, culture and histology) was performed before commencement of sucralfate therapy, 4 weeks after the end of antibiotic therapy, and during the follow-up examinations at 6 and 12 months. RESULTS: Seven patients were excluded prematurely from the study. Helicobacter pylori in five patients had primary resistance to metronidazole and these patients were also excluded. The ulcer healing rate 4 weeks after the end of antibiotic therapy was 92% and the H. pylori eradication rate was 82% (all per protocol). In all patients who were still H. pylori-positive, the bacterium became resistant to metronidazole and histologically the inflammatory state of the mucosa was the same as before treatment. All H. pylori-eradicated patients (n = 53) were re-examined after 6 and 12 months; no ulcer recurrence was observed and each time only one reinfection was found. CONCLUSIONS: In an open study, sucralfate with amoxycillin and metronidazole appeared to act together to eradicate H. pylori infection and to speed duodenal ulcer healing.

A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking.

Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí Health Aging Study (BHAS).

Apolipoprotein E (ApoE) polymorphism influences lipid metabolism, but its association with arterial hypertension is controversial. The objective of this study was to examine the association between ApoE polymorphism and prevalent hypertension in a large unselected population of older adults. Participants from the baseline of the Bambuí Health Aging Study whose ApoE genes had been genotyped were selected for this study (N = 1406, aged 60-95 years). These subjects represented 80.7% of the total elderly residents in Bambuí city, MG, Brazil. Hypertension was defined as a systolic blood pressure > or =140 mmHg and/or a diastolic blood pressure > or =90 mmHg, or the use of anti-hypertensive medication. The exposure variable was the ApoE genotype as follows: epsilon3 carriers, epsilon3epsilon3; epsilon2 carriers, epsilon2epsilon2 or epsilon2epsilon3, and epsilon4 carriers, epsilon3epsilon4 or epsilon4epsilon4. Potential confounding variables were age, gender, traditional cardiovascular risk factors, uric acid, and creatinine levels. The prevalence of hypertension was 61.3%. Compared with the epsilon3 homozygotes, neither the epsilon2 nor the epsilon4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95%CI = 0.83-1.07 and 0.98, 0.89-1.07, respectively). On the other hand, the epsilon2 allele carriers had lower LDL cholesterol levels (P < 0.001) and the epsilon4 carriers had higher LDL cholesterol levels (P = 0.036). This study provides epidemiologic evidence that the ApoE genotype is not associated with prevalent hypertension in old age.

Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambuí Health and Aging Study.

Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. The objective of the present study was to assess ApoE allele and genotype distribution in a large elderly community-based sample and its association with age, sex and skin color. Participants included 1408 subjects (80.8% of all residents aged (3)60 years) residing in Bambuí city, MG, Brazil. The DNA samples were subjected to the polymerase chain reaction amplification, followed by the restriction fragment length polymorphism technique, with digestion by HhaI. Analysis was carried out taking into consideration the six ApoE genotypes (e3/e3, e3/e4, e2/e3, e4/e4, e2/e4, and e2/e2), the three ApoE alleles, and the number of ApoE4 alleles for each individual. The e3 allele predominated (80.0%), followed by e4 (13.5%) and e2 (6.5%). All six possible genotypes were observed, the e3/e3 genotype being the most frequent (63.4%). This distribution was similar to that described in other western populations. Sex was not associated with number of ApoE4 alleles. Black skin color was significantly and independently associated with the presence of two ApoE4 alleles (age-sex adjusted OR = 7.38; 95%CI = 1.93-28.25), showing that the African-Brazilian elderly have a high prevalence of the e4 allele, as observed in blacks from Africa. No association between number of ApoE4 alleles and age was found, suggesting the absence of association of ApoE genotype with mortality in this population.

[Cytodiagnosis of the stomach: a comparative survey of cytological and histological investigations (author's transl)]. / Zur Zytodiagnostik des Magens. Vergleichende zytologische und histologische Untersuchungen.

The consideration was the center of our comparative survey: early diagnosis of gastric cancer by combination of gastroscopy, gastrobiopsy and gastrocytology. We are filled with dismay that this simple method is not yet used in every case of wellfounded suspicion of gastric cancer. In our own material cytological findings of cancer could be proved in 88% and verified histologically. 2% of cytological diagnosis were false negative because the brush samples were not taken from the right location by the gastroscopists. Simultaneously with the evaluation of the dignity, a diagnosis of the different forms of gastritis was made. A vast conformity with pathohistological results could be achieved. In stenosing processes of the stomach and also in diagnosis of lesions in the cardia, the use of a cell brush would be of great advantage toward gastrobiopsy.

Kinetics of specific IgG antibodies for monitoring the effect of anti-Helicobacter pylori chemotherapy.

A total of 104 patients with recurrent duodenal ulcer were treated with either ranitidine plus amoxicillin plus metronidazole or ranitidine plus placebo. To study the effect of the eradication of Helicobacter pylori on the systemic immune response in an IgG ELISA, sera were drawn from all patients before the onset of therapy and at 6, 16 +/- 2, 32 +/- 2, and 60 +/- 2 weeks after therapy. In patients with eradication of the organism, a significant (P < .001) reduction of the specific IgG titer occurred. This was not observed in patients without bacterial eradication. If a titer reduction of > 50% was taken as an indicator for eradication of H. pylori, the sensitivity of the serologic test was 97.6%-99.7%. Its specificity increased with the interval to the onset of chemotherapy from 56.3% to 97.6%. Serologic tests are simple to perform and cause very little discomfort to the patient.

Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer.

BACKGROUND: Persistent infection with Helicobacter pylori is associated with the recurrence of duodenal ulcer. Whether the efficacy of bismuth therapy in reducing the rate of recurrence of duodenal ulcer is due to its antimicrobial effects on H. pylori or to a direct protective action on the mucosa is still a matter of debate. METHODS: To study the effect of the eradication of H. pylori on the recurrence of duodenal ulcer, we treated 104 patients with H. pylori infection and recurrent duodenal ulcer with either amoxicillin (750 mg three times daily) plus metronidazole (500 mg three times daily) or identical-appearing placebos, given orally for 12 days. All patients also received ranitidine (300 mg each night) for 6 or 10 weeks. Endoscopy was performed before treatment and periodically during follow-up for up to 12 months after healing. RESULTS: Among the 52 patients given antibiotics, H. pylori was eradicated in 46, as compared with 1 of the 52 given placebo (89 percent vs. 2 percent, P < 0.001). After six weeks, the ulcers were healed in 48 patients given antibiotics and 39 given placebo (92 percent vs. 75 percent, P = 0.011). Side effects, mainly diarrhea, occurred in 15 percent of the patients given antibiotics. Among the patients followed up for 12 months, duodenal ulcers recurred in 4 of 50 patients given antibiotics and 42 of 49 given placebo (8 percent vs. 86 percent, P < 0.001). Ulcers recurred in 1 of 46 patients in whom H. pylori had been eradicated, as compared with 45 of 53 in whom H. pylori persisted (2 percent vs. 85 percent, P < 0.001). CONCLUSIONS: In patients with recurrent duodenal ulcer, eradication of H. pylori by a regimen that does not have any direct action on the mucosa is followed by a marked reduction in the rate of recurrence, suggesting a causal role for H. pylori in recurrent duodenal ulcer.

Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction.

Smoking behavior is influenced by genetic factors. Polymorphisms affecting the dopaminergic system have been linked to smoking habits. The aim of this study was to investigate if the T102C polymorphism of the 5-HT(2A) receptor gene is related to tobacco use, since this receptor modulates the mesolimbic dopamine system and the C allele is associated with reduced receptor gene expression. A sample of 625 subjects were genotyped and classified according to their smoking behavior (never, former, or current smokers). We found differences in the distribution of the genotypes when the current smokers were compared with the never + former smokers, suggesting that T102C polymorphism is associated with maintenance, but not with initiation of the smoking habit. The CC genotype was more frequent in the current smokers than in the never + former smokers (chi(2) = 6.825, P = 0.03). The odds ratio of being a current smoker with a CC genotype was 1.63, 95% CI 1.06-2.51.

Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí Health Aging Study (BHAS)

Apolipoprotein E (ApoE) polymorphism influences lipid metabolism, but its association with arterial hypertension is controversial. The objective of this study was to examine the association between ApoE polymorphism and prevalent hypertension in a large unselected population of older adults. Participants from the baseline of the Bambuí Health Aging Study whose ApoE genes had been genotyped were selected for this study (N = 1406, aged 60-95 years). These subjects represented 80.7 percent of the total elderly residents in Bambuí city, MG, Brazil. Hypertension was defined as a systolic blood pressure ³140 mmHg and/or a diastolic blood pressure ³90 mmHg, or the use of anti-hypertensive medication. The exposure variable was the ApoE genotype as follows: e3 carriers, e3e3; e2 carriers, e2e2 or e2e3, and e4 carriers, e3e4 or e4e4. Potential confounding variables were age, gender, traditional cardiovascular risk factors, uric acid, and creatinine levels. The prevalence of hypertension was 61.3 percent. Compared with the e3 homozygotes, neither the e2 nor the e4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95 percentCI = 0.83-1.07 and 0.98, 0.89-1.07, respectively). On the other hand, the e2 allele carriers had lower LDL cholesterol levels (P < 0.001) and the e4 carriers had higher LDL cholesterol levels (P = 0.036). This study provides epidemiologic evidence that the ApoE genotype is not associated with prevalent hypertension in old age.

Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambuí Health and Aging Study

Apolipoprotein E (ApoE) is one of the most extensively studied genes in the context of aging, but there are few population-based studies on ApoE polymorphism in the elderly in developing countries. The objective of the present study was to assess ApoE allele and genotype distribution in a large elderly community-based sample and its association with age, sex and skin color. Participants included 1408 subjects (80.8 percent of all residents aged ³60 years) residing in Bambuí city, MG, Brazil. The DNA samples were subjected to the polymerase chain reaction amplification, followed by the restriction fragment length polymorphism technique, with digestion by HhaI. Analysis was carried out taking into consideration the six ApoE genotypes (e3/e3, e3/e4, e2/e3, e4/e4, e2/e4, and e2/e2), the three ApoE alleles, and the number of ApoE4 alleles for each individual. The e3 allele predominated (80.0 percent), followed by e4 (13.5 percent) and e2 (6.5 percent). All six possible genotypes were observed, the e3/e3 genotype being the most frequent (63.4 percent). This distribution was similar to that described in other western populations. Sex was not associated with number of ApoE4 alleles. Black skin color was significantly and independently associated with the presence of two ApoE4 alleles (age-sex adjusted OR = 7.38; 95 percentCI = 1.93-28.25), showing that the African-Brazilian elderly have a high prevalence of the e4 allele, as observed in blacks from Africa. No association between number of ApoE4 alleles and age was found, suggesting the absence of association of ApoE genotype with mortality in this population.