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Biomedical subjects

T Gilat

Publications and source records attributed to T Gilat.

At least 19 recordsLinked to original sources

Halitosis and Helicobacter pylori. A possible link?

The exact pathophysiological mechanism of halitosis is not clear, and in many patients the etiology is an enigma. We followed three couples in which one member or both had halitosis. All the subjects had evidence of Helicobacter pylori infection. All received a treatment course of colloidal bismuth subcitrate four times a day and 250 mg metronidazole three times a day. There was impressive improvement in their symptoms, the halitosis disappearing along with eradication of the organism. We call the attention of physicians to the possible connection between halitosis, H. pylori infection, and familial occurrence. Further studies to confirm this surprising association are in order.

Antacids

Free fatty acids have nucleating effects in model biles.

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile

Effect of lipid infusion on bile composition and lithogenicity in patients without cholesterol gall stones.

A prospective study was performed to investigate the effect of short term lipid infusion on bile composition and its lithogenicity in humans. Thirty five patients shown to be free of cholesterol gall stones participated in the study. Starting 48 hours before surgery they were infused randomly with a lipid emulsion of either long chain triglycerides (LCT) or a mixture of medium and long chain triglycerides (MCT/LCT) (50%/50%) for six hours each 24 hours. A group of patients infused with a solution of 5% glucose in NaCl 0.9% served as a control. Bile samples were obtained by puncture of the gall bladder during operation. Both lipids caused an increase in biliary cholesterol and phospholipids but this effect was more pronounced and significant (p < 0.001) only with the MCT/LCT emulsion. The fatty acid composition of biliary phospholipids was not affected by either lipid infusion. The cholesterol saturation index increased significantly (p < 0.005) with the MCT/LCT emulsion and there was shortening in the nucleation time but this was not significant. There was no effect on the distribution of cholesterol between micelles and vesicles. This study shows that infusion of MCT/LCT lipid emulsion can cause lithogenic changes in bile composition in humans and may thus contribute to sludge formation and cholelithiasis during long term parenteral nutrition.

Bile

Streptococcus bovis endocarditis as a presenting manifestation of idiopathic ulcerative colitis.

Streptococcus bovis bacteraemia and endocarditis have been associated with several gastrointestinal diseases, mainly malignant or potentially malignant tumours, and less commonly non-malignant gastrointestinal disorders. We describe a 73 year old man in whom Streptococcus bovis endocarditis developed, and was the presenting manifestation of undiagnosed quiescent ulcerative colitis. Such an association has not been described previously.

Aged

Prostaglandin E2 in duodenal ulcer complications.

Prostaglandins are presumed to have cytoprotective properties and may play a role in the pathogenesis of duodenal ulcer and its complications. To evaluate this hypothesis, 35 patients with either duodenal ulcer bleeding (18 patients) or gastric outlet obstruction (17 patients) were investigated. Biopsies were taken from gastroduodenal tissues and secretions for prostaglandin E2 (PGE2) levels. These levels were compared to those taken from the same areas during a later endoscopy. A correlation was found between the severity of the clinical endoscopic findings and PGE2 levels. Increased levels of PGE2 were found in the quiescent phase and decreased levels found during the deteriorated phase. These differences of PGE2 levels were found to be of significant value (P less than 0.002). Furthermore, the patients in which the PGE2 levels were decreased at second endoscopy needed surgery. PGE2 may, thus, be a factor in duodenal ulcer pathogenesis and its complications, and be used as a prognostic marker and guide.

Acute Disease

The induction of lamellar stacking by cholesterol in lecithin-bile salt model systems and human bile studied by synchrotron X-radiation.

Small angle X-ray scattering (SAXS) with synchroton radiation was used to investigate interactions among lipid particles in lecithin-bile salt model systems and in native gallbladder biles. In model systems in the absence of cholesterol, isotropic, continuous spectra were found, indicating the absence of periodic structures. In the presence of excess cholesterol, interaction in the form of lamellar stacking was detected by the appearance of discrete diffraction peaks. In the supersaturated cholesterol region of the commonly accepted phase diagram [1], where cholesterol crystals were expected, we found lamellar stacking. The high proportion of cholesterol to bile salts seems to be the common denominator of these models. The lamellar stacking was also found in native unprocessed bile. This effect of cholesterol on lipid structure has not been previously described. Lamellar stacking may contribute to cholesterol solubilization. Its influence on the kinetics of cholesterol crystallization is presently unknown.

Bile

D-xylose absorption test. Urine or blood?

The D-xylose absorption test has been used during the last four decades for evaluation of malabsorption in the small intestine. However, some disagreement still exists about the recommended method of performing this test: the 1-hr blood test, the 5-hr urine test, or both. We evaluated the test by performing 125 combined blood and urine tests in 111 patients. Normal xylose absorption was recorded in both blood and urine in 71 tests (group A, 56.8%). Abnormal test results in both blood and urine were recorded in 29 patients (group B, 23.2%). Only one patient had a pathological blood value and normal xylose excretion in the urine. Twenty-four patients (group D, 19.2%) had normal 1-hr blood xylose (greater than 25 mg/100 ml) with abnormal 5-hr urine xylose (less than 4.5 g/5 hr). Fat and/or bile salt malabsorption were documented in 21 patients (87.5%) of this group using stool fat analysis and the [14C]cholylglycine breath test. These data suggest that in adults the 5-hr urine collection more accurately reflects intestinal absorption in comparison with the 1-hr blood value.

Adolescent

A controlled trial of beclomethasone versus betamethasone enemas in distal ulcerative colitis.

Steroid enemas are widely used in distal inflammatory bowel disease (IBD). They are partly absorbed and suppress adrenocortical function. Beclomethasone dipropionate (BD) is a topically active steroid that undergoes rapid first-pass inactivation in the liver and is practically devoid of systemic side effects. We treated 32 consecutive patients with active distal ulcerative colitis (40 attacks) with 0.5 mg BD and/or 5 mg betamethasone phosphate (BP) enemas for 28 days. Clinical, laboratory, sigmoidoscopic, and histologic data were recorded before, during, and after the trial. The clinical efficacy of both treatments was similar. Betamethasone was slightly more effective in relation to the histologic improvement and disappearance of blood from the stools. Clinical signs of steroid overdosage were noted in patients on BP but not in patients on BD. Mean fasting plasma cortisol at the end of the trial was 2.9 micrograms/dl in the BP group and 15.3 micrograms/dl in the BD group. The adrenocorticotropin test was markedly suppressed in the BP group but not in the BD group. The absence of systemic steroid side effects makes BD enemas a useful addition in the therapy of IBD. Its oral administration should also be considered.

Adult

Phospholipid lamellae are cholesterol carriers in human bile.

Cholesterol solubility and precipitation in bile are major factors in the pathogenesis of cholesterol gallstones. At present, mixed micelles and phospholipid vesicles are considered to be the only cholesterol carriers in bile. In this study we present evidence showing that phospholipid lamellae are major cholesterol carriers in human bile. Lamellae are a known aggregational form in pure phospholipid model systems. In the present study, lamellae were demonstrated by electron microscopy after negative staining and by small-angle X-ray diffraction in all human gallbladder bile samples examined. During diffraction experiments, cholesterol was found to crystallize from these lamellae. Cholesterol carriers in bile were separated by high-resolution chromatography and by prolonged ultracentrifugation. Lamellae were shown to solubilize most of the biliary cholesterol; vesicles solubilized a lesser amount; while micelles solubilized only a minor portion. Our data suggest that phospholipid aggregates are the main cholesterol carriers in bile. Bile salts may control the equilibrium between the various aggregational forms of cholesterol-carrying phospholipids.

Bile

Polyamines--potential nucleating factors in bile.

Lithogenicity of human bile is dependent not only on cholesterol saturation, but also on the presence of nucleating and antinucleating factors. Most of the research in this field is directed toward biliary proteins, particularly glycoproteins. In the present study we have shown that spermine, spermidine, cadaverine and putrescine have a nucleating effect in model bile as well as in native human bile. These findings are based on 183 mixing experiments using biles from 10 patients and model biles. The effect seems to be dose dependent at concentrations up to 10 mmol/l. It is not accompanied by a shift in cholesterol distribution between its vesicular and micellar carriers. It is at present uncertain whether these effects are pharmacologic or physiologic. These findings emphasize, however, the potential importance of non-protein compounds in the cholesterol nucleation process in bile.

Bile

Gel filtration and quasielastic light scattering studies of human bile.

Analyses of cholesterol carriers in the extremely variable biliary samples were performed by chromatography under standard conditions. Sephacryl columns were eluted with buffer containing 10 mmol/L sodium cholate, 150 mmol/L sodium chloride, 50 mmol/L Tris(hydroxymethyl)aminomethane-hydrochloride, pH 8.0, and 1.5 mmol/L ethylenediaminetetraacetate. Moderate changes in temperature, flow rate or sample size produced only minor differences in the results. Increments in bile salt concentration in the elution buffer caused progressive disappearance of vesicles and a rise in their cholesterol/phospholipid ratio. Using the standard chromatographic technique, analyses of the same bile gave reproducible results, and comparisons among various biles were possible. Quantitative light scattering measurements of bile showed that the amount of vesicular cholesterol in whole unprocessed bile was similar to that measured by Sephacryl chromatography. Analyses of human gallbladder biles using a high-resolution Sephacryl column showed four cholesterol-containing peaks: vesicles, lamellae, mixed micelles and an undefined carrier. This long chromatographic column separated the lamellar from the micellar peaks (which had merged on the short column). Phospholipid lamellae solubilized most of the biliary cholesterol. These findings were confirmed by ultracentrifugation of bile.

Bile

An evaluation of arbaprostil at multiple doses for the treatment of acute duodenal ulcer: a randomized double-blind placebo-controlled international trial.

Six hundred and thirty patients were enrolled in a randomized double-blind placebo-controlled trial evaluating two arbaprostil dosages (25 micrograms and 50 micrograms) qid for 4 wk for the treatment of acute duodenal ulcers. The healing rates in the placebo, 25-micrograms, and 50-micrograms treatment groups were 39%, 51%, and 60%, respectively. Smoking was found to adversely affect the healing rates in all the treatment groups. Pain severity was less with either arbaprostil treatment. The only side effect found was diarrhea: 10%, 14%, and 32% in the placebo, 25-micrograms, and 50-micrograms treatment groups, respectively. Severe diarrhea occurred in 1% of those patients who received the 50-micrograms dosage regimen, but in none of the other two groups. Arbaprostil at these two dosage levels, when given for 4 wk, appears to be a safe and efficacious agent for the treatment of acute duodenal ulcers.

Acute Disease

Biliary micellar cholesterol nucleates via the vesicular pathway.

Biliary cholesterol nucleates primarily from phospholipid vesicles. In this study, we investigated the mode of nucleation of micellar cholesterol. Ten biles (four human and six model) were examined. The vesicular and micellar fractions of each bile were separated by gel chromatography. The whole biles and their isolated carriers were incubated at 37 degrees C until nucleation time. In whole human biles, the proportion of total cholesterol in vesicles rose throughout the incubation (from zero time to nucleation time) from 15.5 +/- 8.6% to 28.0 +/- 12.5%, and in model biles from 46.8 +/- 22.4% to 75.5 +/- 8.2%. The vesicular isolated fraction remained unchanged throughout incubation. In isolated micelles devoid of vesicles at zero time, new vesicles formed during incubation, carrying increasing proportions of cholesterol. At nucleation time, these vesicles contained 11.0% of originally micellar cholesterol in human biles, and 41.2% in model biles. The new vesicles formed in whole bile and in the micellar fraction were chromatographically and chemically similar to the vesicles originally present in bile. These data suggest that micellar cholesterol nucleates via the neoformation of phospholipid vesicles, which seem to be the final common pathway for cholesterol nucleation in bile.

Bile

Prostaglandin E2 in pyloric stenosis.

Prostaglandins are presumed to have many cytoprotective properties that play a role in the pathogenesis of duodenal ulcer and its complications where decreased levels of prostaglandin E2 (PGE2) impair gastric motility, oppose ionic membrane influx, and enhance obstructive changes. These are just some of the mechanisms that may cause pyloric obstruction and may result from decreased PGE2 levels. To evaluate this hypothesis, 17 patients with duodenal ulcer complicated by pyloric stenosis were examined. Biopsy specimens were obtained from the duodenal bulb, ulcer margins, gastric antrum, fundus, and gastric secretions. Prostaglandin E2 levels were measured and compared with those taken from the same areas during a second endoscopy in a later quiescent or exacerbated phase. During the active phase of pyloric stenosis, decreased levels of PGE2 were found in the gastroduodenal tissues and secretions were compared with levels found during convalescence. These level differences were statistically significant. A correlation between the severity of the clinical and endoscopic findings and the PGE2 levels was found. A further decrease in PGE2 levels in the second endoscopy were indicative of the presence of scar tissue, representing an irreversible obstructive peptic disease.

Aged