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T Gilat

Publications and source records attributed to T Gilat.

At least 37 records · Page 2Linked to original sources
PubMed1997

Monitoring cholesterol crystallization from lithogenic model bile by time-lapse density gradient ultracentrifugation.

BACKGROUND/AIMS: Cholesterol crystallization in a dilute, bile salt-rich model bile is a multiphase process in which early filamentous crystals gradually transform to classical cholesterol monohydrate plates. The pertinence of similar transformations in more complex model systems or native bile is, however, unclear. The aim of the present study was to characterize and monitor cholesterol crystallization in a model bile of physiological relevance. METHODS: A supersaturated model bile was prepared with a lipid composition (18 mM cholesterol, 37 mM lecithin, 120 mM taurocholate) that was derived from analyzing 10 gallbladder biles from cholesterol gallstone patients. Cholesterol crystallization was followed by light and electron microscopy, and sequential density gradient analysis of cholesterol-containing precipitates. RESULTS: During cholesterol crystallization a reproducible sequence of events was recorded. First (T<18 h), cholesterol-rich vesicular and multilamellar structures (density 1.005-1.015 g/ml) were observed. Later, (T>60 h) filamentous, helical, tubular (density 1.015-1.04 g/ml) and plate-like (density 1.04-1.06 g/ml) cholesterol crystals appeared. The concentration of crystals increased gradually, while bilayer structures became desaturated with cholesterol and disappeared, and early crystal forms were replaced by plates. Eventually (T>25 days) only classical plate-like cholesterol monohydrate crystals were present. Exposure of cholesterol-containing precipitates to micellar (100 mM) deoxycholate dissolved the bilayer structures but not the crystals. CONCLUSIONS: These data demonstrate that cholesterol crystallization in a physiologically relevant model bile is a multiphase process consisting of a sequence of transitions from vesicular and multilamellar structures to early crystal forms and to classical plate-like cholesterol monohydrate crystals. These transitions are associated with increasing density and decreasing phospholipid content of cholesterol precipitates. We suggest that time-lapse density gradient ultracentrifugation is a useful method for investigating and quantitating the process of cholesterol crystallization and factors that influence this process in bile.

Animals↗
PubMed1997

The absorption of low-dose methotrexate in patients with inflammatory bowel disease.

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.

Adult↗
PubMed1997

Pre-illness dietary factors in inflammatory bowel disease.

BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.

Adult↗
PubMed1997

A new method for the rapid measurement of cholesterol crystallization in model biles using a spectrophotometric microplate reader.

Measurements of the cholesterol crystal observation time, and particularly the crystal growth rate in model biles, are important in biliary pathophysiology. The aim of this study was to develop a semi-automated method permitting multiple, simultaneous, and precise measurements of the crystal growth rate in model biles. Incubated model biles were mixed with a high concentration of NaTDC to solubilize non-crystalline turbidity and spectrophotometric measurements were performed. In parallel, samples were observed by light microscopy. The absorbance correlated linearly with the crystal mass and permitted quantitation of the crystal growth rate. Polarized light microscopy was more sensitive than spectrophotometry for determining the initial crystal observation time, while spectrophotometry was more precise and quantitative for measuring the crystal growth rate.

Bile Acids and Salts↗
PubMed1997

Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND: At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD). AIM: To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD. PATIENTS: Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied. METHODS: Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated. RESULTS: Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD.

Abdominal Pain↗
PubMed1996

Lithogenicity of human bile is reduced by freezing and thawing.

We examined the effects of freezing and thawing upon the nucleation time and the distribution of cholesterol between micelles and vesicles in 9 human gallbladder and 7 hepatic biles. The nucleation time was significantly longer after freezing when compared to fresh samples (22.4 +/- 2.6 vs. 7.4 +/- 1.9 days, respectively). Concomitantly, a substantial shift of cholesterol from vesicles to micelles was noted, with the proportion of vesicular cholesterol decreasing from 26.5% +/- 6.0% in fresh biles to 8.6% +/- 2.3% after freezing. These effects were observed in all types of human biles, regardless of origin, cholesterol saturation or initial presence of cholesterol crystals, and were most notable after the first week of freezing. The decrease in vesicular cholesterol in all biles and the increase in nucleation time of gallbladder biles correlated with the time the samples had been in a frozen state. It is concluded that the lithogenic properties of human bile are not maintained during storage at -20 degrees C. Freezing results in a shift of cholesterol from vesicles to micelles and reduces the tendency of cholesterol to crystallize from bile samples.

Bile↗
PubMed1996

Increased leukocyte adhesiveness/aggregation in patients with inflammatory bowel disease during remission. Further evidence for subclinical inflammation.

PURPOSE: We have used a novel leukocyte adhesiveness/aggregation test (LAAT) to show that many patients with inflammatory bowel disease (IBD) in clinical remission have a subclinical low grade inflammation. METHODS: Included in the study are 500 controls, 96 patients with IBD in remission, and 106 patients in relapse. RESULTS: The percent of aggregated white blood cells detected in the peripheral blood was 5.9 +/- 3.9, 9.1 +/- 5.9, and 18.8 +/- 9.4, respectively. The difference between each group and any other was significant at P < 0.0001. Similar results were obtained when other acute phase reactants like the erythrocyte sedimentation rate, white blood cell count, differential count, and C-reactive protein level were examined. However, in a linear regression analysis, LAAT was the only significant (P < 0.0006) variable that could classify correctly each subject to the appropriate category of control and IBD in remission or relapse. CONCLUSIONS: Identification of patients with IBD in clinical remission who have ongoing inflammation may be of clinical-therapeutic relevance. The LAAT is a simple, rapid, and convenient test. The present study indicates that it is also very sensitive.

Adolescent↗
PubMed1996

Esophageal smooth muscle dysfunction in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder with late-onset progressive myopathy affecting mainly head and neck striated muscles. It is more common in certain ethnic communities. Dysphagia was usually attributed to the malfunction of striated pharyngeal muscles. We studied a group of Bukharan immigrants affected by this disorder (N = 13). Esophageal studies, including endoscopy, manometry, and scintigraphic emptying were performed. Very low pharyngeal pressures were measured. Upper esophageal pressures (UEP) were in the normal range in eight patients, and above normal in three patients. Four also had low lower esophageal sphincter pressure. Esophageal body peristaltic activity was grossly impaired in all patients: mainly nonpropulsive, simultaneous, retrograde, and failed activity was recorded. Marked retention of isotopic material was demonstrated in all patients studied, usually in the middle and lower parts of the body, ranging from 17 to 100% retention. The dysphagia in OPMD is due not only to dysfunction of pharyngeal and upper esophageal striated muscle, but also has a significant smooth muscle component.

Adult↗
PubMed1996

The effects of dietary phospholipids enriched with phosphatidylethanolamine on bile and red cell membrane lipids in humans.

The role of phospholipids in biliary cholesterol solubilization and crystallization has only recently begun to be appreciated. Phospholipid vesicles are believed to be the metastable carrier from which cholesterol nucleates. Cholesterol crystallization is influenced by the phospholipid species in bile. Feeding rats and hamsters with diets enriched in phospholipids or their precursors, especially ethanolamine, resulted in reduced cholesterol saturation of bile. Although whole phospholipids are normal dietary constituents, the effects and safety of phospholipid components have not been tested in humans. In the present study, we have evaluated the effects of a dietary phospholipid mixture, enriched with phosphatidylethanolamine, on human bile and red blood cell membrane lipid composition. Five ambulatory volunteers having a chronic indwelling T-tube, with an intact enterohepatic circulation, were investigated. Thirty-six grams of phospholipids (54% phosphatidylethanolamine, 54% linoleyl acyl chains) were added to their daily diet for fourteen days. Biliary nucleation time, cholesterol carriers, as well as plasma, red blood cell membrane, and bile lipid compositions, were monitored. Following phospholipid supplementation, the proportion of linoleyl chains (18:2) in biliary phospholipids increased significantly from 31.1 +/- 1.2 to 37.7 +/- 5.3%, while that of oleyl chains (18:1) decreased from 11.4 +/- 1.6 to 9.6 +/- 1.1%. These changes were accompanied by an increase of linoleate and its metabolite, arachidonate, in red cell membranes. Phospholipid feeding did not cause any side effects, and no significant changes in biliary nucleation time, cholesterol, phospholipid, or bile salt concentrations, or in the distribution of cholesterol within micelles or vesicles. We conclude that phospholipid feeding is safe, and can be effective as a vehicle for lecithin fatty acyl chain modulation of bile and lipid membranes. These findings may provide a basis for a controlled modulation of biliary phospholipids to increase cholesterol solubility in bile.

Adult↗
PubMed1996

One week triple therapy with omeprazole, clarithromycin and tinidazole for Helicobacter pylori: differing efficacy in previously treated and untreated patients.

BACKGROUND: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) has been found to be highly effective against Helicobacter pylori infection. However, its efficacy as a second line regimen for patients who failed metronidazole-based triple therapy has not been evaluated. AIM: The aim of this study was to evaluate the efficacy of low-dose, short-term OCT therapy in an Israeli population, and to compare results obtained in previously treated and untreated patients. METHODS: Patients with duodenal or gastric ulcers and chronic antral gastritis with H. pylori infection as assessed by rapid urease test and/or 14C urea breath test (14C-UBT), were studied. All patients received omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days. Eradication was assessed by 14C-UBT 4 weeks after treatment. RESULTS: One hundred and fourty-four patients (M/F = 81/63) were enrolled (mean age 48.1 years, range 12-78). Eradication of H. pylori was significantly different between patients who were initially treated with this regimen (90/94, 96%) and patients who had previously failed to eradicate H. pylori with standard triple therapy (27/50, 54%). Moreover, the eradication rate was significantly decreased in patients with more than one previous failure (9/22, 41%) compared to that in patients with only one failure (18/29, 62%). No other differences such as age, gastric pathology, ethnic origin, smoking habits, or pre-treatment urease activity were found to influence the eradication rate. CONCLUSIONS: One-week low-dose triple therapy with OCT is highly effective as an initial therapy in eradicating H. pylori infection. The efficacy is significantly lower when given as a second line treatment in patients who have previously failed to eradicate H. pylori with bismuth-based standard triple therapy.

Adolescent↗
PubMed1996

Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND & AIMS: Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis. The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a randomized, double-blind multicenter trial. METHODS: Patients with active ulcerative colitis who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study. Methotrexate (12.5 mg) or placebo was added to their treatment once weekly for 9 months. RESULTS: Sixty-seven patients were included (methotrexate, 30 patients, placebo, 37 patients). The proportion of patients entering first remission (methotrexate, 46.7%; placebo, 48.6%), the time to reach first remission (methotrexate, 4.1 +/- 1.9 months; placebo, 3.4 +/- 1.7 months), as well as the proportions of patients having a relapse after first remission (methotrexate, 64.3%; placebo, 44.4%) were not significantly different between the two groups. The mean Mayo Clinic score, the mean monthly steroid dose, and the proportion of abnormal laboratory results during the study were also similar. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis.

Administration, Oral↗
PubMed1996

Characteristics of gallbladder bile of infants and children.

In the past, biliary lipids of infants and children were studied in duodenal aspirates. This study was performed on original bile aspirated from the gallbladder. The analysis of lipids in bile demonstrated a significantly lower total lipid content in the bile of infants than in children (3.3 g/dl vs. 9.1 g/dl). The most prominent difference was demonstrated in the bile salt concentration (43.2 mM vs. 126.7 mM) and thereafter in the phospholipid content. Infants had a shorter nucleation time and a higher cholesterol saturation index than did children. These results may explain the increased tendency of infants to produce sludge and gallstones during total parenteral nutrition.

Bile↗
PubMed1996

Increased leukocyte adhesiveness/aggregation is the single best biochemical indicator of disease activity in adolescent patients with inflammatory bowel disease.

We determined the relative utility of inflammatory markers in evaluating disease activity in adolescent patients with inflammatory bowel disease (IBD). Sixty-one adolescent patients and 50 age and sex matched volunteers who served as controls were evaluated prospectively. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBCC), and the leukocyte adhesiveness/aggregation (LAA) test were determined in each patient. There were 28 subjects in remission and 33 in relapse. Their percentage of aggregated white blood cells in the peripheral blood was 7 +/- 5 and 16 +/- 8, respectively, when compared with the control group (5 +/- 3) (p < 0.0001). Moreover, the LAA test was the only one which could effectively classify patients with IBD into their correct diagnostic categories of remission, mild-moderate, or moderate-severe disease activity. The LAA test is superior to other acute phase reactants used in daily practice to detect the presence of inflammation as well as for the assessment of its severity in adolescent patients with IBD. In addition, our findings may have biological relevance to the disease process and its potential manipulation by anti-adhesive agents.

Adolescent↗
PubMed1995

Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection.

To date, there are no firm clinical, demographic, biochemical, serologic, or histologic features predicting which patients with chronic hepatitis C are more likely to respond to therapy with interferon-alpha. Serum iron, total iron-binding capacity, transferrin saturation, and ferritin were measured in the fasting state. The amount of stainable iron in liver biopsy specimens was evaluated histochemically as well. All patients received subcutaneous recombinant human IFN-alpha 2a three million units thrice weekly by self-administration. Eleven of 13 (84%) responders had low to normal serum iron levels as compared to one of 26 (4%) nonresponders (P < 0.001). The serum transferrin was similar in both groups, but iron saturation was significantly lower in responders (30 +/- 10%) than in nonresponders (53 +/- 12%) (P< 0.001). Serum ferritin and hepatic iron content were higher in nonresponders (NS). It is suggested that increased serum iron and transferrin saturation blunt the action of interferon, as they have opposite effects on the immune system. Iron overload can thus lead to a poor response to interferon. It remains to be seen whether reducing iron overload will improve the response to interferon therapy.

Chronic Disease↗
PubMed1995

Lack of association between smoking and inflammatory bowel disease in Jewish patients in Israel.

BACKGROUND/AIMS: An excess of smokers in patients with Crohn's disease (CD) and a paucity of smokers in patients with ulcerative colitis (UC) were reported in many studies. The aim of this study was to examine the association between smoking and inflammatory bowel disease (IBD) in Israel. METHODS: Two independent studies were performed. Patients with recent IBD in comparison with matched population and outpatient controls and patients with chronic UC and CD were studied. Altogether, 475 subjects were investigated. RESULTS: In both studies, the presence of current smokers was lower in CD (9% and 18%) than in UC (24% and 26%). The proportions of nonsmokers in both studies were similar (UC, 61% and 65%; CD, 67% and 70%) and comparable to those found in their two control groups (57% and 61%; 63% and 68%, respectively) and to the general population of Israel. All differences in smoking habits between patient groups and their controls were not statistically significant, except for the paucity of current smokers in the small group of patients with newly diagnosed CD (P < 0.05). A matched analysis produced similar results. CONCLUSIONS: The expected associations between smoking and IBD could not be confirmed. Two hypotheses are considered: (1) the association between smoking and IBD may not be universal, and (2) our findings may be related to the higher genetic predisposition to IBD in Jewish people.

Adult↗