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Biomedical subjects

T Gilat

Publications and source records attributed to T Gilat.

At least 55 records · Page 3Linked to original sources

Low incidence of significant dysplasia in a successful endoscopic surveillance program of patients with ulcerative colitis.

BACKGROUND/AIMS: Colorectal cancer associated with ulcerative colitis may be preceded by dysplastic changes potentially detectable by repeated endoscopic examinations. The aim of this study was to evaluate the incidence, course, and risk factors for dysplasia in a prospective endoscopic study. METHODS: One hundred fifty-four patients with ulcerative colitis for 7 or more years' duration were followed from 1976 to 1994 in an endoscopic surveillance program. RESULTS: Five patients had 10 adenomatous polyps managed by polypectomy. Indefinite dysplasia was found in 16 patients, and none showed progressive dysplasia on follow-up. Low-grade dysplasia was detected in 10 patients; 2 had and 2 progressed to high-grade dysplasia. High-grade dysplasia was found in 7 patients; 4 were concurrent with or just preceded cancer. All 4 cases of cancer were first detected by surveillance, and 3 were successfully treated. Significant risk factors for dysplasia (all grades) and cancer included the extent of disease (P < 0.01), older age at onset of colitis (P = 0.01), and the duration of disease (P < 0.05). The adjusted risk for cancer was significantly increased (P = 0.04). CONCLUSIONS: Indefinite dysplasia did not predict developing cancer. Low- or high-grade dysplasia was not frequent (8.5%) but was associated with progression to cancer. These can be detected and successfully treated by systematic endoscopic surveillance of patients with chronic (> or = 7 years), extensive (more than the rectosigmoid colon) ulcerative colitis.

Adenomatous Polyps↗

Behavior of cholesterol and spin-labeled cholestane in model bile systems studied by electron spin resonance and synchrotron x-ray.

The behavior of mixed bile salt micelles consisting of sodium taurocholate, egg phosphatidylcholine, and cholesterol has been studied by ESR spin labeling and synchrotron x-ray scattering. Consistent with published phase diagrams, pure and mixed bile salt micelles have a limited capacity to incorporate and, hence, solubilize cholesterol. Excess cholesterol crystallizes out, a process that is readily detected both by ESR spin labeling using 3-doxyl-5 alpha-cholestane as a probe for cholesterol and synchrotron x-ray scattering. Both methods yield entirely consistent results. The crystallization of cholesterol from mixed bile salt micelles is indicated by the appearance of a magnetically dilute powder spectrum that is readily detected by visual inspection of the ESR spectra. Both the absence of Heissenberg spin exchange and the observation of a magnetically dilute powder spectrum provide evidence for the spin label co-crystallizing with cholesterol. In mixed bile salt micelles containing egg phosphatidylcholine, the solubility of cholesterol is increased as detected by both methods. With increasing content of phosphatidylcholine and increasing mole ratio cholesterol/phosphatidylcholine, the anisotropy of motion of the spin probe increases. The spin label 3-doxyl-5 alpha-cholestane is a useful substitute for cholesterol provided that it is used in dilute mixtures with excess cholesterol: the cholesterol/spin label mole ratio in these mixtures should be greater than 100. Despite the structural similarity between the two compounds, there are still significant differences in their physico-chemical properties. These differences come to the fore when cholesterol is totally replaced by the spin-label: 3-doxyl-5a-cholestane is significantly less soluble in bile salt and mixed bile salt micelles than cholesterol and, in contrast with cholesterol, it interacts only very weakly, if at all,with phosphatidylcholine. The potential of the ESR method for detecting cholesterol crystal growth in human bile is discussed.

Bile Acids and Salts↗

High Helicobacter pylori numbers are associated with low eradication rate after triple therapy.

This study tested the influence of pretreatment bacterial density on the eradication rate of Helicobacter pylori with triple therapy. One hundred and thirty two patients with endoscopically confirmed H pylori positive, duodenal ulcer or antral gastritis were treated with triple therapy (colloidal bismuth/metronidazole/amoxicillin) for two weeks. Pretreatment urease activity was assessed by the 14C-urea breath test (UBT) in all patients. The mean (SD) pretreatment UBT concentration was similar in patients with duodenal ulcers (318.4 (175.0)) and patients with antral gastritis (288.9 (165.5)). Overall eradication of H pylori was achieved in 85 of 132 patients (64.4%), but was significantly different between patients with high, intermediate, or low pretreatment urease activity (37.5%, 69.5%, and 87.8% respectively). The mean post-treatment UBT value of patients in whom eradication failed was in direct correlation with the pretreatment UBT values. In conclusion, bacterial density, as assessed by urease activity, is an important factor in predicting H pylori eradication. It is suggested that the pretreatment UBT has the potential to identify patients who require modification of the standard therapeutic regimen.

Amoxicillin↗

Post-transfusion etiology and non-cirrhotic histology improve the remission rate of chronic hepatitis C during interferon treatment.

During a 29 month period, 46 patients with chronic hepatitis C virus (HCV) received recombinant human interferon alpha-2a for 6 months and were followed for another 6 months. The dose of interferon was three million units thrice weekly and was increased to six million units if amino transferase levels failed to return to normal after 2 months of therapy. At the end of the treatment 19 patients had a complete response, 6 had a near complete response, 2 patients had breakthrough during treatment, and the remaining 19 did not respond at all. Six months after treatment only 10 of the 19 responders remained in remission. Post-transfusion disease was associated with a significantly higher remission rate than sporadic disease (9/22 vs. 1/24, P < 0.001), as was also found in non-cirrhotic compared to cirrhotic patients (9/27 vs. 1/19, P < 0.001). Age, sex, duration of disease, serum aminotransferase, albumin, bilirubin, alkaline phosphatase, or Child's classification did not correlate with treatment response. Severe side effects necessitating cessation of treatment occurred in six patients, four of whom had major autoimmune phenomena. We conclude that careful selection of HCV patients with favorable response characteristics (post-transfusion etiology and non-cirrhotic liver) and without autoimmune manifestations can improve the remission rate and decrease the complication rate during interferon treatment.

Adult↗

[Antimicrobial sensitivity and treatment of Helicobacter pylori infections].

Helicobacter pylori (HP) is considered the etiological agent of chronic active gastritis and suspicion is strong that it plays an important role in duodenal ulcer. Recently, several clinical studies reported that eradication of HP markedly reduces the frequency of ulcer relapse. Triple-drug treatment, including a bismuth salt and 2 antibiotics (usually metronidazole with either amoxycillin or tetracycline) is considered the treatment of choice. It has been shown that the most important factor for predicting success of treatment is the sensitivity of HP to metronidazole, which varies considerably. In the present study we evaluated antimicrobial susceptibility of 18 HP clinical isolates, as well as effectiveness of triple therapy for eradicating HP infections in 65 patients. In vitro, HP was highly sensitive to amoxycillin, erythromycin and tetracycline (100%), and also to metronidazole and tinidazole (94%). Sensitivity to chloramphenicol was low (50%). In our clinical study, the overall eradication rate was 66%; it was higher among women (80%) than men (54%), probably due to better compliance. It is concluded that HP strains in Israel are highly sensitive to metronidazole and that triple therapy is effective, providing compliance is good.

Amoxicillin↗

Effect of dietary phospholipids and their constituents on bile composition in rats and hamsters.

The formation of cholesterol gallstones is a result of an interaction between bile lipid concentration, composition and other factors. The solubilization of cholesterol in bile is affected by the nature of the fatty acids and head groups of biliary phospholipids. In this study we tried to modulate the composition of biliary lipids in the rat and hamster by means of dietary supplementation of whole phospholipids or their constituents (at 3% to 5% of food weight). A striking effect of ethanolamine feeding in rats and hamsters was demonstrated: Biliary cholesterol concentration and cholesterol saturation index were significantly lower (p < 0.03). In rats, bile acid concentration was increased, contributing to decreased bile lithogenicity. Ethanolamine also increased biliary phospholipid output. Other test substances had less marked effects. The addition of lecithin to rat diet significantly increased phospholipid concentration (p < 0.05) compared with controls. Cholesterol and bile acid concentrations were reduced in palmitic acid-fed hamsters (NS). Choline supplementation insignificantly increased the cholesterol saturation index in hamsters. Despite the clear effect of ethanolamine on biliary lipid composition, no change could be demonstrated in the proportion of phosphatidylethanolamine in bile. It is postulated that ethanolamine was methylated in the liver to choline. Our data demonstrate that biliary lipid composition can be modulated by dietary phospholipids or their components.

Animals↗

Increased serum iron and iron saturation without liver iron accumulation distinguish chronic hepatitis C from other chronic liver diseases.

One hundred twenty-three patients with chronic liver diseases of various etiologies were evaluated for their iron status. The patients were divided into four distinct groups: chronic hepatitis C (63), chronic hepatitis B (14), B + C (3) and nonviral chronic liver diseases (43). In 107 patients (87%) the chronic liver disease was confirmed by biopsy. Mean serum iron (+/- SD) levels in the above four groups were: 166 +/- 62, 103 +/- 52, 142 +/- 48, and 115 micrograms/dl; iron-binding capacity was 346 +/- 80, 325 +/- 72, 297 +/- 27, and 374 +/- 75 micrograms/dl, and iron saturation 50 +/- 18, 32 +/- 16, 48 +/- 16, and 28 +/- 10%, respectively. Serum ferritin, increased in all four groups, was highest in HCV; however, no evidence of hepatic iron accumulation could be found in any of the patients. There were no significant differences in liver function parameters measured in the four groups. We conclude that serum iron, iron saturation, and ferritin are increased in patients with hepatitis C in comparison to hepatitis B or other nonviral, nonhemochromatotic liver diseases. The increased iron status in hepatitis C patients is not manifested by increased liver iron. Awareness of these distinct features of chronic hepatitis C is essential in the diagnosis and treatment of chronic liver diseases.

Biopsy↗

The distribution of the biliary-anionic polypeptide fraction between cholesterol carriers in bile and its effect on nucleation.

The small (7 kD) biliary phospholipid and calcium binding polypeptide (anionic polypeptide fraction/calcium binding protein) has been found in higher concentrations in the bile of patients with pigment stones than in controls. In different model systems it was variously found to promote or retard cholesteral crystalization. In the present study we investigated its distribution between cholesterol carriers in bile and its effect on cholesterol crystalization in native and model biles. On gel chromatography anionic polypeptide fraction/calcium binding protein was found predominantly in three areas: in the vesicular fraction, in the non-vesicular lipid fraction and in another fraction unassociated with biliary lipids. It was much more concentrated in the vesicular than in the non-vesicular fraction, the mean anionic polypeptide fraction/phospholipid molar ratio being 219 +/- 181 vs. 30.4 +/- 16, respectively. Anionic polypeptide fraction/calcium binding protein was added at three dose levels, 0.14, 0.28, 0.42 mg/ml (representing approximately 18%-55% of the physiologic biliary concentration), to 19 human and five model biles. This did not produce any significant changes in the nucleation time. The addition of anionic polypeptide fraction/calcium binding protein at a dose level of 0.42 mg/ml to 13 different human biles did not induce changes in the distribution of cholesterol among its carriers. The present experiments do not support a role for anionic polypeptide fraction/calcium binding protein in the process of cholesterol nucleation in bile. Qualitative changes in the protein molecule, as demonstrated in other human secretions, cannot be excluded.

Apoproteins↗

Ileitis after colectomy for ulcerative colitis or carcinoma.

An ileitis developing years or months after ileostomy was recognised and described many years ago but has rarely been mentioned since. We describe nine patients with a non-specific preanastomotic ileitis that developed years after colectomy in patients operated on for ulcerative colitis or carcinoma. The disease developed after various types of reconstruction: ileorectal, ileoanal, with or without pouch. The diseased ileum showed inflammation, erosions, ulcerations, and sometimes strictures. The disease course ranged from asymptomatic to severe pain and diarrhoea. No specific cause could be shown. Granulomas, infectious agents or ischaemic changes were not found. The anastomosis was always patent. Three patients have had numerous episodes of intestinal obstruction presumably because of adhesions. Seven of nine patients were female. The response to steroids, 5-aminosalicylic acid preparations, and methotrexate was poor, three patients responded well to azathioprine. The condition is not rare and the cause remains unknown.

Adult↗

Morphological transformation of Helicobacter pylori during prolonged incubation: association with decreased acid resistance.

The survival of clinical isolates of H pylori at two cultural ages (two and four days) at pH 2, in the presence of different buffers, with and without urea, was investigated. It was found that the morphological changes which occur with longer incubation of H pylori have an inverse correlation with its resistance to an acidic environment. The finding that the addition of urea almost reversed this phenomenon and prolonged survival of the cultures emphasises the role of urea in the survival of H pylori in acidic environments.

Acids↗

An eight year experience with upper gastrointestinal bleeding: diagnosis, treatment and prognosis.

Bleeding from the upper gastrointestinal tract is one of the most common medical emergencies. Admission of patients to a specialized care unit may reduce morbidity and mortality. All patients admitted to the Tel Aviv Medical Center, between January 1, 1983 and December 31, 1990 with acute upper gastrointestinal bleeding, or those who bled while in the hospital, were seen and assessed by a senior member of the gastrointestinal service. Endoscopy was performed within 24 hr of admission. A total of 1110 endoscopies were performed. Duodenal ulcer was the main source of bleeding (40.0%). Injection of a vasoconstrictor was used for very small blood vessels. Thermal methods were used for small or medium sized vessels, or for oozing from a margin ulcer; both with equal rates of success. 153 (13.8%) surgical procedures were performed. Three (0.37) patients had endoscopic cardiovascular complications; one of them died. The in-hospital mortality was 5.9%. Increasing age, other medical problems, rebleeding and an admission hemoglobin of 8 g/dL or less, were associated with increased mortality. Our policy of early clinical and endoscopic assessment, and rapid surgical intervention in those at high risk, markedly improved survival.

Adolescent↗

Achalasia in central Israel, 1973-83: clinical aspects.

In the framework of an epidemiologic study we collected data on all the 162 patients with achalasia in central Israel. The mean (+/- SD) follow-up was 9.9 +/- 8.7 years (range 1-52). At the last, as compared to the initial examination, the clinical condition of the patients had improved: 38% were without dysphagia as compared to 0% initially, 67% did not vomit and 92% did not complain of aspiration as compared to 17% and 68% initially, and 67% did not complain of chest pain as against 36% initially. In contrast, X-ray examinations, endoscopy as well as manometry did not show major changes. Esophageal retention of a semisolid radiolabeled meal 10 min after ingestion was 46 +/- 25% initially and 34 +/- 26% at last examination (NS). Medical therapy was given to 99 patients and a beneficial response was initially noted in 65% of them. About 88.7% had a beneficial response to surgery and 82.7% to pneumatic dilatations which were associated with a 7.3% perforation rate. Overall the clinical course of this unselected, regional group of patients was better than expected.

Adolescent↗

Seasonal variation in the frequency of Helicobacter pylori infection: a possible cause of the seasonal occurrence of peptic ulcer disease.

OBJECTIVES: The seasonal variation of duodenal ulcer disease and its complications have been repeatedly demonstrated in Israel by several independent studies. The aim of this study was to determine possible seasonal variations in the occurrence of H. pylori infection among dyspeptic patients in Israel. METHODS: All 14C-urea breath tests performed in dyspeptic patients at the gastroenterology department in the Tel Aviv Medical Center from January 1991 to December 1992 were reviewed. The monthly variation in the proportion of patients with H. pylori infection was determined, and compared with that of an unrelated 14C-cholyl-glycine breath test. RESULTS: Altogether, 702 patients were examined, and 371 (52.8%) of them were found to be infected with H. pylori. During summer months (July-September), a significant decrease in the percentage of patients infected with H. pylori was found, compared with winter months (December-January, 42.3% vs. 60.9%, p < 0.007). No seasonal variation was found in the results of 14C-cholyl-glycine test. The fluctuations in H. pylori infection were highly correlated with the seasonal occurrence of peptic ulcer disease in Israel. CONCLUSIONS: The frequency of H. pylori infection in dyspeptic patients in Israel is significantly increased during the winter months and decreased in the summer. This seasonal variation is identical to that found in duodenal ulcer disease. Thus, the seasonal variation of peptic ulcer disease could be explained by H. pylori infection, as seen in other communicable infectious diseases.

Breath Tests↗

Epidemiology of achalasia in central Israel. Rarity of esophageal cancer.

The epidemiology of achalasia was studied in a predominantly urban, Jewish population of approximately 1.3 million, in central Israel, during the years 1973-1983. One hundred sixty-two proven cases were collected, representing all known patients with achalasia in the study area. There were no gender differences. The majority of cases were diagnosed within two years of onset of symptoms, although the median delay in diagnosis was 4.4 +/- 5.3 years. The disease was rare in the first two decades of life. The prevalence (in 1983) in the first two decades was 0.7/10(5) rising to 36.2/10(5) above age 70. The mean annual incidence in the years 1973-1978 was 0.8/10(5). It rose slightly to a mean annual incidence of 1.1/10(5) in the years 1979-1983. The prevalence of the disease in 1973 and 1983 was 7.9/10(5) and 12.6/10(5), respectively. The age-adjusted prevalence in 1973 was higher in Asian and African born Jews as compared to those born in Europe, America, or Israel. This difference disappeared by the year 1983. No case of cancer of the esophagus was found among our patients. This may be due to the nonselected, regional nature of our series or to the effects of earlier therapy of achalasia in recent decades.

Adult↗

Success of estrogen-progesterone therapy in long-standing bleeding gastrointestinal angiodysplasia. Report of a case.

Gastrointestinal angiodysplasia is a common cause of occult bleeding. Surgical and endoscopic treatments are often ineffective. Recently, estrogen-progesterone therapy proved to be effective in these patients. We describe herein an 84-year-old man who presented with prolonged gastrointestinal bleeding, in whom treatment with estrogen-progesterone stopped the bleeding. We suggest that hormonal therapy should be considered in cases of prolonged obscure gastrointestinal bleeding thought to be due to angiodysplasia. This therapy should be instituted intermittently for a prolonged period. The role of progesterone, especially in men, should be reconsidered.

Aged↗

Effect of inoculum size on antimicrobial susceptibility of Helicobacter pylori.

An agar dilution assay was used to assess the effect of inoculum size and culture period on the susceptibility of 15 clinical isolates of Helicobacter pylori to ampicillin, erythromycin, tetracycline, chloramphenicol, metronidazole and tinidazole. The mean MIC of the isolates increased 2.2- to 21.2-fold as the inoculum size progressed from 10(3) to 10(7) cfu/spot. Identical results were noted when isolates were maintained for two or four days prior to testing. Inoculum size should be carefully controlled when assessing the in vitro susceptibility of Helicobacter pylori.

Helicobacter pylori↗

Determination of free polyamines in human bile by high-performance liquid chromatography.

1. Polyamines are widely distributed in the body and may have cholesterol-nucleating activity in model bile and human bile. There are only partial and scant data available on the type of polyamines in human bile. 2. In this study methods for extraction of free polyamines, benzoylation and an h.p.l.c.-based method for the quantitative determination of putrescine, cadaverine, spermidine and spermine in bile are described. The h.p.l.c. methodology was validated and compared with separation on t.l.c. after dansylation. 3. The polyamine content of 11 gallbladder bile samples and 11 T-tube bile samples was analysed, all from patients with gallstones. Polyamines were found in three out of 11 gallbladder bile samples and eight out of 11 T-tube bile samples. Putrescine levels were 0.5-287 mumol/l and cadaverine levels were 2.4-645.4 mumol/l; these were considerably higher than spermine and spermidine levels. 4. As many of these gallstones bile samples were devoid of polyamines, it is questionable whether polyamines play an important role in cholesterol nucleation in human bile.

Bile↗

Bile and plasma lipid composition in non-obese normolipidemic subjects with and without cholesterol gallstones.

A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.

Bile↗