Tuvia Gilat

Childhood Factors in Ulcerative Colitis and Crohn's Disease: An International Cooperative Study

This international case control study was conducted in 14 centers in 9 countries to investigate factors in childhood which may have a bearing on the etiology or pathogenesis of ulcerative colitis (UC) and Crohns disease (CD). 197 patients with UC and 302 with CD (499 with inflammatory bowel disease (IBD] whose disease started before age 20 years and whose age at time of study was less than 25 years were investigated, with two age- and sex-matched controls for each patient. All subjects were studied with uniform questionnaires. Eczema was found significantly more frequently in patients with CD (p less than 0.005) and in their fathers (p less than 0.025), mothers (p less than 0.002), and siblings (p less than 0.01) as compared with their respective controls. IBD was significantly more frequent in parents, siblings, cousins, grandparents, and uncles of patients than in their respective controls. The fathers of patients with UC had significantly more major gastrointestinal and cardiovascular diseases at the time of the patients birth than the fathers of controls. In North America mothers of patients with UC and CD took vitamin, mineral, and iron preparations during pregnancy significantly less frequently than mothers of controls. Patients with CD and UC consumed a lower residue diet than controls. Recurrent respiratory infections were more frequent in patients with UC and CD (p less than 0.001); it is uncertain whether this preceded disease. Hospitalization for respiratory diseases was more frequent in patients than controls, and the use of antibiotics more frequent in patients with CD. Smallpox vaccination was less frequent (p less than 0.05) in patients with CD, and chickenpox infection was less common in patients with UC (p less than 0.01). No significant differences were found between patients and controls in relation to various human and non-human contacts during childhood. Number of siblings, being an only child, and birth order did not differ markedly between patients and controls, and we could not confirm the sheltered child hypothesis in IBD. The parents of controls were slightly better educated and their social class tended to be higher than those of parents of patients. There were significant associations between some of the main factors investigated in this study. No significant differences were found between patients and controls in the frequency of breast feeding, cereal consumption, sugar added to milk in infancy, gastroenteritis in childhood, major stressful life events, and many other factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Intestinal Cancer in Patients with Crohn's Disease: A Population Study in Central Israel

A population study of Crohns disease (CD) during the years 1970-1980 was performed in a defined area in central Israel with 1,400,000 inhabitants. Three hundred and sixty-five patients with definite CD were identified, and a complete follow-up was obtained with particular attention to intestinal cancer. The mean follow-up time was 9.95 years (range, 1-49 years). Forty-four per cent of the patients were operated on, but only a few had total colectomy or bypass operations. Only one patient developed colorectal cancer after 7 years of disease. The observed to expected ratio for this cancer was 1.14 at 10 years of disease and 0.73 at 20 years of disease. The incidence of colorectal cancer was not significantly different from the expected in the population. None of the patients developed small-bowel cancer. At least five patients had extraintestinal malignancies. A review of the literature showed conflicting results with regard to cancer risk in CD. The risk was not significantly increased in the two existing population studies, including the present one.

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 µg/dl; iron-binding capacity was 346 ± 80, 325 ± 72, 297 ± 27, and 374 ± 75 µg/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.

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

BACKGROUND/AIMSnColorectal 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.nnnMETHODSnOne hundred fifty-four patients with ulcerative colitis for 7 or more years duration were followed from 1976 to 1994 in an endoscopic surveillance program.nnnRESULTSnFive 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).nnnCONCLUSIONSnIndefinite 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.

An Increased Familial Frequency of Gallstones

Despite the very high prevalence of gallstone disease, studies of familial factors are very few, and asymptomatic family members were not studied. We studied, in a prospective manner, the frequency of gallstones in 171 first-degree relatives of patients with proven gallstones compared with 200 matched controls. All subjects were studied by oral cholecystography, and their height, weight, blood glucose, cholesterol, and other parameters were measured. Gallstones were found in 20.5% of the family group and in 9.0% of the control group. Gallstones were found in 22.8% of the female and 16.7% of the male family members as opposed to 10.3% of the female and 8.0% of the male controls. All these differences were statistically significant. Known risk factors, such as Ashkenazi community group, higher age, and overweight, were more frequent in the control group, as were blood glucose and cholesterol. These findings strengthen the validity of the twofold higher frequency of gallstones found in the family group and are likely to be due to genetic factors. A formal genetic family study of gallstone disease is now indicated, using the ultrasonic method.

The causes of hypoxemia in elderly patients during endoscopy.

Changes in arterial gas tensions were determined in 114 patients undergoing elective gastrointestinal endoscopic examinations with standard or pediatric gastroscopes or colonoscopes. All patients were premedicated intravenously with 0.5 mg of atropine and 10 mg of diazepam. In addition, two thirds received a narcotic, either 50 mg of meperidine or 0.05 mg of the short acting drug fentanyl. The choice of instrument or premedication was usually sequential. There was significant depression of the arterial oxygen tension (Pao2), of 17.4%, immediately following premedication that included a narcotic but not with diazepam alone. Significant reduction of the Pao2 persisted during upper endoscopy if a standard gastroscope was used and meperidine or fentanyl was included in the premedication. If a narrow diameter gastroscope was employed, only meperidine was associated with persistent depression of the Pao2. To minimize hypoxia in elderly patients during upper endoscopy, no narcotic or only a short acting one should be included in their premedication, and a narrow diameter instrument should be used for the examination.

Factors affecting methane production in humans: gastrointestinal diseases and alterations of colonic flora

Breath methane was studied in 394 subjects. Among 152 controls, 50.0% produced methane-42.1% of males and 57.9% of females. One hundred sixteen patients with gastrointestinal diseases were studied. Among 32 with Crohns disease, only 2 (6.1%) produced methane, as well as 16 of 51 ulcerative colitis patients (31.4%) and 11 of 32 patients with the irritable bowel syndrome (34.4%). Breath methane is thus unusual in Crohns disease. After bowel cleansing for colonoscopy or surgery, 15 of 18 methane producers became nonproducers, whereas after antibiotic treatment, 24 of 30 producers sustained their methane-producing status. After gentamycin and cephazolin therapy, methane production was abolished in three of eight patients. Slight spontaneous variations in methane production were also noticed with two of 23 control subjects, becoming nonproducers on restudy after 10–25 months. Thus gastrointestinal diseases, bowel cleansing and, to a much lesser degree, antibiotic therapy, affect methane production.

Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones

Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days +/- 0.7) as from patients with stones (2.4 days +/- 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.

Cholesterol-phospholipid vesicles in human bile: an ultrastructural study

Phospholipid vesicles, a newly described (bile salt independent) mode of cholesterol transport in human bile, were previously characterized by quasi-elastic light scattering and gel filtration. In the present study the ultrastructure of these vesicles was investigated by electron microscopy using freeze-fracture and negative-staining techniques. Vesicles of varying size were found in all 14 hepatic and 3 gallbladder biles examined. The diameter of the vesicles ranged from 25 to 75 nm by electron microscopy after freeze fracture and from 54 to 94 nm by quasi-elastic light scattering. They had a spherical shape and appeared to be unilamellar. The appearance of the vesicles in fresh hepatic and gallbladder biles as well as in chromatographic fractions was similar. Vesicles were dissolved by the addition of exogenous bile salts. Cholesterol is transported in human bile by both vesicles and micelles. The role of the vesicles may be particularly important in preventing cholesterol precipitation in dilute and supersaturated biles.

Crohn's Disease in the Jewish Population of Tel-Aviv-Yafo: Epidemiologic and Clinical Aspects

A survey of the incidence and prevalence of Crohns disease in the Jewish population of Tel-Aviv-Yafo was carried out from 1970 to 1976. The annual incidence rate was 1.28, and the prevalence was 12.31 per 10(5) population. The prevalence of 16.69 per 10(5) population among Ashkenazi jews was significantly higher than that found in non-Ashkenazi Jews, 4.19 per 10(5) population. Even so, Crohns disease is significantly less common in Tel-Aviv than outside Israel, according to most recently published surveys. Similarly, the complication, surgery, and mortality rate are less marked than those reported from other studies. These figures confirm the authors impression that inflammatory bowel disease in general is less common and possible less severe in Tel-Aviv than in the United State and Western Europe. The strikingly higher prevalence in the Ashkenazi community, especially in the Israeli-born population, suggests a hereditary predisposition. The apparent differences among Askhenazi Jews in various parts of the world may relate to environmental factors.