[Aspirin and the gastric mucosa--a new look at an old problem].
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Animals↗
Biomedical subjects
Z Fireman
Publications and source records attributed to Z Fireman.
[Congestive gastropathy in liver cirrhosis].
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Humans↗
Malabsorption due to a ventral hernia.
A case of malabsorption due to a stagnant loop which occurred in a huge ventral hernia is presented. The clinical course was relatively indolent with symptoms of malabsorption and occasional abdominal pain. Although rare, abdominal hernia can lead to malabsorption due to bacterial overgrowth as a result of stagnant loop.
Aged↗
Screening for colorectal neoplasia: a multicenter study in Israel.
We report the design and results of the first Israeli multicenter screening program for colorectal neoplasia. The screening protocol comprised a risk questionnaire, fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. A total of 5,601 individuals were screened in five medical centers, 55% being asymptomatic with low or average risk. Colorectal tumors were found in 12.3% of screenees, the majority being adenomas. The risk for large bowel neoplasia was greatest in persons with a personal history of colorectal neoplasia (neoplasia rate 473.2/10(3)) and was increased in those with inflammatory bowel disease, a family history of colorectal tumor, or past history of cured breast cancer. European-born Jews had a 50% greater risk than non-European-born Jews. Persons at high risk were more likely to return for repeat screening than those at low or average risk. However, approximately 15% of persons at high risk actually thought that they were of average risk. Fecal occult blood testing was markedly less reliable than flexible sigmoidoscopy and had a false-negative rate of 84.4%. The results demonstrate that existing medical facilities in Israel can be used to screen at least those individuals with increased risk for colorectal neoplasia.
Adenoma↗
Rectal epithelial proliferation in persons post sporadic colorectal neoplasia.
Some studies have shown diffuse large bowel epithelial hyperproliferation in persons having colorectal neoplasia. Thus, measurements of rectal epithelial proliferation (REP) could be useful as a screening biomarker of risk for sporadic neoplasia. We examined REP, by autoradiography with tritiated thymidine, in 84 persons: 32 healthy volunteers, 37 who had had sporadic adenomas and 15 post cured sporadic colorectal cancer. Measurements of the labelling index (ratio of labelled to total number of crypt cells) showed a statistically insignificant but increasing gradient of hyperproliferation related to degree and invasiveness of neoplasia. However, this became significant when examining the proportion of labelled crypt compartments in each group and by comparing combined compartments 3 and 4 of cancer patients to non-cancer patients. Gender and age were found to be parameters that influenced the results. Using standard methods of analysis of REP, the lack of clear separation between risk groups limits the usefulness of REP measurements as a screening biomarker of risk for sporadic large bowel neoplasia.
Adenocarcinoma↗
Rectal epithelial proliferation in women recovered from breast cancer.
Women recovered from breast cancer are at increased risk for colorectal neoplasia. The reasons may be genetic, dietary or endogenous hormonal risk factors. Measurements of rectal epithelial proliferation are a useful biomarker of risk for large bowel cancer. This was studied in 12 women after (mean 7.8 years) cured breast cancer, who had a mean % labelling index of 7.5 +/- 3.5 (S.D.) as compared to 5.8 +/- 1.8 (S.D.) in a disease-free comparison group of 25 women. In addition, analysis of labelled crypt compartments demonstrated a significantly higher proportion in the study group with thymidine uptake, mainly in the mid crypt zone, and an extension of crypt cell DNA synthesis towards the surface epithelium. Using proliferative activity as a biomarker of risk in a larger study group, we may learn more about common etiological factors for both malignancies and also identify a higher-risk subgroup for long-term follow-up and possible therapeutic intervention.
Aged↗
Rectal epithelial proliferation characteristics of first degree relatives of sporadic colon cancer patients.
Hyperproliferation of rectal epithelium is characteristic of families at high genetic risk for large bowel neoplasia, but has not been well-documented in families of sporadic colorectal cancer patients. This was studied in 119 such first degree relatives and 44 comparison subjects without this family history. All screened negative for large bowel neoplasia. Within the family group proliferation was significantly higher in the men and those aged less than 45 years, also higher (insignificantly) in non-Europeans and those having greater than 1 first degree colorectal cancer relative. In comparison to the nonfamily group the labelling index (LI) of the relatives showed a significant negative correlation with age (R = -0.20, P = 0.03). Within this family group the probability of having an elevated LI (greater than 6.0%) was greatest in the young (less than 50 years old) men (odds ratio = 2.0). Measurements of rectal epithelial proliferation (REP) in these first degree relatives, at a young age, might help delineate a high risk subgroup for prospective primary and secondary intervention.
Adult↗
Effect of a calcium-enriched diet on the colonic epithelial hyperproliferation induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats on a low calcium and fat diet.
We examined whether hyperproliferation of colonic crypt epithelium during cancer induction by N-methyl-N-nitro-N-nitrosoguanidine (MNNG), in rats on a low fat and calcium diet could be reduced by added calcium p.o. From the age of 4 weeks, 104 male Sprague-Dawley rats received a low fat (3.5%), low calcium (0.05% calcium ion), and low vitamin D (0.4 IU/g) diet. Sixty-four also had calcium salts, derived from either calcium lactate or solubilized calcium carbonate, added to their drinking water; therefore their total calcium intake was about 1% of daily diet. At age 12 weeks the rats were divided into 4 treatment groups: 8 rats, not receiving added calcium, had rectal saline instillations weekly (saline control group) and were sacrificed after a further 28 weeks; 3 groups of 32 rats each received intrarectal MNNG (1.5 mg) weekly. One group, not receiving added calcium, was the MNNG control group; while the second group also received added calcium lactate, and the third group received calcium carbonate. Groups of 24 were sacrificed periodically until 28 weeks of treatment. Rats were sacrificed and epithelial proliferation was estimated, 1 week after the last intrarectal instillation, by in vivo labeling with tritiated thymidine and measuring the ratio of labeled to total colonic crypt epithelial cells. The mean labeling index of the MNNG treated and added calcium groups were significantly higher (8.7-9.5%) than that of the saline controls (2.8%) only at week 28; however, it was then still significantly less than that of the MNNG controls not having added calcium (17.9%). Hyperproliferation, during induction of colonic cancer by MNNG in rats on a low calcium diet, can be reduced by a calcium enriched diet even in the presence of a low fat intake.
Animals↗
[Screening for colorectal neoplasms].
We screened groups at high risk for colorectal neoplasms, determining the efficacy of the leukocyte adherence inhibition test (LAI) for early detection, in comparison with that of the fecal occult blood (Hemoccult) test and sigmoidoscopy or colonoscopy. Those screened included 549 first-degree relatives of patients with colorectal cancer, 190 patients with a past history of colorectal adenoma or carcinoma and 67 with a past history of breast or gynecological cancer or inflammatory bowel disease. 146 normal volunteers served as controls. In 782 of those fully screened during a 3-year period, 121 had adenomas (15.5%) and 5 had invasive cancer (0.6%). The LAI test was positive in 21% of those at high risk and in 7.5% of the controls. The hemoccult test was positive in only 4.8%, but in 1/3 of them neoplasms were found. This predictive value of 33% compares with only 16% for the LAI test. That most of the neoplasms found were adenomas and not invasive cancer may be due to the relative youth of most of those screened. We conclude that the groups studied were indeed at high risk. The LAI test is not sensitive enough to identify benign adenomas but might serve as another risk-market for colorectal neoplasms. Long-term follow-up of those at high-risk with positive LAI tests may prove that we have identified a subgroup truly at risk.
Adenoma↗
Influence of demographic parameters on rectal epithelial proliferation.
Measurement of rectal epithelial proliferation is now being used as a biomarker for assessing risk for colorectal cancer and response within dietary intervention studies. We examined the possible confounding effects of demographic parameters on the proliferation of 52 healthy middle-aged volunteers without known risk factors for colorectal cancer. No significant effects on proliferation of age, sex or ethnic grouping were found other than marked urban-rural differences amongst men. We hypothesise that these could be explained by differences in dietary habits and their deleterious effects in the older male population. Careful matching of controls are probably needed in order to demonstrate the minor changes in mucosal proliferation that could reflect risk for neoplasia. Further human studies are needed to examine the effects of diet and extremes of age on proliferation.
Adult↗
Reproducibility studies and effects of bowel preparations on measurements of rectal epithelial proliferation.
Measurements of rectal epithelial proliferation (REP), using tritiated labelled thymidine, correlate with colonic epithelial proliferation, risk for cancer and response to therapies. There have been criticisms regarding its reproducibility and the possible deleterious effects of bowel preparations on this biomarker. We studied paired observations on 7 patients repeated without bowel preparation, 11 repeated after tap-water enema, and 8 repeated after PEG-electrolyte solution or extract of senna purgative and found no significant differences between paired observations. In addition, in a high-risk group for colorectal cancer, 31 persons received PEG or senna preparation and their REP was not significantly different from that of 23 examined without these preparations. Thus, REP is a reproducible biomarker and not affected by several commonly used bowel preparations.
Biopsy↗
A comparison of metronidazole and sulfasalazine in the maintenance of remission in patients with ulcerative colitis.
In a double-blind, randomized trial, we tested the effectiveness of metronidazole (0.6 g/day) against sulfasalazine (2 g/day) in the maintenance of remission in patients with ulcerative colitis. The patients were in remission for 1-11 months at entry to trial, which lasted for 12 months. Forty patients entered the trial and 33 completed it. Metronidazole was found to be slightly more effective than sulfasalazine, a difference statistically significant only at 12 months. Six patients also completed a crossover trial. Remission was maintained for 12 months in 3 patients by metronidazole and in none of the 6 by sulfasalazine. No significant side effects were noted, and in particular, no paresthesias were reported. This trial, as well as our previous one, suggests that metronidazole may be useful in the maintenance of remission in patients with ulcerative colitis, but that it is ineffective in the therapy of the acute attack.
Clinical Trials as Topic↗
Oral calcium suppresses increased rectal epithelial proliferation of persons at risk of colorectal cancer.
Dietary calcium may inhibit colonic carcinogenesis promoted by high fat, phosphate, and low fibre diets. In persons at risk for colon cancer oral calcium supplements significantly suppress increased rectal epithelial proliferation. This was studied in a cohort of 35 volunteers: 26 first degree relatives of colorectal cancer patients and nine who had had colonic adenomas (mean age 51.6 years, 17 (49%) men, all negative for large bowel neoplasia). 1.25-1.5 g elemental calcium was given in divided daily doses for three months. Rectal pinch biopsies were taken without bowel preparation, before and mean 8.4 weeks during and 7.2 weeks after treatment and incubated with tritiated thymidine. The mean number of labelled cells, as a ratio of the total number of crypt cells (labelling index-LI), and their crypt position, were determined. The mean number of labelled cells decreased during treatment by 29%, especially in the basal three-fifths of crypts. There was also a significant 10% increase in mean number of crypt cells during treatment. [Mean LI decreased by 36% (p less than 0.001) during calcium treatment and almost returned to basal values after cessation.] If a raised LI is a marker of potential malignancy and a randomised clinical trial confirms that calcium suppresses it, dietary intervention studies in high risk persons are indicated.
Administration, Oral↗
Intestinal cancer in patients with Crohn's disease. A population study in central Israel.
A population study of Crohn's 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.
Adolescent↗
Epidemiology of ulcerative colitis in the Jewish population of central Israel 1970-1980.
The epidemiology of ulcerative colitis (UC) was studied in the Jewish population of central Israel in a densely populated urban area of more than 1,400,000 inhabitants. The mean annual incidence for the years 1970-80 was 3.86/100,000, 3.94 in males, and 3.79 in females. The incidence rose from 2.67 in 1970 to 5.09 in 1979, the rise being similar in both sexes. This rise in incidence was found in 3 separate localities in the study area inhabited by communities of different extraction and age composition. The disease started most frequently between the ages of 25 and 29. The crude prevalence of UC in 1980 was 55.2/100,000. The age-adjusted prevalence in Israel-born Jews was 45.8, in Asia-Africa-born 48.5 and in Europe-America-born 52.7/100,000. Compared with our previous study in 1960-70 in the city of Tel Aviv-Yafo, the prevalence of UC was increased and the differences between the community groups have narrowed. This suggests an effect of environmental factors in the causation of ulcerative colitis.
Adolescent↗
Epidemiology of Crohn's disease in the Jewish population of central Israel, 1970-1980.
The epidemiology of Crohn's disease (CD) during the years 1970-80 was studied in the Jewish population in a defined area of central Israel with 1.4 million inhabitants. Three hundred sixty-five patients with definite CD were identified, and a complete follow-up was obtained. The incidence of CD rose from 0.33 (per 10(5)) in 1970 to 3.10 in 1979. This rise was noted in both sexes, in all age groups, in all major Jewish community groups, and was demonstrated in three different regions of the study area. It is thought to represent a true (10-fold) increase in incidence. The mean annual incidence was 1.55/10(5). The prevalence in 1970 was 7.08/10(5), and in 1980 it was 19.47/10(5). In 1970, the age-adjusted prevalence in immigrants from Europe-America was 13.27 and in immigrants from Asia-Africa it was 1.69. In 1980, the difference between the two groups narrowed and the prevalences were 26.05 and 12.37, respectively. This decrease in differences between original migrant groups, as well as the rapid changes in incidence, point to the effect of environmental factors in the pathogenesis of CD. Population studies worldwide have demonstrated an increased incidence of CD in Jews, with marked differences among Jews in different geographic areas. This suggests the coexistence of genetic and environmental factors in the pathogenesis of the disease.
Adult↗
Colorectal cancer in patients with ulcerative colitis. A population study in central Israel.
The incidence of colorectal cancer was studied in an unselected group of 1035 patients (total group) with ulcerative colitis and in a subgroup of 822 who resided, at the time of diagnosis, within a defined area in central Israel (regional group). The operation rate was 5.2% and the follow-up period (mean +/- SD) was 11.5 +/- 8.3 yr, range 1-52 yr. The cumulative incidence of colorectal cancer in all patients was 0.2% at 10 yr, 2.8% at 15 yr, 5.5% at 20 yr, and 13.5% at 30 yr. The ratio of observed to expected cancer was 0.9 at 10 yr, 5.0 at 20 yr, and 6.4 at 30 yr. The cancer incidence was 1 case per 3895 patient-years in the first decade of disease, 1 case per 198 patient-years in the second decade, and 1 case per 100 patient-years in the third decade. All these figures were higher in patients with total colonic involvement. There were no significant differences between the total and regional patient groups. Onset of ulcerative colitis in the first and second decade of life was not associated with a higher cancer incidence when standardized for extent and duration of disease. The risk of colorectal cancer in patients with ulcerative colitis was more strongly expressed in population groups with a lower incidence of this cancer. The cumulative incidence of colorectal cancer in ulcerative colitis is much lower in population-based studies than that reported from major medical centers. Worldwide this incidence may also vary among different populations.
Adult↗
The relative value of fecal occult blood tests and flexible sigmoidoscopy in screening for large bowel neoplasia.
The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P greater than 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.
Adult↗