Vitamin intervention on precancerous lesions of the esophagus in a high-risk population in China.
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Clinical Trials as Topic↗
Biomedical subjects
M Crespi
Publications and source records attributed to M Crespi.
Nutritional and haematological status of Chinese farmers: the influence of 13.5 months treatment with riboflavin, retinol and zinc.
A retinol (15 mg), riboflavin (200 mg) and zinc (50 mg) supplement or a placebo (D-mannitol) was given to 610 Chinese farmers weekly for 13.5 months. Riboflavin, retinol, beta-carotene, tocopherol and zinc status were measured in all subjects at the start and end of the intervention and in a subsample at 2 months. Plasma vitamin C, haemoglobin and haematocrits were measured on other subsamples at the end of the supplementation period. At the start vitamin A, zinc and riboflavin status were poor. Plasma retinol and zinc concentrations were higher in men than women but the opposite was observed with respect to beta-carotene. There was no difference between the sexes for tocopherol and riboflavin. Tocopherol:cholesterol ratios suggested vitamin E status was good and vitamin C status also appeared adequate. The supplement increased plasma retinol throughout the whole period but riboflavin status improved only over the first 2 months and then remained constant. Plasma zinc increased in both treatment and placebo groups by approximately 15 to 20 per cent in men and women. Mean concentrations of retinol and tocopherol and beta-carotene (in women only) increased by approximately 20 per cent in the placebo group. It is argued that seasonal factors and/or the placebo may have been responsible for the increase in retinol and beta-carotene in the placebo group. The lack of an increase in beta-carotene in the men may have been due to their higher retinol requirements. Lastly, the increase in retinol may have been responsible for the increase in tocopherol and zinc in plasma since these nutrients increased in those whose plasma retinol increased, irrespective of treatment.
Adult↗
Hot maté drinking and precancerous lesions of the oesophagus: an endoscopic survey in southern Brazil.
Thermal injury resulting from drinking very hot beverages has been incriminated as a risk factor for oesophageal cancer, although no information is available on the lesions caused by this injury in human or experimental animals. The drinking of hot maté tea is very common in areas of moderately high incidence of oesophageal cancer in south-eastern areas of South America. This study investigated the prevalence of precancerous lesions of the oesophagus in 60 unskilled male workers, of whom half were daily maté drinkers and the remainder were non-maté drinkers. These 2 groups were matched for age, smoking and alcohol intake. Maté drinkers were 2.2 times more likely (p = 0.046) to develop histologically confirmed oesophagitis than non-maté drinkers.
Adult↗
Comparison of once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of duodenal ulcer. A multicenter, double-blind, controlled study.
A multicenter, double-blind, randomized, controlled study was conducted in 234 duodenal ulcer patients to compare the efficacy and safety of the H2-receptor antagonists famotidine and ranitidine in the treatment of duodenal ulcer. Patients received 40 mg famotidine (119 patients) or 300 mg ranitidine (115 patients) once daily at bedtime for 4 weeks. If ulcer lesions persisted, treatment was extended to 6 weeks. Efficacy was assessed by relief of symptoms and endoscopic findings of ulcer healing. Safety was determined on the basis of reports of side effects, results of laboratory tests, and, in selected patients, changes in plasma levels of hormones. The 4- and 6-week healing rates achieved with famotidine were 76% and 91%, respectively, and with ranitidine they were 76% and 87%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly, both drugs provided satisfactory relief of pain and dyspeptic symptoms. However, famotidine produced significantly (P less than 0.05) greater relief of postprandial fullness and heartburn. The incidence of untoward effects was low in both treatment groups, and abnormal results in laboratory tests were observed in only one patient, a chronic alcoholic receiving famotidine, who withdrew from the study because of a slight elevation in serum transaminase levels. One patient in the ranitidine treatment group dropped out of the study because of a generalized urticarial rash; however, a causal relationship between drug and effect could not be established. The authors conclude that famotidine may be regarded as the best alternative to ranitidine in the treatment of duodenal ulcer.
Adolescent↗
N-nitrosamine formation by microorganisms isolated from human gastric juice and urine: biochemical studies on bacteria-catalysed nitrosation.
Twelve out of 14 bacterial strains isolated from patients with urinary infections and nine out of 30 microorganisms isolated from gastric juice from patients with gastric achlorhydria were shown to catalyse the formation of N-nitrosomorpholine (NMOR) from nitrite and morpholine at neutral pH. The effects of various metal ions and cofactors on the bacterial nitrosation reaction was investigated. The presence of nitrate in the culture medium was required to induce nitrosating activity in bacteria, but low nitrate concentrations inhibited the nitrosation reaction.
Escherichia coli↗
Effect of riboflavin, retinol, and zinc on micronuclei of buccal mucosa and of esophagus: a randomized double-blind intervention study in China.
A randomized double-blind intervention trial was done in Huixian, People's Republic of China, a population with a high incidence of esophageal cancer. The aim of the trial was to determine whether a once-a-week treatment with retinol (15 mg or 50,000 IU), riboflavin (200 mg), and zinc (50 mg) could result, after 1 year, in a lower prevalence of precancerous lesions of the esophagus in the group receiving the active treatment as compared with the prevalence in the group receiving a placebo. The results of the trial, published elsewhere, indicated that the treatment had no effect on the prevalence of precancerous lesions of the esophagus. In determining whether an effect could be detected when earlier end points are used, the prevalence of micronuclei was evaluated in exfoliated cells from the esophagus and from the buccal mucosa in the present study. In a subsample of 200 out of the original 610 study subjects, smears were taken from the buccal mucosa before and after treatment, and in 170 subjects esophageal smears were obtained during endoscopy only after treatment. The smears were fixed and kept at room temperature over 1 year before being evaluated for the presence of micronuclei by means of 4'-6-diamidino-2-phenylindole fluorescent staining. Smears from approximately half of the subjects were considered suitable for evaluation. No statistically significant difference in the prevalence of micronuclei in the buccal mucosa cells was observed before and after treatment (the mean percentage of micronucleated cells in the vitamin group upon first examination, before treatment started, 0.35%; 1 year after treatment, 0.31%) or between the treatment and the placebo group at the final examination. (The mean percentage of micronucleated cells in the vitamin-treated group was 0.31 and 0.39% in the placebo group.) However, a statistically significant reduction (P = .04) was observed in the prevalence of micronuclei in esophageal cells in the treatment group as compared to the placebo. (The mean percentage of micronucleated cells in the vitamin-treated group was 0.19%; it was 0.31% in the placebo group.
Adult↗
Intragastric nitrosation and precancerous lesions of the gastrointestinal tract: testing of an etiological hypothesis.
The N-nitrosoproline (NPRO) test was used to study whether subjects with precancerous conditions of the stomach have an elevated potential for endogenous nitrosation. The highest yield of NPRO after ingestion of beetroot juice (as a source of nitrate) and proline was seen in subjects whose pH of fasting gastric juice was about 1.5-2. No increased level of NPRO was detected in subjects with more advanced lesions, compared to those with a normal stomach. Counts of total and nitrate-reducing bacteria were positively correlated with the pH of gastric juice but did not correlate with the urinary level of NPRO in the same individuals. Bacteria and intragastric nitrosation are discussed as possible etiological factors in human stomach cancer.
Adult↗
Rapid purification of topoisomerase I from human breast cancer cells by high-performance liquid chromatography.
The DNA regulatory enzyme topoisomerase I (TpI) from human breast cancer cells has been analyzed by high-performance liquid chromatography (HPLC) for the first time. Cells were homogenized in Tris buffer and TpI activity was extracted with 0.5 M sodium chloride. Negatively supercoiled plasmid pBR322 was used as the substrate to monitor TpI activity, as judged by relaxed products, analyzed on 1% agarose gels. HPLC in the anion-exchange mode (HPIEC) provided an approximately 6-fold purification of the enzyme. Enhanced purification was subsequently obtained by chromatography of a HPIEC eluate on size-exclusion columns (30- to 60-fold). Recovery of TpI from size-exclusion columns, whether used in multistep analysis or as the first step, was dependent on inclusion of organic solvent, 1-propanol (0.5%, v/v), in the mobile phase. Marked resolution of TpI activity was observed with HPIEC on a SynChrom CM-300 column. Enzyme activity was noted in the void volume, at 150-200 mM phosphate and at 250-350 mM phosphate. TpI purification was 10- and 120-fold in the latter two peaks, respectively. Silver-stained polyacrylamide gels of TpI-containing activity, eluted from a CM-300 column, showed considerable purification of all but the void volume fraction. A distinct protein band at approximately 88-90 kD was seen in the peak eluted from the CM-300 column with 250-350 mM phosphate. These results indicate that HPLC is useful for rapid purification of the labile enzyme, TpI, in the analysis of its structure-function relationship.
Breast Neoplasms↗
Urinary N-nitrosamino acids as indices of endogenous formation of N-nitroso compounds.
Exposure to their precursors (e.g., amines, nitrate/nitrite, NOx) can lead to formation in the human body of N-nitroso compounds (NOC), a class of potent animal carcinogens, which are also suspected of being carcinogenic in man. A non-invasive method, the 'N-nitrosoproline (NPRO) test', for estimating endogenous nitrosation in man was developed in our laboratory. This test, which monitors 24-hr-excretion of urinary N-nitrosamino acids, is now applied in clinical and field studies, with the aim of measuring nitrosamine exposure and of identifying dietary, life-style, and host factors, or disease states, that affect nitrosation in man. Results from such studies are used to identify populations/individuals at high risk for cancers of the stomach, oesophagus, and oral cavity possibly caused by endogenous nitrosamines, and to indicate preventive measures by which the body burden of endogenous nitroso carcinogens can be lowered efficiently.
Amino Acids↗
Effect of interferon on Vero cells persistently infected with SSPE virus and lytically infected with measles virus.
The effect of lymphoblastoid interferon (IFN) on viral polypeptides synthesized in a Vero cell culture persistently infected with subacute sclerosing panencephalitis virus (SSPE-Vero) was compared to that of Vero cells infected with exogenous measles virus. After IFN treatment there was no significant decrease in the synthesis of SSPE viral proteins, but inhibition of synthesis of measles polypeptides was readily seen. In Vero and SSPE-Vero cells IFN was able to inhibit replication of Sindbis virus although the effect in Vero cells was significantly more sensitive. In both cell lines IFN was able to stimulate 2'--5' oligoadenylate synthetase (E enzyme) but not the protein kinase system. The SSPE-Vero cells showed a lower basal level of E enzyme activity than the Vero cells.
2',5'-Oligoadenylate Synthetase↗
The use of interferon functional assays in the laboratory monitoring of patients with hepatocellular carcinoma receiving interferon.
Patients with hepatocellular carcinoma receiving recombinant leukocyte alpha interferon therapy were monitored using a series of assays to evaluate various components of the interferon system. Pretherapy serum interferon concentrations were not elevated significantly in these patients, although elevated levels were recorded after initiation of therapy. Both before and after interferon treatment, the peripheral blood leukocytes of the patients were shown to be capable of producing both gamma and alpha interferon when appropriately stimulated in vitro. The patients' peripheral blood leukocytes also responded to interferon therapy, with 85% resisting viral replication after treatment was initiated. However, interferon did not appear to be of therapeutic value in these patients.
Adult↗
Cancer mortality in the Republic of San Marino.
San Marino is a small independent Republic encircled by Italy, with a population of approximately 20,000. It still maintains an ethnic profile favoured by a tendency to genetic segregation due to endogamy. Since 1908 detailed data have been kept on all deaths among residents also for those dying outside the country. In this study the mortality trends based on crude rates are reported for all neoplasms and for selected sites in the years 1908 to 1980, showing increased rates for all neoplasms and the highest rate for stomach cancer. Age-adjusted death rates were calculated for all neoplasms and for selected sites, by sex, in the years 1966 to 1980. Stomach cancer was the commonest cause of cancer death in San Marino and its age-adjusted death rate was the highest in the world. A sharp increase was also observed for respiratory tract and colorectal cancers in recent years.
Female↗
Molecular cloning of rotavirus genome.
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Animals↗
Proliferative abnormalities of the oesophageal epithelium of Chinese populations at high and low risk for oesophageal cancer.
Studies on the pattern of proliferation of epithelial cells from the oesophagus of 33 individuals from Linxian, a high-risk area for oesophageal cancer in China, and of 22 subjects from Jiaoxian, a low-risk area for the same cancer in China, were performed using thymidine labelling. Oesophageal biopsies were obtained during endoscopic surveys carried out in these 2 populations. A clear difference was observed between the 2 groups; the high-risk group showed cell proliferation in the upper layers of the epithelium more often than the low-risk group. No difference was found in the cell proliferation patterns of subjects with oesophagitis and those without oesophagitis in the high-risk area. This finding could suggest that the tritiated thymidine assay may be a more sensitive method to characterize the precancerous lesions of the oesophagus in high- and low-risk populations than simple histological evaluation.
Adult↗
No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China.
A randomised double-blind intervention trial was carried out in Huixian, Henan Province, People's Republic of China, to determine whether combined treatment with retinol, riboflavine, and zinc could lower the prevalence of precancerous lesions of the oesophagus. 610 subjects in the age group 35-64 were randomised to receive once a week the active treatment (15 mg [50 000 IU] retinol, 200 mg riboflavine, and 50 mg zinc) or placebo. Both at entry to the study and at the end of the treatment, 13.5 months later, the subjects were examined, with an emphasis on signs of vitamin A and riboflavine deficiences, and riboflavine, retinol, beta-carotene, and zinc levels were measured. Compliance was excellent. The final examination, on 567 (93%) subjects, included oesophagoscopy and at least two biopsies. The intervention did not affect the prevalence of oesophageal lesions: after one year, the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3% in the placebo group and 48.9% in the vitamin/zinc treated group.
Adult↗
Comparison of riboflavin, vitamin A, and zinc status of Chinese populations at high and low risk for esophageal cancer.
In two surveys in The Peoples Republic of China, blood samples were collected for nutritional studies in two counties where the risks of esophageal cancer are very different. The first survey was done in May 1980 in Linxian County (Henan Province) where the risk of esophageal cancer is very high. Blood samples were obtained from 111 persons (58 men, 53 women) who were selected randomly from 528 subjects that underwent endoscopical examination. The second survey was done in May 1981 in Jiaoxian County (Shandong Province) where the risk of esophageal cancer is reported to be relatively low. Blood samples were obtained from 120 persons (66 men, 54 women) who were selected randomly from 252 subjects that had also had undergone endoscopy. The blood samples were used to measure the nutritional status of riboflavin (erythrocyte glutathione reductase activation coefficient), vitamin A (retinol and carotene concentrations), and zinc (plasma and hair zinc concentrations). Only riboflavin status was significantly different in the two communities. The distribution of erythrocyte glutathione reductase activation coefficient values suggested that riboflavin status was much better in the low-risk community. Also in May 1981, a few more blood samples were obtained from some of the participants of the previous year's study in Linxian. A slight improvement in riboflavin and zinc status was detected. We considered the possibility that these changes may have been linked to the socioeconomic changes currently taking place in rural areas. Data were also collected from food allocation records in 15 production brigades in Linxian and 13 production brigades in Jiaoxian in the same years. The records used represented the food consumption of 3,491 and 2,552 persons, respectively, and were used to calculate daily food and nutrient intakes in the two communities. Dietary analyses highlighted the vegetarian nature of the diet, the low consumption of riboflavin, and the virtual dependence on carotene for vitamin A. Both communities consumed very little in the way of animal products or fruit, but intake of these items was higher in Jiaoxian.
China↗
Monitoring of urinary mutagenicity in workers exposed to low doses of 2,4,7-trinitro-9-fluorenone.
A monitoring of the urinary mutagenicity in workers occupationally exposed to low doses of 2,4,7-trinitro-9-fluorenone (TNF) was undertaken. Urine concentrate of 22 exposed workers (11 smokers and 11 nonsmokers) and 18 presumedly unexposed workers (7 smokers and 11 nonsmokers) were assayed for mutagenicity in Salmonella typhimurium strain TA98 with the plate incorporation technique. In this test system none of the urine concentrate was effective as a mutagen, either in the absence or presence of S9. Fifteen urine samples (8 from exposed workers, 7 from referents) were also tested in the microtiter fluctuation assay. With this technique smoking habits were significantly related to urinary mutagenicity in tests performed with metabolic activation. In neither case however was the association between presumed exposure and urinary mutagenicity significant. These results were evaluated on the basis of urinary mutagenicity data obtained from rats exposed to TNF by different routes. It was shown that the observed urinary mutagenicity accounts for a minor fraction of the administered TNF dose (about 0.1 to 0.2%, depending on the route of exposure); thus it is possible that low-level exposure to TNF could escape detection by urinary mutagenicity monitoring.
Air Pollutants, Occupational↗
Precursor lesions of oesophageal cancer in a low-risk population in China: comparison with high-risk populations.
An endoscopic survey was undertaken in Jiaoxian, People's Republic of China, a population at low risk for oesophageal cancer, to determine the prevalence of precancerous lesions of the oesophagus, and this rate was compared with the prevalence observed previously in high-risk populations in Iran and Linxian, China. The study involved 252 subjects whose exposure to suspected risk factors was determined by a questionnaire and all of whom underwent physical examination and oesophagoscopy, including cytology and biopsy. Chronic oesophagitis, with endoscopic and histologic characteristics similar to those observed in the high-risk populations of Iran and Linxian, was found in 28% of the study subjects compared to 80% in Iran and 65% in Linxian. Oesophagitis accompanied by atrophy of the epithelium was found in 0.4% compared to 10.5% in Iran and 10.8% in Linxian. No case of dysplasia was diagnosed in Jiaoxian while this condition was diagnosed in 4% of the subjects examined in Iran and in 8% of those in Linxian. The findings suggest that these lesions are in fact precancerous. Vitamin analysis showed that riboflavin deficiency was widespread in Jiaoxian, as in Iran and Linxian, but was more severe in Linxian than in Jiaoxian. No significant difference was found in the mean levels of retinol, beta-carotene and zinc between the two populations.
Adolescent↗