Internal medicine curriculum reform.
Explore the source record for details and available documents.
Internal Medicine↗
Biomedical subjects
M Lipkin
Publications and source records attributed to M Lipkin.
Modulation of colonic epithelial cell proliferation, histone acetylation, and luminal short chain fatty acids by variation of dietary fiber (wheat bran) in rats.
The effect of increasing amounts of wheat bran (0, 5, 10, 20%) in AIN-76 semisynthetic diet on colonic luminal short chain fatty acids, epithelial cell histone acetylation, and cytokinetics, was studied for 2 weeks in groups of 10 male Sprague-Dawley rats. Luminal contents were removed from the colon at sacrifice, quick frozen, and analyzed for short chain fatty acids by gas-liquid chromatography. Histone acetylation was assessed in cells isolated from the same animals. Cell proliferation was measured after a short pulse in vivo with [3H]thymidine. Colonic luminal butyrate levels were lower in the 0 and 20% fiber groups, and higher in the 5 and 10% fiber groups. In contrast, cell proliferation, as determined by labeling index, was higher in the 0 and 20% fiber groups, and lower in the 5 and 10% fiber groups. This resulted in a significant inverse correlation between luminal butyrate levels and colonic cell proliferation. In addition, there was a positive linear correlation between luminal butyric acid levels and colon epithelial cell histone acetylation. From these data it was concluded that colonic butyrate levels can be modulated by the addition of wheat bran to the diet and that butyrate can modulate DNA synthesis (calculated as labeling index) in the proliferative compartments of colonic crypts. The localization of dividing cells was unchanged and no induction of terminal differentiation was detectable (contrary to what has been observed for transformed cells in culture).
Acetylation↗
Calcium, vitamin D, and colon cancer.
Calcium contributes to the progression of epithelial cells through all phases of the proliferative cycle and into stages of cell differentiation; intracellular concentrations of calcium that are required for cell renewal, however, are lower than those required for epithelial-cell differentiation. These effects of calcium are modulated by interactions with 1,25-dihydroxy-vitamin D3, phosphate, and fatty acids, all of which are partly dependent on dietary intake. In rodent models, increased dietary calcium inhibited hyperproliferation of colon epithelial cells induced by increased levels of fatty acids or bile acids present in the colon. When carcinogens induced hyperproliferation of colon epithelial cells the hyperproliferation was decreased by added dietary calcium, and in several animal models the occurrence of carcinogen-induced carcinomas of the colon decreased with increased dietary calcium. A nutritional stress diet, designed to represent human Western dietary intake of calcium, phosphate, vitamin D, and fat, produced hyperproliferation and hyperplasia in the colons of rodents; these effects were reduced by increasing dietary levels of calcium. Decreased levels of ornithine decarboxylase also were reported in human and rodent colon mucosa exposed to increasing levels of calcium. In human subjects at increased risk for familial colon cancer, hyperproliferation of colon epithelial cells was reduced after oral dietary supplementation with calcium. In epidemiological studies, several investigators reported inverse correlations between levels of dietary calcium intake and the incidence of colon cancer. Extrapolation of the data have suggested a protective effect of total calcium intakes above 1500 to 1800 mg/day.
1,2-Dimethylhydrazine↗
Gastrointestinal cancer: pathogenesis, risk factors and the development of intermediate biomarkers for chemoprevention studies.
Dietary, environmental and genetic factors contribute to the etiology, pathogenesis and risk for gastrointestinal cancers. Measurements of cell proliferation and differentiation further identify abnormal cellular properties associated with increased susceptibility to gastrointestinal cancer. In precancerous esophagus, the proliferative compartment increases in size, increased ploidy and dysplasia develop, and epithelial cells express abnormal cytokeratins and ectopic tumor-associated antigens. In precancerous stomach, increased proliferative activity and metaplasia develop. Intestinal enzymes and mucins are expressed and normal gastric antigens are replaced by intestinal or embryonic antigens. In flat colonic mucosa and in colonic adenomas, expansions of the proliferative compartment occur. Gene expression is modified, gene deletions occur and blood group-related antigens are modified as the cells undergo abnormal differentiation and develop into adenomas and carcinomas. Chemopreventive regimens are now being tested to determine whether they modify such intermediate biomarkers toward normal levels characteristic of lower risk for neoplasia. It is anticipated that the utilization of intermediate biomarkers in chemoprevention studies may permit more novel chemopreventive regimens to be tested in human subjects than heretofore was possible.
Anticarcinogenic Agents↗
Intermediate biomarkers of increased risk for colorectal cancer: comparison of different methods of analysis and modifications by chemopreventive interventions.
Intermediate biomarkers of abnormal cell growth and development have recently been used in chemoprevention trials in attempts to identify the efficacy of chemopreventive agents in human subjects. Measurements carried out include those related to cell proliferation, differentiation, and gene structure and expression in the colon. Among modified patterns of cell proliferation identified by microautoradiographic or immunoperoxidase assays, a characteristic expansion in the size of the proliferative compartment has been observed in normal-appearing colorectal mucosa of human subjects with disease increasing cancer risk; the same patterns have been induced by chemical carcinogens in rodents. Moreover, this intermediate biomarker has been modulated by chemopreventive agents in both rodents and humans. Newer intermediate biomarkers being studied for application to human chemopreventive programs include normal and abnormal patterns of expression of mucins, intermediate filaments and cytoskeletal proteins, and the structure and expression of a variety of genes associated with normal and abnormal cell development. The application of these various intermediate biomarkers to chemoprevention studies is increasing the ability of investigators to analyze the effects of novel chemopreventive agents in the colon and in other organs.
Anticarcinogenic Agents↗
Precancerous lesions of the human esophagus: multiparametric study of esophageal biopsies from a high-risk population in Linxian, China.
Histopathology, morphometry, tritiated thymidine incorporation and immunohistochemistry were studied in 221 esophageal biopsies from subjects with cytologica hyperplasia in Linxian, China. A spectrum of 7 morphologic entities were found: (1) normal/near normal (NN); (2) basal cell hyperplasia 0 (BHO); (3) simple hyperplasia (SH); (4) mixed basal and spinous cell hyperplasia (MBS); (5) basal cell hyperplasia 1 (BH1); (6) dysplasia (D); and (7) non-proliferative lesion (NP). Forty percent of the biopsies had combinations of histologic types. The thickness of the epithelium was increased in SH, MBS, and BH1, but not in BHO and NP. Elongation of papillae was frequently seen in SH, MBS, BH1, and D. Papillary bleeding was very prevalent in the esophageal specimens studied. A variety of cellular changes were found in peripapillary areas especially when bleeding occurred. [3H]-thymidine labeling index was dramatically increased in the entire epithelium in dysplasia, and also increased in cell layer 3 of MBS, BH1 and D. Blood group antigen LeY and lectin WGA showed consistent positivity in cellular membranes of the squamous cells, and these changes occurred before gross morphologic alterations. These findings provide a hypothesis for the sequence of pathogenetic events leading to esophageal carcinoma, and define each step with corresponding biomarkers for cancer prevention studies.
Biopsy↗
The potential for using non-physicians to compensate for the reduced availability of residents.
Both the number of residents and the amount of time existing residents have in which to carry out their activities may soon be decreasing. To consider the potential for alternative ways of staffing teaching hospitals, it is necessary to know how residents spend their time. The authors sought to learn this by conducting a time-motion study of eight internal medicine residents at two urban hospitals in New York City in 1988. The residents' activities were observed and coded by premedical students, and the authors independently classified the possible activities into (1) those that had to be done by a physician, (2) those that were educational only, and (3) those that could be done by a non-physician. A total of 1,726 activities of 67 kinds were coded, averaging 7.75 minutes each. The authors analyze and project their data using two models--the traditional model of care in which the physician is the primary medical manager of the patient, and an alternative model in which a midlevel practitioner, such as a nurse practitioner, would perform the day-to-day monitoring of patients. For example, the data indicate that in the traditional model, almost half of a resident's time is spent in activities that must be done by a physician, meaning that another kind of physician would be needed to do those activities if the resident were unavailable; but in the midlevel practitioner model, only around 20% of the activities would require a physician. The authors give detailed breakdowns of their data, estimate the kinds and numbers of non-physician health care professionals necessary to substitute for residents in appropriate activities, and review possible difficulties in implementing such substitutions.
Evaluation Studies as Topic↗
The California Family Health Project: I. Introduction and a description of adult health.
Little research has addressed patterns of family and health relationships that reflect both the scope and complexity of family life and the breadth and diversity of health. In the first of a series of articles, we describe the California Family Health Project, a study in which four large "domains" of family life (Structure/Organization, World View, Problem Solving, and Emotional Management) were mapped, described, and compared with a large battery of adult health measures. We first present a brief critical overview of the literature on family and health research, then explain our rationale, define our approach to the multivariate analysis of family and health data, and describe our sample of 225 community-based families. To prepare for analyses with the family variables, we next present descriptive data based on separate principal components analysis (PCA) and multidimensional scaling analysis (MDS) of 14 self-reported health scores for husbands and for wives. No grouping or clustering of health variables emerged for either husbands or wives in the PCAs. A two-dimensional MDS analysis for husbands and for wives displayed the health variables in a circular pattern in which no predominant descriptive dimension or group of discrete dimensions emerged. Consequently, we decided that all 14 health scores will be used in the analyses, with the family variables to follow.
Adult↗
Doctor-patient communication: the Toronto consensus statement.
Explore the source record for details and available documents.
Canada↗
Calcium, vitamin D, and colon cancer.
Explore the source record for details and available documents.
Calcium↗
Patterns of gene expression that characterize the colonic mucosa in patients at genetic risk for colonic cancer.
We have used a computer-driven scanning and image-processing system to identify a panel of 30 cDNA clones whose pattern of expression in individual biopsy specimens distinguishes the flat, normal-appearing colonic mucosa of patients in two genetic groups at high risk for development of colorectal cancer from that of normal colonic mucosa in low-risk individuals. The two high-risk groups, familial adenomatous polyposis and hereditary nonpolyposis colon cancer, are indistinguishable based on the pattern of expression of the 30 selected clones. This suggests that the extensive pleiotropic effects of the inherited loci, which may play an important role in the mechanism of increased risk and early onset of the disease, are similar in these populations.
Adenomatous Polyposis Coli↗
Correlations between rectal mucosa cell proliferation and the clinical and pathological features of nonfamilial neoplasia of the large intestine.
An in vitro study of proliferative activity as shown by immunohistochemical detection of the uptake of bromodeoxyuridine was run on rectal biopsies from 400 patients with nonfamilial large bowel neoplasia: 200 adenoma; 150 adenocarcinoma; 50 adenoma plus adenocarcinoma. The controls were 400 subjects with negative personal and family histories of colorectal neoplasia. The number and height distribution of bromodeoxyuridine positive cells were determined by dividing the crypt into five longitudinal compartments. The total labeling index and the labeling index of each compartment were higher in all three groups compared with the controls. In subjects with adenoma, total labeling index and labeling index values were correlated with tumor size and decreased in function of the duration of the polyp-free colon state. The major zone of DNA synthesis had shifted to the intermediate and surface crypt compartments in all three groups. This stage II abnormality was more marked in adenoma patients with a high degree of dysplasia and in those with adenoma plus adenocarcinoma. Hyperproliferation and the proliferative compartment shift are cytokinetic abnormalities that coexist in the flat rectal mucosa of patients with colorectal neoplasia. Nonetheless, they are independent, controlled by different factors, and are expressions of different biological aspects of large bowel carcinogenesis.
Adenocarcinoma↗
Lectin soybean agglutinin: measurements in colonic epithelial cells of human subjects following supplemental dietary calcium.
A biomarker of cell differentiation was analyzed in normal and abnormal colonic epithelial cells. Soybean agglutinin (SBA) lectin which binds to specific carbohydrate residues was studied in normal human colonic epithelial cells, in epithelial cells in transitional colonic mucosa adjacent to carcinomas, and in colonic carcinomas. Findings revealed that increased SBA binding occurred maximally in normal, well-differentiated colonic epithelial cells, and least in colonic carcinomas. Further quantitation of SBA lectin binding also was carried out before and after supplemental dietary calcium. Findings revealed that in subjects whose colonic crypt biopsies had normal SBA lectin binding before calcium supplementation, SBA remained unchanged after calcium supplementation. However, in subjects whose biopsies initially had reduced SBA binding, the SBA increased after calcium and became more characteristic of that observed in normal colonic epithelium. In subjects receiving calcium for less than 3 months, the increased SBA was not statistically significant; but when subjects received calcium for durations of 3 months or longer SBA lectin binding was significantly increased, changing towards that observed in normal mucosa containing greater numbers of well-differentiated colonic epithelial cells.
Adenocarcinoma↗
Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective.
In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized.
Animals↗
Colonic hyperproliferation induced in rats and mice by nutritional-stress diets containing four components of a human Western-style diet (series 2).
In a previous study colonic hyperplasia and hyperproliferation were induced in mice and rats by a nutritional-stress diet, based on the AIN-76A semisynthetic diet modified to contain four suggested high-risk components of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D contents. In this study the effect of raising calcium alone to near the median level (0.22 mg/kcal) and to a high level (1.3 mg/kcal), comparable to adult human dietary intake, was tested in mice and rats while retaining the three other high-risk components. With median calcium intake the nutritional-stress diet induced hyperproliferation of epithelial cells in colonic crypts, with increased numbers of proliferating cells in crypt columns in sigmoid colon of mice (P less than 0.001) and rats (P = 0.02) and in the ascending colon of mice (P = 0.01). With high calcium intake, hyperproliferation was reduced almost to control amounts in the presence of unchanged fat, phosphate, and vitamin D.
Animals↗
Sex differences in patients' and physicians' communication during primary care medical visits.
This study reports on the analysis of audiotapes of 537 adult, chronic disease patients and their 127 physicians (101 men and 26 women) in a variety of primary care practice settings to explore differences attributable to the effects of the patient's and the physician's sex on the process of communication during medical visits. Compared to male physicians, women conducted longer medical visits (22.9 vs 20.3 minutes; F(1,515) = 7.9, P less than .005), with substantially more talk F(1,518) = 19.5, P less than .000. Differences were especially evident during the history segment of the visit when female physicians talked 40% more than male physicians (F(1,518) = 20.1, P less than .000) and when patients of female physicians talked 58% more than male physicians' patients (F(1,448) = 24.4, P less than .000). Compared to male physicians, female physicians engaged in more positive talk, partnership-building, question-asking, and information-giving. Similarly, when with female compared to male physicians, patients engaged in more positive talk, more partnership-building, question-asking, and information-giving related to both biomedical and psychosocial topics.
Adult↗
Intermediate biomarkers and studies of cancer prevention in the gastrointestinal tract.
Explore the source record for details and available documents.
Animals↗
Labeling index and labeling distribution of cells in esophageal epithelium of individuals at increased risk for esophageal cancer in Huixian, China.
The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation observed in normal esophagus, in hyperplasia, in mild dysplasia, and in moderate dysplasia in a total of 118 subjects. The amount of cell proliferation observed was lowest in normal esophageal epithelium and increased progressively in subjects having hyperplasia, mild dysplasia, and moderate dysplasia. The location of proliferating cells was limited mainly to the base of the esophageal epithelium in normal esophagus, but expanded toward the surface of the esophageal lining in individuals with hyperplasia and dysplasia. The larger total numbers of proliferating cells in the esophageal epithelium and the progressive expansion of the proliferative compartment toward the epithelial surface found in hyperplasia and in dysplasia could both facilitate the screening of subjects for esophageal cancer risk and serve as intermediate biomarkers in prophylactic dietary or pharmacological intervention studies.
Cell Count↗