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M Lipkin

Publications and source records attributed to M Lipkin.

At least 55 records · Page 3Linked to original sources
PubMed1996

Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon.

In this study, feeding Western-style diets (WDs) to mice for a duration of two years without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dysplastic crypts and focal hyperplasias with or without atypical nuclei. To better understand early biological events contributing to the development of colonic neoplasia, grossly normal colonic mucosa was investigated; mitotic and apoptotic colonic epithelial cells, atypical mitosis, and atypical nuclei were studied. A significant and transient increase of mitotic activity in the basal and intermediate portions of the colonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epithelial cells. In the middle of the rodents' life span, after administration of both the WDs and control diet, the rodents developed a marked depletion of apoptotic epithelial cells in the mid-region of the colonic crypts; this was followed by the expansion of an epithelial cell population containing atypical nuclei, and the emergence of the gross lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced single-crypt dysplastic lesions and focal hyperplasias indicative of tumorigenesis.

Animals↗
PubMed1996

Cytokeratin, lectin, and acidic mucin modulation in differentiating colonic epithelial cells of mice after feeding Western-style diets.

Several studies have recently reported the development of colonic epithelial cell hyperproliferation in rodents following the ingestion of Western-style diets. In this study, additional measurements related to differentiation and maturation of the colonic epithelial cells were made after feeding this type of diet. Two Western-style diets high in fat and phosphate content and low in calcium and vitamin D were fed to C57BL/6J mice for 12, 24, and 52 weeks. Diet A contained American Blend fat as a source of lipids, diet B contained corn oil, and control diet C was a standard AIN-76A semisynthetic diet which is lower in fat content and higher in calcium and vitamin D. Colonic epithelial cells were studied for three biomarkers: cytokeratin catalogue no. 18 (clone LE64) expression, soybean agglutinin carbohydrate lectin binding, and acidic mucins including sialo- and sulfomucins. Feeding of diets A and B revealed that colonic epithelial cells had increased expression of cytokeratin catalogue 18 and SBA carbohydrate lectin binding compared to controls (P = 0.0001 for diet A versus C and diet B versus C). Significant differences were found between diets B and C (P = 0.0001) and diets A and C (P = 0.0001) in total acidic mucins and in the ratio of sialomucin:sulfomucin (P = 0.0001). These findings demonstrate that both functional and structural modifications occurred in colonic epithelial cells under these dietary conditions, and further defined this rodent model for preclinical evaluation of nutritional and chemopreventive interventions.

Animals↗
PubMed1996

Genetic screening for colorectal cancer and intervention.

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.

Clinical Trials as Topic↗
PubMed1996

Strategies for intervention with chemopreventive agents.

Different mechanisms of activity have led to the development of a wide variety of intermediate biomarkers to measure the efficacy of chemopreventive agents. Chemopreventive agents are now being used in pre-clinical models that have targeted mutations or normal cells. Based on pre-clinical findings, clinical chemoprevention studies have progressed to measure the possible modulation of dysplastic lesions, including adenomas. Human studies are best carried out where the study design matches the known activity of the agents on cells in early, mid- or late stages of abnormal cellular development, previously determined in pre-clinical studies.

Animals↗
PubMed1996

Inherited and acquired risk factors in colonic neoplasia and modulation by chemopreventive interventions.

The progressively abnormal development of epithelial cells prior to tumor development leads to widely differing chemopreventive approaches. The diversity of these approaches has resulted in different assays to measure the activities of the agents. To apply these assays to preclinical studies, we have developed rodent models in which different stages of evolution of colonic neoplasia are expressed. In one model mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc 1638 mice). These mice develop multiple gastrointestinal lesions including adenomas and carcinomas, focal areas of high grade dysplasia (FAD) and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc 1638 mice on a Western-style diet, compared to Apc 1638 mice on AIN-76A diet which has lower fat content and higher calcium and vitamin D. These studies have also been carried out in normal mice, and have demonstrated without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Modulation of cell proliferation has also been induced by Western-style diets in other organs including mammary gland, pancreas and prostate. These findings are leading to the development of new preclinical models for evaluating the efficacy of many classes of chemopreventive agents.

Animals↗
PubMed1996

Physician-patient interaction in reproductive counseling.

OBJECTIVE: To review the scientific and clinical bases for effective patient counseling in contraceptive care. DATA SOURCES: All articles and chapters in the Annotated Bibliography of Doctor Patient Communication of the Task Force on Doctor and Patient of the American Academy on Physician and Patient were searched and included. This is an expert-derived data base based on MEDLINE review from 1969 to 1994 and including expert-selected additions from PsychLit and a variety of other social science data bases, books, and reviews. METHODS OF STUDY SELECTION: Expert consensus was used from the Committee on Bibliography of the American Academy on Physician and Patient. TABULATION, INTEGRATION, AND RESULTS: The doctor-patient interaction is the main determinant of the accuracy and completeness of patient data, diagnostic accuracy, efficiency in the encounter, compliance, patient understanding of problems, and patient and physician satisfaction. Yet this critical skill is inadequately taught and practiced, with serious consequences for patient care and physician job satisfaction. Use of the 14 structural elements (preparing the environment, preparing oneself, observation, greeting, introduction, detecting and overcoming barriers to communication, surveying problems, negotiating a priority problem, developing a narrative thread, establishing the life context of the patient, establishing a safety net, presenting findings and options, negotiating plans, and closing) and three functions (gathering information, developing a therapeutic relationship, and patient education) and their associated behaviors improves encounter results significantly. Other helpful activities are patient activation, facilitating partnership, review of findings and plans, eliciting and responding to patients' attitudes and emotions about contraception and fertility, and use of empathy and positive regard. CONCLUSIONS: The use of scientifically derived, empirically validated interview skills substantially improves outcomes in contraceptive and other patient education and counseling. Use of appropriate structure and functions of the encounter, patient participation and partnership, review of patient understanding and reactions, and relating to the patients' attitudes and emotions about the subject each improve the outcomes of contraceptive care.

Contraception↗
PubMed1996

Patient education and counseling in the context of modern patient-physician-family communication.

The modern understanding of patient education derives from a robust literature from public health and clinical medicine that started to become empirical and rigorous in the mid-1960s. Patient education is one of three functions of the medical interview, each of which must each be accomplished skillfully if the others are to be maximally effective. This article discusses the new conceptualization of patient education and provides examples of how it works. The rule of patient activation is discussed and implications for future research are presented.

Clinical Competence↗
PubMed1996

Absence of germline mutations in exons 5-9 of the p53 gene in patients with Li-Fraumeni-like (SBLA) and familial adenomatous polyposis heritable cancer syndromes.

Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li-Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984,1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP. DNA sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF from SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusion, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established.

Adenomatous Polyposis Coli↗
PubMed1996

Model of mouse mammary gland hyperproliferation and hyperplasia induced by a western-style diet.

Mammary glands of female C57BL/6J mice were analyzed after they were fed a Western-style diet or control AIN-76A diet. The Western-style diet contained several risk factors found in human diets in geographic regions having increased risk for breast cancer: high fat and phosphate and low calcium and vitamin D. After they were fed these diets for 8, 14, and 20 weeks, mice were sacrificed, and mammary glands were removed for morphometric and radioautographic measurements. Although after the animals were fed the Western-style diet for 8 weeks the number of terminal ducts per mouse mammary gland (NTDMG) was similar in the Western-style and control diet groups, after they were fed the Western-style diet for 14 weeks (p < 0.05) and 20 weeks (p < 0.01) the NTDMG significantly increased compared with the control group. Moreover, there was a significant increase (p < 0.01) in the tritiated thymidine labeling index of mammary terminal ductal epithelial cells after 14 and 20 weeks of Western-style diet administration. Thus the Western-style diet induced increased epithelial cell proliferation and increased NTDMG in female mice when fed during young adult growth and development. The findings raise the possibility that the ingestion of a diet with Western-style fat and phosphate content and with low calcium and vitamin D may induce similar changes during the early development of the human mammary gland.

Animals↗
PubMed1996

Fecal and rectal mucosal diacylglycerol concentrations and epithelial proliferative kinetics.

Fecal diacylglycerol (DAG) concentrations have been suggested as biomarkers for colonic neoplasia because of their potential to be absorbed in the colon and to stimulate epithelial cell proliferation. The interrelationships among nutrient intake, fecal and mucosal DAG, and colonic proliferative markers have not previously been studied. We designed a pilot study to evaluate the feasibility of evaluating these interrelationships in 12 volunteers who had a history of colonic adenomatous polyposis. Total mucosal DAG concentrations were not related to fecal DAG concentrations, but mucosal DAG correlated inversely with the whole crypt labeling index. Dietary intake did not alter fecal DAG concentrations. However, the percentage of calories from dietary fat correlated positively with the whole crypt labeling index. Fiber and calcium intake showed a positive correlation with the labeling index in the upper 40% of the crypt. The present pilot study failed to demonstrate a correlation between dietary components and fecal and total mucosal DAG. Additional studies relating fecal DAG with mucosal proliferation will require the evaluation of DAG concentrations in subcellular compartments of mucosal cells and/or measurement of fecal DAG fatty acid composition.

Adenomatous Polyposis Coli↗
PubMed1995

Calcium and the prevention of colon cancer.

Chemoprevention studies utilizing calcium have now progressed from basic measurements to clinical trials. Calcium's effects on epithelial cells have demonstrated decreased proliferation and induced cell differentiation with increasing levels of calcium in vitro, similar in vivo effects in rodent and human colon, and decreased carcinogen-induced colonic tumor formation in rodents. Current studies are attempting to inhibit colonic adenoma formation in human subjects. Most but not all epidemiologic studies also link increased dietary calcium with a decreased risk of colon cancer. In animal models, supplemental dietary calcium has decreased mammary epithelial cell hyperplasia and hyperproliferation and colonic cell hyperproliferation when the latter was induced by bile acids, fatty acids, and partial resection of the small intestine. Supplemental dietary calcium also decreased carcinogen-induced colonic tumors in several rodent models. In normal mice, and in mice carrying a targeted apc gene mutation, we recently increased colonic polypoid hyperplasias by a Western-style diet containing low calcium and vitamin D. In human subjects at increased risk for colon cancer, oral calcium supplementation significantly reduced colonic epithelial cell proliferation in most of the studies, including four randomized clinical trials. These studies have now progressed to short-term human clinical trials, including trials that measure the regrowth of transformed adenoma cells. Short-term adenoma-regrowth clinical trials, however, are limited in their ability to measure whether chemopreventive agents inhibit early genotoxic events, abnormal cellular metabolic activities involved in tumor promotion over many years, or the progression of adenoma cells to carcinoma.

Adenoma↗
PubMed1995

Learners as teachers: the conflicting roles of medical residents.

OBJECTIVE: To explore the impact of internal medicine residents' roles as learners, teachers, and physicians on their performance in teaching and supervising interns; to generate insights for educational policy and research. DESIGN: Qualitative analysis of in-depth, semistructured, recorded interviews with a cohort of second-postgraduate-year (PGY-2) residents. Questions elicited their accounts of differences in the learning process between the first and second residency years, their responses to situations in which they lacked sufficient clinical knowledge, their views of their supervisory relationship with interns, and their assessments of changes in their role in patient care since their internships. Transcripts were independently analyzed by the interdisciplinary team of authors. SETTING: New York University/Bellevue Hospital Center's internal medicine residency (New York City), a highly competitive program in a major public hospital and a university medical center, emphasizing housestaff autonomy and self-reliance. PARTICIPANTS: A cohort of 18 of 21 medical residents at Bellevue Hospital Center during the last rotation of PGY-2. RESULTS: Intense conflicts confound residents' roles as teachers. These conflicts fall into three categories: 1) as learners, residents' own needs frequently coincide with those of interns in ways that may undermine their teaching--they are expected to nurture others despite their own considerable needs for emotional support, teach material that they barely grasp, and exert authority while feeling ignorant; 2) as team leaders, residents must ensure that interns get the hospital's work done, sometimes at the expense of teaching them; and 3) as clinicians, residents' first priority is to address the medical needs of patients--the learning needs of interns are secondary. CONCLUSION: Second-year internal medicine residents experience conflicts inherent in their simultaneous commitment to learning, teaching, and service that may undermine both their effectiveness in supervising interns and their own professional development. Potential remedies are to restructure residency programs so as to equip residents with training and support for their role as teachers, reduce the tension between training and service by delegating tasks to nonphysician personnel, and provide graded responsibility to housestaff as physicians and teachers.

Attitude of Health Personnel↗