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Biomedical subjects

H Farbstein

Publications and source records attributed to H Farbstein.

15 recordsLinked to original sources

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients.

BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS: Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.

Adenoma↗

CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus cnf (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study.

A multicenter phase III randomized study compared the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer. The standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), was administered to 77 women. The experimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mitoxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Follow-up of the 145 patients by six participating hospitals showed no statistically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly alopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage II breast cancer.

Adult↗

The role of nutritional habits during gestation and child life in pediatric brain tumor etiology.

Our aim was to evaluate the role of maternal nutritional habits during the period of gestation and of children subsequent diet in the etiology of pediatric brain tumors. All cases of incident nervous system tumors under age 18, diagnosed between 1984 and 1993 (n = 300) in Israel were identified. Two matched population controls per case were selected (n = 574). Personal interviews, using a semi-quantified three-step food frequency questionnaire, were performed. Univariate analysis showed that increased child consumption of vegetable fat [p trend 0.01; 95% confidence interval (CI) 1.1-3.2], carbohydrates (p trend 0.05; CI 1.0-5.9), and vitamin E (p trend 0.05; CI 1.0-3.3), were significantly associated with brain tumor risk. No associations were found with nitrate, nitrite or vitamin C. A significant positive association with potassium consumption (p trend 0.01; CI 1.1-3.7) was noted during gestation. Results of multivariate analysis showed that the only persisting associations were with vegetable fat (OR = 1.36; CI 1.06-1.73) in the child diet and potassium intake during gestation (OR = 1.44; CI 1.04-1.99). In conclusion, nutritional associations with pediatric brain tumor etiology, remain unsubstantiated.

Adolescent↗

Use of sunscreen is linked with elevated naevi counts in Israeli school children and adolescents.

Epidemiological evidence indicates that a fair complexion and exposure to solar radiation in early years contribute to the proliferation of naevi and subsequent melanoma risk. To determine whether protection from sunlight is associated with lower naevi counts, we examined the prevalence and risk factors of naevi in a sample of Israeli school pupils. Whole body counts of naevi were recorded in 974 out of 1312 (74.2%) recruited pupils (7 and 12 year olds) from Ramat-Gan and Jerusalem. Host characteristics and habits of sun exposure were obtained using questionnaires. In each age group and geographic area, the mean whole body naevi counts, adjusted for confounders, were higher among males, pupils of European-American descent, and those susceptible to sunburn. The contributions to naevi risk of fair skin colour and frequent recreational sun exposure were higher among 7 year olds. Regular sunscreen use contributed to the naevi risk for both age strata in Ramat-Gan (at age 7, rate ratio [RR] = 1.7, 95% confidence interval [CI] = 1.3-2.2; at age 12, RR = 1.5, 95% CI = 1.1-2.1). Among the younger age group in Ramat-Gan, even seldom compared with no use of sunscreen was associated with higher naevi counts (RR= 1.5, 95% CI = 1.2-2.0). Similar patterns were noted with the pupils from Jerusalem. In conclusion, the elevated naevi count with increased sunscreen use indicates that sunscreens apparently do not modify the genetic predisposition to naevi proliferation. For better protection of children and adolescents, including those who use sunscreens, from the naevogenic effect of solar radiation, they should be encouraged to limit their exposure and wear protective clothing when in the sun.

Adolescent↗

Changes in cytokine production of breast cancer patients treated with interferons.

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.

Antineoplastic Agents, Hormonal↗

Modified cuspal relationships of mandibular molar teeth in children with Down's syndrome.

A total of 50 permanent mandibular 1st molars of 26 children with Down's syndrome (DS) were examined from dental casts and 59 permanent mandibular 1st molars of normal children were examined from 33 individuals. The following measurements were performed on both right and left molars (teeth 46 and 36 respectively): (a) the intercusp distances (mb-db, mb-d, mb-dl, db-ml, db-d, db-dl, db-ml, d-dl, d-ml, dl-ml); (b) the db-mb-ml, mb-db-ml, mb-ml-db, d-mb-dl, mb-d-dl, mb-dl-d angles; (c) the area of the pentagon formed by connecting the cusp tips. All intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to design a multivariate probability model for DS and normals. A model based on 2 distances only, mb-dl and mb-db, proved sufficient to discriminate between the teeth of DS and the normal population. The model for tooth 36 for example was as follows: p(DS) = (e(30.6-5.6(mb-dl)+25(mb-db)))/(1 + e(30.6 5.6(mb-dl)+25(mb db))). A similar model for tooth 46 was also created, as well as a model which incorporated both teeth. With respect to the angles, significant differences between DS and normals were found in 3 out of the 6 angles which were measured: the d-mb-dl angle was smaller than in normals, the mb-d-dl angle was higher, and the mb-dl-d angle was smaller. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in the DS population.

Adolescent↗

Preillness non dietary factors and habits in inflammatory bowel disease.

AIM: Environmental as well as genetic factors play a role in the pathogenesis of inflammatory bowel diseases. The effects of smoking and diet have been demonstrated. Other factors have not been extensively investigated. PATIENTS: Preillness non dietary habits and factors were studied in 88 patients with recent onset of inflammatory bowel diseases (55 with ulcerative colitis and 33 with Crohn's disease) and in matched 76 population and 68 clinic controls. RESULTS: No significant differences were found in relation to education, housing, birth weight, breast feeding in infancy and current weight. The current body mass index was significantly lower in patients as compared to clinic controls (p < 0.05). More patients had low levels of physical activity during the preillness period as compared to controls (p < 0.001 vs clinic controls), while more controls engaged in moderate (p < 0.05) or high levels of physical activity in the corresponding periods. Patients spent fewer hours in strenuous physical activity as compared to controls (NS). Patients slept fewer hours per day (p < 0.05 vs clinic controls). More patients than controls experienced stressful life events during the year prior to onset of symptoms (p < 0.05 for patients with Crohn's disease against both controls and all patients vs population controls). CONCLUSIONS: Other environmental factors besides smoking and diet may affect the pathogenesis of inflammatory bowel disease.

Adolescent↗

Nutritional and lifestyle habits and water-fiber interaction in colorectal adenoma etiology.

Adenomatous polyps are neoplasms that may progress to colorectal cancer. The role of diet and other lifestyle habits in their etiology is now being elucidated. The aim of this study was to evaluate effects of nutritional habits, weight and weight gain, tobacco smoking, and physical activity in adenoma etiology. A quantified dietary history questionnaire was designed to evaluate long-term dietary habits in addition to more recent ones. The study population comprised 196 adenoma patients and matched asymptomatic, screened controls. Statistical analysis used multivariate conditional logistic models, adjusting for total energy intake and physical activity. Odds ratios (ORs) and 95% confidence intervals (CIs) for adenoma associated with highest versus lowest tertiles of mean daily intake were as follows: for energy, OR 3.7 and CI 2.1-6.7; for animal fat, OR 2.4 and CI 1.2-4.7; for tobacco smoking, OR 3.1 and CI 1.1-2.8; and for weight gain, OR 2.2 and CI 1.2-4.1 (P for linear trend for all, < or = 0.01). Significant negative associations were found with intake of total carbohydrates (OR, 0.3; CI, 0.1-0.7) and fluids (OR, 0.4; CI, 0.2-0.8) (P for both < 0.01) as well as for physical activity (OR, 0.6; CI, 0.3-0.9; P = 0.03). Increased risk for adenoma was observed with decreased intake of carotene (OR, 0.6; CI, 0.3-1.0; P = 0.06), vitamin E (OR, 0.6; CI, 0.3-1.0; P = 0.07), and dietary fiber (OR, 0.6; CI, 0.3-1.3; not significant). The OR of interaction between water and dietary fiber was significant (OR, 0.7; CI, 0.6-0.9; P = 0.01), suggesting a synergistic protective effect. Specific dietary and lifestyle habits were identified as independent factors associated with colorectal adenomas; of special interest is the interaction between water and fiber intake. Avoiding these factors might delay or prevent neoplasia.

Adenoma↗

Contribution of cardiopulmonary indices in the assessment of patients with silent and symptomatic ischemia during exercise testing.

Cardiopulmonary and radionuclear indices were used to evaluate and compare cardiac function during exercise testing in patients with symptomatic and silent ischemia. The study comprised 58 patients aged 35-74 years, divided into three groups: Group I-20 patients (controls) with neither ST depression nor chest pain; Group II-22 patients with ST depression > 1 mm and no chest pain; Group III-16 patients with both ST depression and chest pain. All patients in Groups II and III demonstrated significant coronary artery disease. No antianginal medication was taken at least 24 h before testing. All patients underwent a cardiopulmonary exercise test and a multigated acquisition radionuclear study. The following variables were measured: oxygen consumption (VO2), CO2 output (VCO2), minute ventilation (VE), O2-pulse, ventilatory anaerobic threshold (VAT), left ventricular ejection fraction (LVEF) at rest (r) and at maximal effort (ex). Probability values were significant for all variables (P < 0.01-0.0001) except left ventricular ejection fraction-rest (P not significant between the three groups). No significant differences in extent of coronary artery disease were noted between Groups II and III. These findings suggest that during exercise testing patients with silent ischemia have better overall cardiac function than patients with symptomatic ischemia. Their value for both cardiopulmonary and radionuclear indices are closer to those of the control group than to the symptomatic group, regardless of the severity of the coronary artery disease Summary of results: (mean +/- 1 S.D.) Group VO2-max O2-Pulse max VAT (%) VAT (ml/min) LVEF-rest delta LVEF (ex-r) I 25.2 +/- 6.3 15.7 +/- 3.4 51.2 +/- 6.6 1075 +/- 289 54.7 +/- 7 5.4 +/- 4.85 II 22.4 +/- 2.8 14.5 +/- 2 47.0 +/- 5.3 854 +/- 136 52 +/- 10 1.2 +/- 6.7 III 16.0 +/- 2.5 11.4 +/- 2 41.6 +/- 7.7 683 +/- 105 51 +/- 8.5 -5.87 +/- 6.3

Adult↗

Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression.

PURPOSE: Superficial bladder carcinoma, treated by resection and intravesical administration of bacillus Calmette-Guérin (BCG), yields a remission rate that approaches 70%. We examined whether expression of interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) genes can serve to predict response. PATIENTS AND METHODS: During BCG treatment, we analyzed induction of IL-2 and IFN-gamma mRNA in peripheral-blood mononuclear cells (PBMC) from 73 patients: 51 with papillary tumors and 22 with carcinoma-in-situ (CIS). Results were correlated with remission, relapse, or tumor persistence over a 4-year follow-up period. RESULTS: Independent of tumor type, induction of IL-2 mRNA was observed for patients who responded with remission, but not for those who relapsed (P = .0001). Multivariate logistic analysis showed that inducibility of IL-2 mRNA is the discriminating parameter, which yields a predictive value of 97% for remission. Of 23 patients with relapse/persistence, 22 lacked inducibility of IL-2 mRNA (sensitivity, 95.6%), while 35 of 50 patients in remission exhibited inducibility (specificity, 70%). For patients with carcinoma-in-situ, in which remission or failure depends solely on response to BCG, sensitivity and specificity were 88% and 86%, respectively; for patients with papillary tumors, they were 100% and 64%. IFN-gamma mRNA, by contrast, was clearly inducible in PBMC from all patients (P = .51). The disease-free interval increased progressively with inducibility of IL-2 mRNA; this trend was highly significant (P = .0001). CONCLUSION: IL-2 gene expression is essential for mounting an antitumor response in superficial bladder carcinoma. Inducibility of IL-2 mRNA is an independent prognostic parameter and useful predictive indicator of remission versus relapse.

Adjuvants, Immunologic↗

Modification of tooth size and shape in Down's syndrome.

Individuals with Down's syndrome (DS) tend to display a reduction in size of permanent teeth, and reduced intercuspal distances in molars. A total of 51 permanent maxillary 1st molars of 26 DS children were examined from dental casts, 65 permanent maxillary 1st molars of normal children were examined from dental casts of 33 individuals. The following measurements were performed on both right and left molars (teeth 16 and 26 respectively): (1) all intercusp distance (distobuccal, db; distolingual, dl; mesiobuccal, mb; mesiolingual, ml); (2) the db-mb-ml, mb-db-ml, db-ml-mb, dl-mb-db, mb-dl-db, and dl-db-mb angles; (3) the area of the quadrangle shaped by connecting the cusp tips. All the intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to build a multivariate probability model for DS and normals. The mb-dl and mb-ml distances of the upper right molar (tooth 16) were sufficient to discriminate between DS and normal teeth: [table: see text] The probability for DS is higher when mb-ml is relatively higher in the mb-ml/mb-dl ratio. Another logistic analysis based on groups of angles revealed a combination of 3 angles which gave highly statistically significant discrimination between both groups: the mb-db-dl angle was higher in DS, the mb-dl-db angle was slightly smaller in DS, and the mb-ml-db angle was slightly smaller in DS. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in DS population. Our probability model for DS teeth is simple and practical because it requires only 2 intercusp distances to be put into the formula.

Adolescent↗

Neu differentiation factor (heregulin) induces expression of intercellular adhesion molecule 1: implications for mammary tumors.

Neu differentiation factor (NDF, also called heregulin) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu/HER-2 receptor and induces phenotypic differentiation of certain mammary cancer cell lines to growth-arrested and milk-producing cells. To determine which molecules participate in the concomitant morphological alterations, we analyzed the expression of several cytoskeletal and surface molecules and found that NDF elevated the expression of the intercellular adhesion molecule 1 (ICAM-1) in cultured AU-565 human adenocarcinoma cells. The levels of both the protein and the mRNA of ICAM-1 were elevated after 3-5 days of treatment with NDF. Elevated expression of ICAM-1 was induced also by gamma-interferon and by the tumor-promoting phorbol ester (PMA), albeit with different kinetics. Down-regulation of protein kinase C or its inhibition by calphostin C partially inhibited the effect of NDF, implying that the induction of ICAM-1 may be mediated by protein kinase C. NDF transcripts were detectable in 3 of 9 human mammary tumors, suggesting that the in vitro effect of the factor may be relevant to breast cancer. By selecting Neu-positive human mammary tumors (n = 39), we found a significant correlation (P < 0.001) between the expression of ICAM-1 and histological features of invasive ductal carcinoma with a prominent carcinoma in situ component. When cultured in vitro the cells of these tumors grew in clusters and formed domelike structures reminiscent of comedo-type carcinoma in situ. In addition, the majority of patients with tumors that coexpressed ICAM-1 and Neu had no lymph node involvement, unlike most Neu-positive but ICAM-1-negative tumors, which metastasized to the lymphatic system. Taken together, our observations suggest that the induction of ICAM-1 by NDF may affect the morphology, differentiation state, and metastasis of Neu-expressing mammary tumor cells.

Adenocarcinoma↗

[Evaluation of non-occurrence by TI-59 programmable calculator].

A TI-59 programmable calculator program is presented for calculating either risk probability, sample size or confidence level (given 2 of the 3 variables) in cases in which an event of concern did not occur, or as expressed mathematically, had zero numerators. Its main usefulness is as a tool for interpreting previously published data containing no adverse event of concern while contemplating medical alternatives. These conditions are not infrequent in rare medical events--either diseases or complications. However, applicability of the program extends beyond these confines, exemplified in experimental planning for considering expected sample size or in calculating certainty in terms of confidence level.

Mathematical Computing↗

Significance of the magnitude of a QS wave deflection in evaluating the uninvolved muscle in anterior wall myocardial infarction.

The significance of dynamic changes of the QS wave magnitude, as demonstrated in the precordial leads, within the natural evolution of acute anterior wall myocardial infarction (AAMI) was assessed in 25 patients within two weeks of their admission to the intensive cardiac care unit. Two sets of tests, including 12-lead electrocardiogram and a full radionuclear study, were performed in two time periods: (1) within the first 48 hours of admission; and (2) between the 12th and 15th day after admission. Comparison and correlation between the electrocardiographic data, QS waves in leads V2 and V3 and in V1 to V6 (sigma QV2-3 and sigma QV1-6), and radionuclear regional ejection fractions of the noninfarcted posterior muscle (inferior, infero-apical, and posterolateral regions and posterior index) were done. Significant linear correlations were demonstrated between the electrocardiographic variant differences in percentages (sigma QV2-3 and sigma QV1-6) and the radionuclear variant differences, especially the posterolateral and the infero-apical regions, as well as the posterior radionuclear index (r between 0.5 and 0.75; p less than 0.01). In addition, almost all of the patients who showed deepening of QS waves in the precordial leads also showed an increase in regional ejection fractions in uninvolved myocardium, and vice versa. It is concluded that the dynamic changes of the QS wave magnitude in the precordial leads within the evolution of acute anterior myocardial infarction well reflect the changes of the posterior noninfarcted muscle contraction and therefore offers a simple, inexpensive, and indirect electrocardiographic method for evaluating changes in contraction patterns of noninfarcted myocardium.

Electrocardiography↗

Natural course of electrocardiographic components and stages in the first twelve hours of acute myocardial infarction.

Time course evolution of R, Q, T and ST components of the electrocardiogram during the first 12 hours of an acute myocardial infarction was studied. A comparison between anterior-extensive and anteroseptal wall infarctions (anterior group), and inferior-extensive and inferior wall infarction (inferior group) showed appearance of significant Q waves within two hours in both groups. R wave loss was nearly a mirror image of Q wave development in both groups. T waves became negative and ST more isoelectric earlier in the inferior than in the anterior group. When combined variations of the four electrocardiographic components were analyzed, four stages of acute infarction were delineated. Stage I--tall R, no Q, ST elevation and positive T; Stage II--significant Q wave appearance; Stage III--negativity of T waves; and Stage IV--ST isoelectric. The inferior group reached stages III-IV within 12 hours; the anterior group remained mostly in stage II. An early appearance of Q waves correlated well with rapid progression to stages III-IV within 12 hours in both infarction groups.

Electrocardiography↗