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Abstracts

Fibrocystic Breast Disease

ABSTRACTS

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Effect of diet on excretion of estrogens in pre- and postmenopausal women.

Goldin BR, Adlercreutz H, Dwyer JT, Swenson L, Warram JH, Gorbach SL.

Cancer Res 1981 Sep;41(9 Pt 2):3771-3

Fecal, urinary, and plasma estrogens and plasma androgens were studied in healthy pre- and postmenopausal vegetarian and omnivorous women. Dietary histories of the subjects revealed that omnivores consumed a higher percentage of total protein and fat from animal sources. The total 72-hr fecal excretion as measured by dry weight was higher for vegetarians. Preliminary results indicate that vegetarian women excrete 2 to 3 times more estrogens in feces than do omnivores and that omnivores have about 50% higher mean plasma level of unconjugated estrone and estradiol than vegetarians. Estriol-3-glucuronide, a compound that is formed upon reabsorption of free estriol from the intestine, is found in lower concentrations in the urine of vegetarians. These data suggest that in vegetarians a greater amount of the biliary estrogens escape reabsorption and are excreted with the feces. The differences in estrogen metabolism may explain the lower incidence of breast cancer in vegetarian women.

Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women.

Goldin BR, Adlercreutz H, Gorbach SL, Warram JH, Dwyer JT, Swenson L, Woods MN.

N Engl J Med 1982 Dec 16;307(25):1542-7

We studied 10 vegetarian and 10 nonvegetarian premenopausal women on four occasions approximately four months apart. During each study period, the participants kept three-day dietary records, and estrogens were measured in plasma, urinary, and fecal samples. Vegetarians consumed less total fat than omnivores did (30 per cent of total calories, as compared with 40 per cent) and more dietary fiber (28 g per day, as compared with 12 g). There was a positive correlation between fecal weight and fecal excretion of estrogens in both groups (P less than 0.001), with vegetarians having higher fecal weight and increased fecal excretion of estrogens. Urinary excretion of estriol was lower in vegetarians (P less than 0.05), and their plasma levels of estrone and estradiol were negatively correlated with fecal excretion of estrogen (P = 0.005). Among the vegetarians the beta-glucuronidase activity of fecal bacteria was significantly reduced (P = 0.05). We conclude that vegetarian women have an increased fecal output, which leads to increased fecal excretion of estrogen and a decreased plasma concentration of estrogen.

Fibrocytic breast disease: current status of diagnosis and treatment.

Greenblatt RB; Vasquez J; Samaras C

Postgrad Med (UNITED STATES) Mar 1982, 71 (3) p159-63, 166-8

Improved diagnostic procedures and use of a new steroidal agent, danazol (Danocrine), should reduce the need for surgical intervention in fibrocystic breast disease. Thermography, a non-invasive procedure that may be used with impunity, may help identify women at high risk. Mammography, which is useful in revealing malignancy in an early stage, should be done in women with tow consecutive abnormal thermograms. Biopsies should be performed, however, on suspicious, firm, irregular masses, regardless of results on thermography or mammography. Use of danazol may be advantageous not only in ameliorating pain and eliminating nodosities, but also in guiding the surgeon to the nodule that is unresponsive to treatment and therefore should be evaluated by biopsy.

Extrahepatic biliary obstruction: can silymarin protect liver function?

Hagymasi K, Kocsis I, Lugasi A, Feher J, Blazovics A. 2nd Department of Internal Medicine, Semmelweiss University, Szentkiralyi u 26, H-1088 Budapest, Hungary. hkriszti@bel2.sote.hu

Phytother Res 2002 Mar;16 Suppl 1:S78-80

The hepatoprotective property of silymarin is well known. However, it is not known whether the antioxidant silymarin might have a beneficial effect in extrahepatic cholestasis in common bile duct ligated rats. Malonaldehyde property concentrations, the hydrogen-donating ability and reducing power were measured in liver homogenates by spectrophotometry, as well as free SH-group levels and glutathione-reductase activities in sera. The total scavenger capacity of the livers was quantified by a chemiluminometric method. The elevated lipid peroxidation and decreased antioxidant capacity of liver homogenates and sera could be observed in ligated rats. Silymarin pretreatment improved the antioxidant capacity of the liver, diminished the direct bilirubin concentration and caused an increase of liver enzyme activities compared with the groups without treatment. These effects of silymarin suggest that it may be a useful agent for improving the antioxidant defensive system in extrahepatic

Breast cancer.

Henderson, M., Pike, M.C., Bernstein, L., Ross, R.K.

In Cancer Epidemiology and Prevention, Second Edition 1996. Schottenfeld, D., Fraumeni, J.F., Eds. New York: Oxford University Press.

Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness.

Horner NK, Lampe JW. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

J Am Diet Assoc 2000 Nov;100(11):1368-80

Fibrocystic breast conditions, formerly referred to as fibrocystic breast disease, affect about half of all women and typically present as any combination of breast nodularity, swelling, and pain. We reviewed the literature to evaluate evidence supporting nutrition interventions commonly recommended for fibrocystic breast conditions by health care providers. Randomized, controlled studies of the effectiveness of caffeine restriction fail to support any benefit in fibrocystic breast conditions. Similarly, evidence supporting evening primrose oil, vitamin E, or pyridoxine as treatments for the discomforts of fibrocystic breast conditions is insufficient to draw conclusions about effectiveness. Dietary alterations that influence the intermediate markers for fibrocystic breast conditions include low-fat (15% to 20% energy), high-fiber (30 g/day), and soy isoflavone regimens. However, our findings provide no solid evidence for secondary prevention or treatment of fibrocystic breast conditions through a dietary approach. Health care providers should limit recommendations to proven diet therapies supported by randomized, placebo-controlled trials, given the instability inherent in fibrocystic breast conditions and the near 20% placebo effect associated with intervention. Because excessive estrogen or altered sensitivity to estrogen is the dominant theory of etiology, interventions that may modulate endogenous steroid hormones warrant further investigation as potential treatments for symptomatic fibrocystic breast conditions.

Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses' Health Study.

Huang Z, Willett WC, Colditz GA, Hunter DJ, Manson JE, Rosner B, Speizer FE, Hankinson SE. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.

Am J Epidemiol 1999 Dec 15;150(12):1316-24

This study examined prospectively the associations of waist circumference and waist:hip circumference ratio with risk of breast cancer. A total of 47,382 US registered nurses who reported their waist and hip circumferences in 1986 were followed up through May 1994 for identification of incident cases of breast cancer. During 333,097 person-years of follow-up, 1,037 invasive breast cancers were diagnosed. In proportional hazards analyses, waist circumference was nonsignificantly related to risk of premenopausal breast cancer but was significantly associated with postmenopausal breast cancer after adjustment for established breast cancer risk factors (for the highest quintile of waist circumference vs. the lowest, relative risk (RR) = 1.34; 95% confidence interval (CI): 1.05, 1.72). When the analysis was limited to postmenopausal women who had never received hormone replacement therapy, a stronger positive association was found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were further controlled for body mass index, the positive association was only slightly attenuated (RR = 1.83; 95% CI: 1.12, 2.99). Among past and current postmenopausal hormone users, no significant associations were found. Similar but slightly weaker associations were observed between waist:hip ratio and breast cancer risk. These data suggest that greater waist circumference increases risk of breast cancer, especially among postmenopausal women who are otherwise at lower risk because of never having used estrogen replacement hormones.

Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects.

Hudgins LC, Hellerstein MK, Seidman CE, Neese RA, Tremaroli JD, Hirsch J. Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA.

J Lipid Res 2000 Apr;41(4):595-604

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (4313 vs. 1213%) and obese (3715 vs. 66%) subjects, despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese. Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate. On the 10% fat diet, plasma triglycerides (fasting and 24 h) were increased and correlated with fatty acid synthesis. Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation.Thus, eucaloric, solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate, and plasma triglycerides increase in proportion to the amount of fatty acid synthesis. However, this dietary effect is not related to body mass index, insulin, or glucagon levels.

Biochemical and anthropometric characterization of morbid obesity in a large Utah pedigree.

Hunt SC, Williams RR, Adams TD. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA.

Obes Res 1995 Sep;3 Suppl 2:165S-172S

A Utah family with morbid obesity was extended to include 122 persons in four generations for the purpose of characterizing anthropometric and biochemical variables in family members with and without morbid obesity. Seventy-seven subjects had blood drawn for biochemical analyses. Of the 77 subjects, 12 were morbidly obese (> or = 44.5 kg or 100 pounds overweight), 20 were between 22.5-45.4 kg (50 and 99 pounds) overweight and 45 were less than 22.5 kg (50 pounds) overweight. Sixty-two randomly-ascertained controls were used for comparisons of age- and gender-adjusted study variables. Morbidly obese subjects had mean body mass indices (BMI) of 41.0 kg/m2 (62 kg over ideal weight) compared to 25.3 kg/m2 (10 kg overweight) in the < 22.5 kg family members (p < 0.001). The < 22.5 kg family members had lower BMI than the random controls (27.6 kg/m2, p < 0.05), indicating clear bimodality of obesity within the pedigree. Percent body fat from bioelectrical impedance was 35% versus 24% in the morbidly obese and the < 22.5 kg subjects, respectively. Idealbody weight was similar among the three pedigree weight groups. Hip and waist circumferences were much larger in the morbidly obese and the waist-to-hip ratio remained significantly greater in the morbidly obese subjects compared to the < 22.5 kg group. Morbidly obese subjects had elevated triglycerides and VLDL-C levels, low HDL-levels, and normal LDL-C levels. Fasting insulin was the best predictor of morbid obesity of all biochemical and lipid measurements (odds ratio of 4.5). Fasting insulin levels and the insulin-to-glucose ratio were more than twice as high as control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence, Screening and Management of Atypical Hyperplasia and Lobular Carcinoma In Situ 1997.

Hurley, S.F., Hart, S., Susil, B.

Canberra: National Health and Medical Research Council/National Breast Cancer Centre.

Breast health (non-cancerous breast issues).

Imaginis.

Imaginis Newsletter 2000 Nov 13.

Durham, NC: Imaginis Corporation.

Soy and breast cancer.

Imaginis.

Imaginis Newsletter 2001 Jan 20.

Durham, NC: Imaginis Corporation.

Relation between the serum level of C-peptide and risk factors for coronary heart disease and diabetic microangiopathy in patients with type-2 diabetes mellitus.

Inukai T, Matsutomo R, Tayama K, Aso Y, Takemura Y. Department of Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Japan.

Exp Clin Endocrinol Diabetes 1999;107(1):40-5

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture.

Ip MM, Masso-Welch PA, Shoemaker SF, Shea-Eaton WK, Ip C. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA. mip@sc3101.med.buffalo.edu

Exp Cell Res 1999 Jul 10;250(1):22-34

The trace fatty acid conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis when fed prior to carcinogen during pubertal mammary gland development or during the promotion phase of carcinogenesis. The following studies were done to investigate possible mechanisms of these effects. Using a physiological model for growth and differentiation of normal rat mammary epithelial cell organoids (MEO) in primary culture, we found that CLA, but not linoleic acid (LA), inhibited growth of MEO and that this growth inhibition was mediated both by a reduction in DNA synthesis and a stimulation of apoptosis. The effects of CLA did not appear to be mediated by changes in epithelial protein kinase C (PKC) since neither total activity nor expression nor localization of PKC isoenzymes alpha, betaII, delta, varepsilon, eta, or zeta were altered in the epithelium of CLA-fed rats. In contrast, PKCs delta, varepsilon, and eta were specifically upregulated and associated with a lipid-like, but acetone-insoluble, fibrillar material found exclusively in adipocytes from CLA-fed rats. Taken together, these observations demonstrate that CLA can act directly to inhibit growth and induce apoptosis of normal MEO and may thus prevent breast cancer by its ability to reduce mammary epithelial density and to inhibit the outgrowth of initiated MEO. Moreover, the changes in mammary adipocyte PKC expression and lipid composition suggest that the adipose stroma may play an important in vivo role in mediating the ability of CLA to inhibit mammary carcinogenesis. Copyright 1999 Academic Press.

Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats.

Ip C, Banni S, Angioni E, Carta G, McGinley J, Thompson HJ, Barbano D, Bauman D. Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

J Nutr 1999 Dec;129(12):2135-42

Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product.

Stereotactic histologic biopsy in breasts with implants.

Jackman RJ, Lamm RL. Department of Radiology, Palo Alto Medical Clinic, 795 El Camino Real, Palo Alto, CA 94301. From the 1999 RSNA scientific assembly. Received January 4, 2001.

Radiology 2002 Jan;222(1):157-64

PURPOSE: To describe our experience with stereotactic histologic biopsy in patients with breast implants. MATERIALS AND METHODS: Thirty-one (1.3%) of 2,399 consecutive lesions on which stereotactic histologic biopsy was performed were in breasts containing implants. Biopsy difficulties were evaluated for lesions in breasts with and breasts without implants. Biopsy was performed on lesions in patients with implants prone on a dedicated table, with automated large-core (n = 13) or directional vacuum-assisted (n = 18) devices. Follow-up was surgical (11 of 11 malignancies and two of three high-risk lesions) and mammographic (one of three high-risk lesions and 17 of 17 benign lesions). RESULTS: There were no implant ruptures, hematomas requiring drainage, infections requiring treatment, false-negative findings, or histologic underestimations. Difficulties with stereotactic histologic biopsy were more prevalent in breasts with implants and included positioning problems in 10 (50%) of 20 lesions in breasts with subglandular implants and zero (0%) of 10 with subpectoral implants, lesions seen on only one view in four (13%) of 31 lesions, specimen radiographs negative for calcifications in two (10%) of 20 lesions, prominent bleeding in two (6%) of 31 lesions, and suboptimally small tissue samples in three (10%) of 31 lesions. CONCLUSION: Stereotactic histologic biopsy is safe in breasts with implants. Compared with that in breasts without implants, biopsy is often technically more difficult and may eventually prove less accurate.

Fish consumption and breast cancer risk: an ecological study.

Kaizer L, Boyd NF, Kriukov V, Tritchler D. Ludwig Institute for Cancer Research (Toronto Branch), Ontario, Canada.

Nutr Cancer 1989;12(1):61-8

There is experimental evidence that fish oils protect against mammary carcinogens in animals. However, there has been little investigation of the possible relevance of this finding to breast cancer in humans. We compared breast cancer incidence and mortality rates with estimates of the consumption of fish and other foods and nutrients in the countries for which reliable data are available. The results showed an inverse association between percent calories from fish and breast cancer rates that was consistent with a protective effect. This analysis confirmed the finding of others that dietary fat is strongly associated with international variation in breast cancer rates. It also showed that of the dietary components considered, percent calories from fish was the factor most strongly correlated with breast cancer rates after statistical adjustment for dietary fat intake. This result is therefore in accord with animal experimental data and suggests that the omega-3 fatty acids contained in certain fish may protect against breast cancer.

The deadly quartet. Upper-body obesity, glucose intolerance, hpertriglyceridemia, and hypertension.

Kaplan NM. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9030.

Arch Intern Med 1989 Jul;149(7):1514-20

The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, and hypertriglyceridemia even in the absence of significant overall obesity. This article examines the evidence that upper-body obesity, as usually induced by caloric excess in the presence of androgens, mediates these problems by way of hyperinsulinemia. Because of these interrelationships, there is a need to identify and prevent upper-body obesity or, failing that, to provide therapies that will control the associated problems without aggravating hyperinsulinemia.

Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats.

Kimura M, Tanaka S, Yamada Y, Kiuchi Y, Yamakawa T, Sekihara H. The Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.

Endocrinology 1998 Jul;139(7):3249-53

Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant circulating adrenal steroids in humans. Administration of DHEA has been reported to have beneficial effects on obesity, hyperlipidemia, diabetes, and atherosclerosis in obese rodents, although its effects on insulin resistance have not been fully elucidated. In this study, the effects of DHEA treatment on insulin sensitivity were investigated in genetically obese Zucker rats, an animal model of insulin resistance, using the euglycemic clamp technique. After 0.4% DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body weight and plasma insulin decreased and glucose disposal rate (GDR), which was normally reduced in obese rats, rose significantly compared with age-and sex-matched control obese rats. On the other hand, although the pair-fed obese rats also showed levels of weight reduction similar to those of DHEA-treated rats, the increase in GDR of DHEA-treated rats was significantly greater than in pair-fed rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of obese rats. Serum concentration of tumor necrosis factor (TNF)-alpha, one of cytokines causing insulin resistance, was also reduced significantly in DHEA-treated, but not in pair-fed obese rats. In conclusion, our results suggest that DHEA treatment reduces body weight and serum TNF-alpha independently, and that both may ameliorate insulin resistance in obese Zucker fatty rats.

Antioxidant properties of silybin glycosides.

Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichova J, Walterova D. Centre for Bioanalytical Research, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic.

Phytother Res 2002 Mar;16 Suppl 1:S33-9

New soluble derivatives of the hepatoprotective flavonolignan silybin (1), namely silybin galactoside (2), glucoside (3), lactoside (4) and maltoside (5) were investigated for their radical scavenging and antilipoperoxidation properties. According to cyclic voltammetry the results show that glycosides are weaker electron donors than silybin, although it was of interest that they were found to be more potent scavengers of the 1,1-diphenyl-2-picrylhydrazyl and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-derived radicals. The glycosides (2)-(5) were more efficient than silybin in preventing tert-butylhydroperoxide-induced lipoperoxidation of rat liver mitochondrial membranes. Furthermore, glycosides (2)-(5) were significantly more cytoprotective than silybin in tert-butylhydroperoxide-damaged rat erythrocytes and primary hepatocyte cultures. Glycosylation of silybin substantially reduced its toxic effects in primary cultured hepatocytes observed during prolonged incubation. These results suggest that silybin glycosides are suitable soluble derivatives of silybin for experimental studies and may have therapeutic potential. Copyright 2002 John Wiley & Sons, Ltd.

Prolactin response to thyrotropin-releasing hormone stimulation and dopaminergic inhibition in benign breast disease.

Kumar S, Mansel RE, Hughes LE, Woodhead JS, Edwards CA, Scanlon MF, Newcombe RG.

Cancer 1984 Mar 15;53(6):1311-5

Pituitary function was tested in predefined clinical groups of benign breast disease under strictly controlled clinical and laboratory conditions. Two different tests of prolactin storage and control mechanisms, direct stimulation by thyrotropin-releasing hormone (TRH) and inhibition of dopaminergic control by domperidone, indicate a significant abnormality in patients with severe cyclical mastalgia and nodular breast disease (P less than 0.05 and P less than 0.002), but not in those with noncyclical mastalgia. No abnormalities of thyroid function were found.

Prediction of response to endocrine therapy in pronounced cyclical mastalgia using dynamic tests of prolactin release.

Kumar S, Mansel RE, Hughes LE, Edwards CA, Scanlon MF.

Clin Endocrinol (Oxf) 1985 Dec;23(6):699-704

Many of the endocrine agents currently used to treat symptomatic benign breast disease modify the action or secretion of prolactin. We have compared the responses to hormonal therapy with dynamic assessment of prolactin control in 29 patients with cyclical mastalgia and in 7 patients with non-cyclical mastalgia. The tests of prolactin release used were direct stimulation by TRH or dopaminergic blockade by domperidone. These were carried out before treatment in the mastalgic patients and also in 22 age-matched asymptomatic controls. The response to treatment was assessed using a special pain chart and visual linear analogue scale. Patients with cyclical mastalgia could be divided into two groups: those in whom the peak prolactin release was exaggerated (greater than 4000 mU/l) and those in whom the prolactin release was less marked and similar to control subjects and patients with non-cyclical mastalgia. Patients in the cyclical mastalgia group with a high peak prolactin release responded to hormonal treatment significantly more frequently (90%) than those with a normal prolactin release (50%). Basal prolactin levels did not correlate with the response to treatment. In the non-cyclical mastalgia group, no patient had peak prolactin release greater than 4000 mU/l and none responded to therapy. This study indicates that dynamic tests of prolactin release in cyclical mastalgia may be useful in predicting the subsequent satisfactory response to endocrine therapy if a high peak prolactin release is induced.

The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial.

Kurzman ID, Panciera DL, Miller JB, MacEwen EG. Department of Medical Sciences, University of Wisconsin, School of Veterinary Medicine, Madison 53706, USA.

Obes Res 1998 Jan;6(1):20-8

Dehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.

The Woman's Health Companion 1996.

Lark, S.M.

Berkeley, CA: Celestial Arts.

Benign breast disease and consumption of beverages containing methylxanthines.

La Vecchia C, Franceschi S, Parazzini F, Regallo M, Decarli A, Gallus G, Di Pietro S, Tognoni G.

Natl Cancer Inst 1985 May;74(5):995-1000

The relationship between methylxanthine (Mx) consumption and benign breast disease was evaluated in a case-control study of 288 women with histologically confirmed benign breast lumps (203 dysplastic lesions and 85 benign tumors) and 2 groups of control women--285 patients in the hospital for acute conditions apparently unrelated to the consumption of Mx-containing beverages and 291 outpatients. The relative risk estimates of dysplastic breast lesions (fibrocystic disease), with allowance for all identified potential distorting factors, for women who drank 1-2 or 3 or more cups of coffee per day were 4.1 and 6.4, respectively, when the hospital controls were the comparison group and 2.0 and 3.7, respectively, when the outpatient controls were the comparison group. The relationship was even stronger when the total consumption of Mx-containing beverages (coffee plus tea) was considered and increased with increasing duration of use. The association was not explained by any of the major risk factors for fibrocystic breast diseases or by differences in general characteristics or other lifestyle habits between cases and controls. Mx consumption was not related to the risk of benign breast tumors (fibroadenomas). These findings support the hypothesis that Mx consumption is related to the risk of dysplastic lesions of the breast.

Cholesterol and bile acid metabolism in obesity.

Leijd B.

Clin Sci (Lond). 1980 Sep;59(3):203-6.

1. The present study was undertaken to determine the influence of obesity on bile acid kinetics and cholesterol balance in man. 2. Fourteen obese and normolipidaemic patients (160 +/- 6% of ideal body weight, mean +/- SEM) were studied under standardized dietary conditions. Bile acid kinetics, were determined with the aid of 14C-labelled cholic acid and chenodeoxycholic acid. Cholesterol balance was calculated as the sum of bile acid synthesis plus daily faecal excretion of neutral C27 steroids minus dietary intake of cholesterol. The results obtained were compared with previously published data on control subjects (n = 13). 3. The cholesterol balance was higher in the obese patients (2.61 +/- 0.27 mmol/day) than in the control subjects (1.78 +/- 0.22 mmol/day), owing to a higher excretion of neutral steroids. When expressed per kg of body weight the cholesterol balance was quite normal in the obese patients.

[Hormonal contraception and benign breast disease. Evaluation of a treatment protocol for chronic mastopathy with mastalgia] [Article in Italian]

Leonardi M. Divisione di Ginecologia e Ostetricia, Azienda USSL Ambito Territoriale N. 14, Presidio Ospedaliero di Iseo (Brescia).

Minerva Ginecol 1997 Jun;49(6):271-6

INTRODUCTION AND AIMS: The aim of this study was to study patients suffering from mammary nodules, fibrocystic disease and mastodynia. Having established the absence of malignant disease, the effect of EP (oestroprogestin) was evaluated in the treatment of fibrocystic disease with mastalgia.

METHODS: From January 1990 to December 1995 a total of 1921 women underwent breast examination at the "Centro di Fisiopatologia della Mammella" in the Division of Gynecology and Obstetrics of Iseo Municipal Hospital. Subjects were aged between 9 and 84 years old. The experimental protocol included a retrospective study of a group of 89 patients suffering from chronic fibrocystic disease with mastalgia with a 3-month follow-up. The clinical examination was commenced by recording the patient's history and the measurement of the thickness of the gland and the evaluation of mastalgia represented important stages of the eco-clinical assessment. The setting for the study was the breast pathology out-patient clinic of the Division of Gynecology and Obstetrics. These women regularly attended our outpatient clinics for the following reasons: depistage, mastodynia, mammary secretion, self-diagnosis of mammary nodules, checkups in patients during follow-up after surgery for genital neoplasia. All patients underwent clinical, echographic and often mammography/X-ray. Patients were selected on the basis of the following criteria: absence of malignant pathology and presence of chronic fibrocystic disease with mastalgia. Of those admitted to the study (no. = 89), only 59 completed the course. In addition to the absence of malignant pathology and the presence of chronic fibrocystic disease with mastalgia, the following parameters were assessed: measurement of the thickness of the mammary gland involving QSE before and after 3-month treatment with EP. The EP used were: gestodene 0.075 mg and etynylestradiol 0.03 mg-Minulet, or etynylestradiol 0.02 mg and dexogestrel 0.150 mg-Securgin and Mercilon.

RESULTS: The response to treatment was classified according to the 4 levels of the Cardiff Breast Score (CBS). The results were relatively good: 35.59% of patients showed a reduction in symptoms; 25.42% showed a marked improvement, and 18.64% a remission of symptoms. No effect was reported in 20.33% of patients.

CONCLUSIONS: In conclusion, it may be said that EP treatment for 3 months can at least be proposed in patients with chronic fibrocystic disease and mastalgia given that a reduction and improvement in symptoms was seen in 60% of patients.

DHEA(S): the fountain of youth.

Leowattana W. Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

J Med Assoc Thai 2001 Oct;84 Suppl 2:S605-12

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are weak androgens produced primarily by the adrenal gland. Although their plasma concentrations by far exceed those of any other adrenal product, their physiological roles have not yet been determined. In plasma, where the major portion of these hormones is present in the sulfate form, it is possible that DHEAS serves as a reservoir for DHEA. Since various tissues have been shown to contain steroid sulfatases. The peak plasma levels of DHEA and DHEAS occur at approximately age 25 years, decrease progressively thereafter, and diminish by 95 per cent around the age of 85 years. The decline of DHEAS concentrations with aging has led to the suggestion that DHEAS could play a role in itself and be implicated in longevity. Moreover, the epidemiological evidence has shown that adult men with high plasma DHEAS levels are less likely to die of cardiovascular disease. DHEA has also been shown to increase the body's ability to transform food into energy and burn off excess fat. Another recent finding involves the anti-inflammatory properties of DHEA. It has been known that DHEA can lower the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). It should be pointed out that chronic inflammation is known to play a critical role in the development of the killer diseases of aging: heart disease, Alzheimer's disease and certain types of cancer. In conclusion, DHEA or DHEAS administration combined with conventional treatment may be implicated in particular conditions to improve the quality of life.

The effect of vitamin E on mammary dysplasia: a double-blind study.

London RS, Sundaram GS, Murphy L, Manimekalai S, Reynolds M, Goldstein PJ.

Obstet Gynecol 1985 Jan;65(1):104-6

Alpha-tocopherol (vitamin E) has been used to treat patients with benign breast disease. To evaluate the efficacy of this treatment, a randomized, double-blind placebo-controlled study was performed on 128 women with confirmed mammary dysplasia. Patients were treated with placebo or 150, 300, or 600 IU of d, 1 alpha-tocopherol per day for two months; breast examinations, sonography, and thermography were performed in the midluteal phase of the menstrual cycle before and after treatment. No significant objective effects to treatment were noted in any of the parameters monitored. In addition, serum concentrations of estradiol, progesterone, dehydroepiandrosterone sulfate, and testosterone were measured before and after treatment. There were no significant effects on concentrations of these hormones. From this study, d, 1 alpha-tocopherol does not seem to be beneficial in the treatment of patients with mammary dysplasia.

Endocrine parameters and alpha-tocopherol therapy of patients with mammary dysplasia.

London RS, Sundaram GS, Schultz M, Nair PP, Goldstein PJ.

Cancer Res 1981 Sep;41(9 Pt 2):3811-3

Patients with mammary dysplasia (17 patients) and controls (6 patients) were treated in a double-blind study with alpha-tocopherol acetate (600 units/day). Determination of serum alpha-tocopherol, estradiol, estriol., and progesterone were made from blood samples collected on Day 21 of the menstrual cycle before and during therapy. Eight-eight % of patients showed clinical response to therapy. Serum alpha-tocopherol concentrations rose after therapy in patients and controls. Serum estradiol and progesterone concentration were not statistically different in patients or controls after therapy, although patients showed a trend toward increased serum progesterone concentration. However, the ratio of progesterone to estradiol, which is abnormal in mammary dysplasia patients, rose from 30 +/- 7 (S.E.) to 53 +/- 11 in patients after alpha-tocopherol therapy (p less than 0.05). Control patients showed no significant change in progesterone/estradiol ratio. Results of this study indicate that alpha-tocopherol therapy may correct an abnormal progesterone/estradiol ratio in patients with mammary dysplasia, with implications on reducing future risk for malignant breast disease.

Treatment of breast fibrocystic disease with tanazol

Lopez S.P.; Martinez E.J.; Reillo M. M. Reillo, Servicio Obstetricia y Ginecologia, Hospital Marina Baixa, Villajoyosa, Alicante Spain

Acta Ginecologica (ACTA GINECOL.) (Spain) 1996, 53/10 (304-309)

Purpose: To assess the response of breast fibrocystic disease treated with tanazol or gestagens. Design: Retrospective and comparative study on therapy with tanazol or gestagens. Material and methods: Clinic, echographic, and mammografic features of breast fibrocystic disease were analyzed in 119 women. These patients were treated with tanazol or gestagens over 6 months at least. Conclusions: Tanazol gets complete improvement of symptoms in 25.2% of cases; partial improvement in 10.9%, and no improvement in 8.4% of them versus progestagens in 33.6%, 8.4% and 17.7% respectively. These outcomes were remarkable in patients with multiple palpable nodes of the breast. There were significant differences (p = 0.023) in these patients but no in patients with breast pain.

[Treatment of fibrocystic breast disease with lisuride] [Article in Spanish]

Lopez Rosales C, Romero Espinosa RE, Juarez Vazquez J. Hospital Dr. Dario Fernandez Fierro, ISSSTE, Mexico, D.F.

Ginecol Obstet Mex 1991 Dec;59:358-61

To study the efficacy of lisuride in fibrocystic mastopathy, we conducted a clinical trial in 23 out patients, aged 19-50 years, randomly recruited from the gynecological service of the ISSSTE, Dr. Dario Fernandez Fierro. Hospital. The only exclusion criteria was having received previous treatment. The patients clinical history was recorded. Physical examination, hormone profile (FSH, LH, prolactin, testosterone, estrogen and progesterone) and ultrasound exam of the mammae at baseline were performed in all patients, as well as, mammography in patients older than 40 years or those requiring so. Treatment was started with 1/2 tablet of lisuride (0.1 mg)/8 hours, preferably with meals, for 3 months. At the end of therapy, hormone profile, ultrasound of the mammae and physical examination were repeated for control purposes. We obtained the following results; fibrocystic mastopathy was most frequent in women aged 20-29 years, mean age 31 years symptoms disappeared in 36.9% and were reduced notably in 63.1%, of cases. Grade O ultrasound lesions disappeared in 100% of patients and grade I and II lesions improved. On physical examination all patients showed improvement; estrogen values were reduced and progesterone incremented. The prolactin level were normal at baseline, as well as by the end of treatment. One patient suffered severe side effects which required interruption of treatment; 4 patients experimenting light side effects were able to continue therapy and in the remaining 18 patients, no adverse reactions were observed.

Mammographic breast density during hormone replacement therapy: effects of continuous combination, unopposed transdermal and low-potency estrogen regimens.

Lundstrom E, Wilczek B, von Palffy Z, Soderqvist G, von Schoultz B. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.

Climacteric 2001 Mar;4(1):42-8

OBJECTIVE: The aim of this study was to evaluate the impact of different hormone replacement therapy (HRT) regimens on mammographic breast density.

STUDY DESIGN: Mammographic density was recorded in women participating in a population-based screening program. At first mammogram, all women were non-users of HRT, and thereafter reported continuous use of the same HRT regimen. The study population comprised 158 women: a total of 52 women were using continuous combined HRT (conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 5 mg); 51 women were using low-dose oral estrogen alone (estriol 2 mg daily); and 55 women were using unopposed transdermal estrogen given as a patch (estradiol 50 micrograms/24 h). Films were coded and analyzed for mammographic density by an independent radiologist blinded to treatments. Mammographic density was classified according to Wolfe.

RESULTS: An increase in mammographic density was much more common among women taking continuous combined HRT (40%) than for those using oral low-dose estrogen (6%) and transdermal (2%) treatment. The increase in density was already apparent at the first visit after starting HRT. During long-term follow-up, there was very little change in mammographic status.

CONCLUSION: HRT regimens were shown to have different effects on the normal breast. There is an urgent need to clarify the biological nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk.

Upgrade rate of core biopsy-determined atypical ductal hyperplasia by open excisional biopsy.

Maganini RO, Klem DA, Huston BJ, Bruner ES, Jacobs HK. The Breast Health Center, DuPage Medical Group, 1250 N. Mill St., Naperville, IL 60563, USA.

Am J Surg 2001 Oct;182(4):355-8

BACKGROUND: Core biopsy finding of atypical ductal hyperplasia (ADH) are generally followed by open biopsy to avoid underestimation of malignant disease.

METHODS: Retrospective examination of 11 gauge stereotactic-guided vacuum-assisted core biopsies was made with respect to ADH diagnosis, follow-up open biopsy, and upgrade rate. Readily available clinical, mammographic, and pathologic features potentially contributory to an upgrade were studied.

RESULTS: This series of 1,313 patients had 43 ADH diagnoses. Thirty-two had open follow-up. There were 4 upgrades. Mammographic indication for biopsy, age, removal of calcifications, and the percentage of ADH in the specimen were not significant in predicting an upgrade with all probabilities over 0.10, odds ratios not different than 1, and 95% bounds all encompassing 1.

CONCLUSIONS: These data indicate a high upgrade rate (13%) for ADH-positive core biopsies with no definitive predictive criteria for an upgrade. Our data support follow-up excision of ADH lesions diagnosed by core biopsy.

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France.

Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonniere F, Body G, Le Floch O, Chajes V. Laboratoire de Biologie des Tumeurs, Clinique d'Oncologie-Radiotherapie, Service de Gynecologie-Obstetrique, E.A. 2103, Unite de Recherche Associee Universite-INRA, CHU, Tours, France.

Int J Cancer 2002 Mar 1;98(1):78-83

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer. Copyright 2001 Wiley-Liss, Inc.

Effect of herbal teas on hepatic drug metabolizing enzymes in rats.

Maliakal PP, Wanwimolruk S. School of Pharmacy, University of Otago, Dunedin, New Zealand.

J Pharm Pharmacol 2001 Oct;53(10):1323-9

We have investigated the effect of herbal teas (peppermint, chamomile and dandelion) on the activity of hepatic phase I and phase II metabolizing enzymes using rat liver microsomes. Female Wistar rats were divided into six groups (n = 5 each). Three groups had free access to a tea solution (2%) while the control group had water. Two groups received either green tea extract (0.1%) or aqueous caffeine solution (0.0625%). After four weeks of pretreatment, different cytochrome P450 (CYP) isoforms and phase II enzyme activities were determined by incubation of liver microsomes or cytosol with appropriate substrates. Activity of CYP1A2 in the liver microsomes of rats receiving dandelion, peppermint or chamomile tea was significantly decreased (P < 0.05) to 15%, 24% and 39% of the control value, respectively. CYP1A2 activity was significantly increased by pretreatment with caffeine solution. No alterations were observed in the activities of CYP2D and CYP3A in any group of the pretreated rats. Activity of CYP2E in rats receiving dandelion or peppermint tea was significantly lower than in the control group, 48% and 60% of the control, respectively. There was a dramatic increase (244% of control) in the activity of phase II detoxifying enzyme UDP-glucuronosyl transferase in the dandelion tea-pretreated group. There was no change in the activity of glutathione-S-transferase. The results suggested that, like green and black teas, certain herbal teas can cause modulation of phase I and phase II drug metabolizing enzymes.

Effects of eicosapentaenoic and gamma-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats.

Mancuso P, Whelan J, DeMichele SJ, Snider CC, Guszcza JA, Claycombe KJ, Smith GT, Gregory TJ, Karlstad MD. Life Sciences Program in Physiology, University of Tennessee, USA.

Crit Care Med 1997 Mar;25(3):523-32

OBJECTIVES: Proinflammatory eicosanoids (cyclooxgenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and gamma-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n-6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition.

DESIGN: Prospective, randomized, controlled, double-blind study.

SETTING: Research laboratory at a university medical center.

SUBJECTS: Male Long-Evans rats, weighing 250 g.

INTERVENTIONS: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F1 alpha were measured in a third group of prefed rats.

MEASUREMENT AND MAIN RESULTS: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187-stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenic acid were higher, with 20% fish oil, and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil.

CONCLUSIONS: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids.

Effects and tolerability of n-6 essential fatty acid supplementation in patients with recurrent breast cysts.

Mansel, R.E., Gateley, C.A., Harrison, B.J. et al.

J. Nutr. Med. 1990a; 1: 195-200.

No abstract available.

A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts.

Mansel RE, Harrison BJ, Melhuish J, Sheridan W, Pye JK, Pritchard G, Maddox PR, Webster DJ, Hughes LE. University Department of Surgery, Cardiff, Wales, United Kingdom.

Ann N Y Acad Sci 1990;586:288-94

Two hundred women with breast cysts proven by aspiration were entered into a randomized double-blind trial of Efamol (evening primrose oil) at a dose of 6 capsules daily or equivalent placebo dose for a year. Cysts were categorized by initial electrolyte composition, and follow-up continued for 1 year posttherapy. Recurrent cyst formation in the first year was slightly (but not significantly) lower in the Efamol group compared with the placebo-treated group. The Efamol treatment was well tolerated as the dropout rate was only 7% and equal in both the active and placebo groups. The initial electrolyte composition did not predict for cyst recurrence.

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