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Biomedical subjects

L Plouffe

Publications and source records attributed to L Plouffe.

At least 19 recordsLinked to original sources

Comparative health effects of margarines fortified with plant sterols and stanols on a rat model for hemorrhagic stroke.

There is increased acceptance of fortifying habitual foods with plant sterols and their saturated derivatives, stanols, at levels that are considered safe. These sterols and stanols are recognized as potentially effective dietary components for lowering plasma total and LDL cholesterol. Our previous studies have shown that daily consumption of plant sterols promotes strokes and shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats. These studies question the safety of plant sterol additives. The present study was performed to determine whether a large intake of plant stanols would cause nutritional effects similar to those seen with plant sterols in SHRSP rats. Young SHRSP rats (aged 26-29 d) were fed semipurified diets containing commercial margarines fortified with either plant stanols (1.1 g/100 g diet) or plant sterols (1.4 g/100 g diet). A reference group of SHRSP rats was fed a soybean oil diet (0.02 g plant sterols/100 g diet and no plant stanols). Compared to soybean oil, both plant stanol and plant sterol margarines significantly (P < 0.05) reduced the life span of SHRSP rats. At the initial stages of feeding, there was no difference in the survival rates between the two margarine groups, but after approximately 50 d of feeding, the plant stanol group had a slightly, but significantly (P < 0.05), lower survival rate. Blood and tissue (plasma, red blood cells, liver, and kidney) concentrations of plant sterols in the plant sterol margarine group were three to four times higher than the corresponding tissue concentrations of plant stanols in the plant stanol group. The deformability of red blood cells and the platelet count of SHRSP rats fed the plant sterol margarine were significantly (P < 0.05) lower than those of the plant stanol margarine and soybean oil groups at the end of the study. These parameters did not differ between the soybean oil and plant stanol margarine groups. These results suggest that, at the levels tested in the present study, plant stanols provoke hemorrhagic stroke in SHRSP rats to a slightly greater extent than plant sterols. The results also suggest that the mechanism by which plant stanols shorten the life span of SHRSP rats might differ from that of plant sterols.

Animals↗

Effect of raloxifene on sexual function in postmenopausal women.

OBJECTIVE: To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream. METHODS: A total of 187 naturally postmenopausal women, 42-80 years of age, with signs of genitourinary atrophy were enrolled in this 6-month, multicenter, parallel-group study. Subjects were randomized to oral raloxifene HCl 60 mg daily or matching placebo; the same subjects were also randomized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months, followed by conjugated estrogen cream for 3 months. Both investigators and subjects were masked to the identity of the oral medication. The vaginal preparations were administered in an open-label fashion. The Sexual Activity Questionnaire (SAQ) was administered at baseline and at 3 and 6 months. Safety was assessed throughout the study. RESULTS: A total of 102 women were sexually active at baseline and, of these, 82 were also sexually active at the 6-month end-point. At 6 months, raloxifene and placebo, in the presence of vaginal conjugated estrogen cream, were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity. There were no significant differences between raloxifene and placebo groups in any SAQ item. Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo. No difference in adverse events was observed between groups. CONCLUSION: Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream.

Administration, Intravaginal↗

Raloxifene effect on frequency of surgery for pelvic floor relaxation.

OBJECTIVE: To assess the effects of raloxifene therapy on the frequency of surgery for pelvic floor relaxation in postmenopausal women. METHODS: This analysis used safety data through 3 years of treatment from three double-masked, placebo-controlled, randomized trials of raloxifene, which included 6926 postmenopausal women with uteri at entry. Studies 1 and 2 enrolled 969 nonosteoporotic, postmenopausal women who were assigned to 30, 60, or 150 mg per day raloxifene or placebo. Study 3 enrolled 5957 osteoporotic, postmenopausal women randomized to raloxifene 60 or 120 mg per day or placebo. Indications for any reported pelvic operations were identified, including procedures performed for pelvic organ prolapse or urinary incontinence. RESULTS: A total of 34 (1.51%) women in the placebo group and 35 (0.75%) raloxifene-treated women underwent surgical procedures for pelvic floor relaxation. The odds ratio (and 95% confidence interval) for pelvic floor repair in women assigned to raloxifene was 0.50 (0.31, 0.81). Thus, raloxifene therapy was associated with a significantly reduced risk for pelvic floor surgery (P <.005). CONCLUSION: Raloxifene does not increase pelvic floor relaxation. An apparent protective effect on pelvic floor function warrants further investigation.

Aged↗

The effect of selective estrogen receptor modulators on parameters of the hypothalamic-pituitary-gonadal axis.

The SERMs currently in clinical practice or in late stages of clinical development have been studied primarily for their effects on the breast, cardiovascular, bone, and reproductive systems. The effect of SERMs on the hypothalamic-pituitary-gonadal (HPG) axis has not been the primary focus of the studies conducted thus far. However the effect of SERMs on the HPG axis and the associated regulation of endocrine parameters may play an important role in their overall clinical profile. In this review the effects of selected SERMs on the HPG axis in premenopausal women, postmenopausal women, and men are summarized.

Female↗

Influence of sources of dietary oils on the life span of stroke-prone spontaneously hypertensive rats.

In recent studies, the life span of stroke-prone spontaneously hypertensive (SHRSP) rats was altered by a variety of dietary fats. It was relatively shorter in rats fed canola oil as the sole source of fat. The present study was performed to find out whether the fatty acid profile and the high content of sulfur compounds in canola oil could modulate the life span of SHRSP rats. SHRSP rats (47 d old, n = 23/group) were matched by body weight and systolic blood pressure and fed semipurified diets containing 10% canola oil, high-palmitic canola oil, low-sulfur canola oil, soybean oil, high-oleic safflower oil, a fat blend that mimicked the fatty acid composition of canola oil, or a fat blend high in saturated fatty acids. A 1% sodium chloride solution was used as drinking water to induce hypertension. After consuming the diets for 37 d, five rats from each dietary group were killed for collection of blood and tissue samples for biochemical analysis. The 18 remaining animals from each group were used for determining their life span. The mean survival time of SHRSP rats fed canola oil (87.4+/-4.0 d) was not significantly different (P > 0.05) from those fed low-sulfur canola oil (89.7+/-8.5 d), suggesting that content of sulfur in canola oil has no effect on the life span of SHRSP rats. The SHRSP rats fed the noncanola oil-based diets lived longer (mean survival time difference was 6-13 d, P < 0.05) than those fed canola and low-sulfur canola oils. No marked differences in the survival times were observed among the noncanola oil-based groups. The fatty acid composition of the dietary oils and of red blood cells and liver of SHRSP rats killed after 37 d of treatment showed no relationship with the survival times. These results suggest that the fatty acid profile of vegetable oils plays no important role on the life span of SHRSP rat. However, phytosterols in the dietary oils and in liver and brain were inversely correlated with the mean survival times,indicating that the differential effects of vegetable oils might be ascribed, at least partly, to their different phytosterol contents.

Animals↗

Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60.

OBJECTIVE: To assess the uterine effects of 3 years of therapy with raloxifene in healthy, postmenopausal women under age 60. METHODS: Integrated data from two identically designed, randomized, double-masked, placebo-controlled clinical trials were analyzed. Nine hundred sixty-nine healthy women with uteri (ages 45 through 60, 2 to 8 years postmenopausal) were assigned randomly to raloxifene 30, 60, or 150 mg per day, or an identical placebo for 3 years. Endometrial thickness was evaluated with transvaginal ultrasonography every 6 months for 2 years and again after 3 years. Further uterine evaluation, including endometrial sampling if necessary, was initiated for vaginal bleeding or findings of endometrial thickness greater than 5 mm. RESULTS: Endometrial thickness was unchanged by raloxifene and not significantly different from placebo at any time. One hundred seventy-two women had at least one episode of endometrial thickness greater than 5 mm or vaginal bleeding distributed equally among all groups. A total of 102 (10.5%) women underwent endometrial sampling at least once: 15 (1.5%) for vaginal bleeding, 78 (8.0%) for endometrial thickness greater than 5 mm, and nine (0.9%) for other reasons. There were no significant treatment differences in the proportion of women sampled, in the clinical findings, or in the histologic diagnoses. CONCLUSION: Raloxifene given to healthy postmenopausal women at doses from 30 to 150 mg per day does not stimulate uterine growth and does not cause vaginal bleeding, spotting, or discharge through 3 years of therapy. Thus, any bleeding during therapy should be deemed unexpected and prompt a clinical evaluation.

Endometrium↗

Disorders of excessive hair growth in the adolescent.

Virilization is most often the reflection of a serious underlying condition. Diagnosis and management should be prompt, thorough, and comprehensive. Hirsutism is the manifestation of a variety of disorders. It may be associated with serious acute medical conditions, chronic disorders, or idiopathic. The diagnosis should be methodical and adjusted to the nature of the clinical presentation. Several therapeutic modalities are effective and produce satisfactory results for most patients.

Adolescent↗

Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats.

Previous studies have shown that canola oil (CA), compared with soybean oil (SO), shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats, a widely used model for hemorrhagic stroke. SHRSP rats are highly sensitive to dietary cholesterol manipulations because a deficiency of membrane cholesterol makes their cell membranes weak and fragile. Phytosterols, abundant in CA but not in SO, can inhibit the absorption of cholesterol and also replace a part of cholesterol in cell membranes. This study was performed to determine whether the high concentration of phytosterols in CA might account for its life-shortening effect on SHRSP rats. Male, 35-d-old SHRSP rats (n = 28/group) were fed semipurified diets containing CA, SO, CA fortified with phytosterols (canola oil + phytosterols, CA + P), SO fortified with phytosterols (soybean oil + phytosterols, SO + P), corn oil (CO), olive oil (OO) or a fat blend that mimicked the fat composition of a representative Canadian diet (Canadian fat mimic, CFM; 10 g/100 g diet). These fats provided 97, 36, 207, 201, 114, 27 and 27 mg phytosterols/100 g diet, respectively. Ten rats from each group were killed after 30-32 d for blood and tissue analyses. The remaining rats (18/group) were used for determination of life span. The life span of SHRSP rats fed the high phytosterol oils (CA, CA + P, SO + P and CO) was significantly (P<0.05) shorter than that of CFM- and SO-fed rats. At 30-32 d, the groups fed the high phytosterol oils had greater levels of phytosterols and significantly (P<0.05) higher ratios of phytosterols/cholesterol in plasma, RBC, liver and kidney, and a significantly (P<0.05) lower RBC membrane deformabilty index than the groups fed oils low in phytosterols (SO, OO and CFM). The mean survival times were correlated with RBC deformability index (r(2) = 0.91, P = 0.0033) and cholesterol concentration (r(2) = 0.94, P = 0.0016), and inversely correlated with RBC phytosterol concentration (r(2) = 0.58, P = 0.0798) and phytosterols/cholesterol (r(2) = 0.65, P = 0.0579), except in the OO group. This study suggests that the high concentration of phytosterols in CA and the addition of phytosterols to other fats make the cell membrane more rigid, which might be a factor contributing to the shortened life span of SHRSP rats.

Animals↗

Raloxifene therapy.

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Accidental Falls↗

Adverse events reported by postmenopausal women in controlled trials with raloxifene.

OBJECTIVE: To assess the incidence of adverse events in postmenopausal women treated with raloxifene compared with placebo, hormone replacement therapy (HRT), or unopposed estrogen. METHODS: Common treatment groups were pooled across eight randomized, parallel clinical trials (6-30 months' duration) of raloxifene to create the following three databases: placebo-controlled, HRT-controlled, and estrogen-controlled databases. Incidence and severity of all treatment-emergent adverse events, defined as events that first occurred or worsened during treatment, were compared among groups in each of the databases. RESULTS: Discontinuation rates overall, and those related to adverse events, were not significantly different between treatment groups in any database. There was no significant difference in incidence of vaginal bleeding or breast discomfort between women treated with raloxifene (60 mg/d) or placebo. Both of these events were reported more frequently in women receiving HRT or estrogen. Vaginal bleeding was responsible for significantly more discontinuations from the HRT groups compared with the raloxifene group. Hot flashes was the only event common to all three databases that was significantly increased in the raloxifene group, but this event did not increase the discontinuation rates. The incidence of leg cramps was greater in raloxifene-treated women compared with placebo-treated women in the placebo-controlled database, but did not cause any discontinuations of therapy. Raloxifene had no effect on the incidence of vaginal symptoms or central nervous system events. CONCLUSION: Raloxifene had an adverse event profile distinct from HRT and unopposed estrogen and was well tolerated by postmenopausal women.

Adult↗

Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks.

The purpose of this study is to estimate the level of healthcare use and costs incurred by postmenopausal women overall and for these selected conditions: cardiovascular disease, osteoporosis, breast cancer, and gynecological cancers. National healthcare survey and discharge data were used to estimate healthcare use by women aged 45 and older. Clinical Classification for Health Policy Research (CCHPR) codes were used to identify patients whose primary diagnosis or procedure corresponded with the selected conditions. National weights were used to estimate resource use. Treatment costs were estimated using cost/charge ratios or the Medicare fee schedule to calculate costs for each individual procedure. Estimated total annual medical care treatment costs for women 45 and older were about $186 billion in 1997 dollars, including about $60.4 billion for cardiovascular disease, $12.9 billion for osteoporosis, and $5.0 billion for breast and gynecological cancers. For each condition, estimated resource use and costs are reported for hospitalization, outpatient, nursing home, and home healthcare services. Resource use and costs are also reported by age and expected source of payment. The economic burden of disease for conditions commonly affecting postmenopausal women is substantial. Prior research establishes that hormone replacement therapy (HRT) may be effective in reducing the burden of disease among women who continue preventive therapy for many years, but few at-risk women do so. New alternatives for prevention, such as selective estrogen receptor modulators (SERMs), may be effective in reducing the burden of disease among postmenopausal women.

Aged↗

Prostaglandin F(2alpha) induces a rapid decline in progesterone production and steroidogenic acute regulatory protein expression in isolated rat corpus luteum without altering messenger ribonucleic acid expression.

With interest in steroidogenic acute regulatory protein (StAR) involvement in the luteolytic process, we studied changes in serum progesterone levels and the concomitant expression of StAR mRNA and protein (37-, 32-, and 30-kDa forms) in postovulatory Day 7 corpora lutea (CL) isolated from rats 1 h after injection with prostaglandin F(2alpha) (PGF(2alpha), n = 6) or saline (n = 6). Serum progesterone levels were determined by RIA, StAR and beta-actin mRNA expression by Northern analysis, and StAR and beta-actin protein expression by Western analysis. Adrenal, brain, and spleen from control animals were used as positive and negative controls for StAR expression. Scanning optical densitometry measurements were standardized by dividing the signal strength from each StAR autoradiogram lane by that from the corresponding beta-actin autoradiogram lane. ANOVA was used for significance testing, with alpha set at 0.05. The 37-, 32-, and 30-kDa forms of StAR protein were expressed in all adrenal samples, whereas only the 37- and 30-kDa forms were found in CL. Serum progesterone levels and expression of the 30-kDa and 37-kDa forms of the StAR protein in CL were all found to be significantly lower in the PGF(2alpha)-treated than the saline-treated group. StAR mRNA expression was not significantly different in the saline- and PGF(2alpha)-treated rats. The rapid decline in StAR protein expression that accompanies PGF(2alpha) induced luteolysis, therefore, does not result from significant decline in mRNA expression.

Actins↗

Endometrial response to raloxifene compared with placebo, cyclical hormone replacement therapy, and unopposed estrogen in postmenopausal women.

OBJECTIVE: To determine the endometrial effects of raloxifene 60 mg/day in postmenopausal women as assessed by vaginal bleeding and endometrial thickness. DESIGN: Data from 1157 postmenopausal women were analyzed from a database consisting of four independent, double-blind, randomized, placebo-controlled trials (range = 6-30 months duration), a 24-month open-label randomized, cyclical hormone replacement therapy (HRT)-controlled trial, and a 6-month double-blind, randomized, unopposed estrogen-controlled trial. Vaginal bleeding rate was derived from self-reported adverse events collected at least every 6 months. Endometrial thickness was measured by ultrasonography at regular intervals. RESULTS: Raloxifene 60 mg/day was not significantly different from placebo with regard to the incidence of vaginal bleeding, the baseline-to-endpoint change in endometrial thickness, or the proportion of women experiencing an increase in endometrial thickness above baseline after either 12 or 24 months of therapy. Unexpected bleeding was reported significantly more frequently in the unopposed estrogen groups compared with the raloxifene group (raloxifene 60 mg/day, 0% versus estrogen, 50%; p = 0.002). A significantly greater baseline-to-endpoint increase in endometrial thickness was observed in both the HRT and estrogen groups compared with their respective raloxifene comparison group (raloxifene 60 mg/day, 0.01 +/- 2.0 mm versus HRT, 1.8 +/- 3.2; p < 0.001; raloxifene 60 mg/day, 1.1 +/- 1.7 mm versus estrogen, 7.8 +/- 3.8; p < 0.001). No cases of endometrial hyperplasia or cancer were diagnosed in the placebo or raloxifene 60 mg/day groups. Endometrial hyperplasia was diagnosed in one case in the HRT group and in two cases in the estrogen group. CONCLUSION: Raloxifene 60 mg/day for up to 30 months is not associated with vaginal bleeding or increased endometrial thickness in postmenopausal women.

Aged↗

Ovaries, androgens and the menopause: practical applications.

The ovaries are a major site of production of circulating androgens during the postmenopausal years. This includes the production of testosterone. Bilateral oophorectomy can lead to a reduction in circulating testosterone levels of nearly fifty percent. Several experimental conditions have confirmed that the postmenopausal ovarian androgen production is regulated through gonadotropins and that exogenous hormones can modulate this androgen production. The function of the postmenopausal ovaries must be considered in light of these data. This body of information introduces an important consideration in the debate over elective oophorectomy at the time of unrelated gynecologic surgery.

Adult↗

Androgen effects on the central nervous system in the postmenopausal woman.

Interest in the effects of androgens on the central nervous system (CNS) in postmenopausal women dates back to at least fifty years. The mechanisms of action of androgens on the CNS are extremely complex and multi-faceted. Much data has been accumulated in recent years that suggest a beneficial role of androgens in several aspects of CNS function. These include positive effects on mood, cognition, memory, and libido. The information continues to be preliminary in nature and requires further investigations. There is evidence of altered androgen metabolism triggered by exogenous postmenopausal estrogen therapy. While promising, the current body of evidence does not yet support the routine addition of androgens to postmenopausal hormone therapy.

Adult↗

Primary chylous vaginal discharge in a 9-year-old girl: CT-lymphangiogram and MR appearance.

Chylous reflux is a manifestation of primary or secondary lymphatic obstruction. Primary lymphatic obstruction is defined as lymphangiectasia and incompetency of lymphatic valves without an underlying cause. Lymphangiectasia resulting from trauma, neoplasm, irradiation, or inflammation characterizes secondary lymphatic obstruction. Leakage of chyle into the uterus, vagina, bladder, or rectum can occur with either primary or secondary lymphatic obstruction. We report a patient with chylous vaginal discharge, a rare presentation of primary chylous reflux syndrome. CT-lymphangiography and magnetic resonance imaging clearly depicted this disorder. To our knowledge, only 20 cases of chylous vaginal discharge have been reported previously; chylous vaginal drainage occurred in the absence of chylous uterine reflux in only three. Although this is a rare anomaly, chylous reflux should be considered in a child with chronic vaginal discharge and lower extremity swelling.

Child↗

The role of p53 tumor suppressor gene and bcl-2 protooncogene in rat corpus luteum death.

OBJECTIVE: The purpose of this study was to find out whether the mammalian corpus luteum undergoes genetically programmed cell death as evidenced by the positive or negative expression of specific biochemical markers of apoptosis (p53 and bcl-2). STUDY DESIGN: Twenty-six immature 28-day-old female Sprague-Dawley rats were given 10 IU of pregnant mare's serum gonadotropin to induce ovulation and corpus luteum formation. Corpora lutea were collected on postovulatory days 8, 10, 12, and 14 and snap-frozen immediately. Determinations of apoptotic fragmentation of deoxyribonucleic acid were performed with use of samples radiolabeled at 3'-ends with deoxynucleotide alpha-phosphorus 32-deoxycytidine triphosphate (3000 Ci/mmol). Transcription of p53 and bcl-2 was determined by Northern blot analysis of total ribonucleic acid. Protein expression of p53 and bcl-2 was determined by Western blot analysis with a monoclonal rat antibody for p53 and a polyclonal rabbit antibody for bcl-2. RESULTS: The nuclear fragmentation assay revealed formation of oligonucleosomes resulting in typical laddering of the deoxyribonucleic acid (corpus luteum) consistent with programmed cell death. Northern blot analysis of total ribonucleic acid prepared from immature (28-day-old) rat corpus luteum revealed the presence of a single p53 messenger ribonucleic acid transcript (2.1 kb) in all ages of corpus luteum studied from day 8 to day 14. Western blot analysis for p53 revealed a gradual reduction in p53 protein in corpus luteum from day 8 to day 12 until it became undetectable on day 14. Western blotting revealed expression of specific protein for bcl-2. CONCLUSIONS: It appears that programmed cell death, as evidenced by formation of oligonucleosomes, occurs during mammalian luteal regression. The patterns of p53 ribonucleic acid expression in the corpus luteum suggest that the protein products of p53 and bcl-2 do not act in a diametric manner to regulate programmed cell death in the corpus luteum. The current results suggest that the mechanisms leading to programmed cell death in the mammalian corpus luteum may differ considerably from those in other organ systems.

Animals↗