Biomedical subjects
W H Utian
Publications and source records attributed to W H Utian.
Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate.
OBJECTIVE: To evaluate the efficacy of lower doses of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for relieving vasomotor symptoms and vaginal atrophy. DESIGN: A randomized, double-blind, placebo-controlled trial (the Women's Health, Osteoporosis, Progestin, Estrogen study). SETTING: Study centers across the United States. PATIENT(S): Two thousand, six hundred, seventy-three healthy, postmenopausal women with an intact uterus, including an efficacy-evaluable population (n = 241 at baseline). INTERVENTION(S): Patients received for 1 year (13 cycles; in milligrams per day) CEE, 0.625; CEE, 0.625 and MPA, 2.5; CEE, 0.45; CEE, 0.45 and MPA, 2.5; CEE, 0.45 and MPA, 1.5; CEE, 0.3; CEE, 0.3 and MPA, 1.5; or placebo. MAIN OUTCOME MEASURE(S): Number and severity of hot flushes and Papanicolaou smear with vaginal maturation index (VMI) to assess vaginal atrophy. RESULT(S): In the efficacy-evaluable population, reduction in vasomotor symptoms was similar with CEE of 0.625 mg/d and MPA of 2.5 mg/d (the most commonly prescribed doses) and all lower combination doses. CEE of 0.625 mg/d alleviated hot flushes more effectively than the lower doses of CEE alone. VMI improved in all active treatment groups. CONCLUSION(S): Lower doses of CEE plus MPA relieve vasomotor symptoms and vaginal atrophy as effectively as commonly prescribed doses.
Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients. The Esclim Study Group.
OBJECTIVE: Our purpose was to evaluate the efficacy and safety of 3 dosages of Esclim, delivering 0.025 mg, 0.050 mg, or 0.100 mg 17beta-estradiol per 24 hours, in the treatment of moderate to severe vasomotor symptoms. STUDY DESIGN: In this double-blind, placebo-controlled, parallel-group, multicenter trial, 196 highly symptomatic menopausal women received 12 weeks of continuous unopposed treatment with 1 of the 3 dosages of Esclim or a matching placebo patch. RESULTS: The reduction in frequency of moderate to severe vasomotor symptoms was statistically significant compared with placebo (P <.05) from week 2 onward in the Esclim 50 and 100 groups and from week 3 onward in the Esclim 25 group. Symptom severity was also reduced. Estrogen-related adverse events, particularly metrorrhagia and endometrial hyperplasia, were less frequent in the Esclim 25 group than in the higher-dosage groups. CONCLUSION: All 3 dosages of Esclim were effective in the treatment of vasomotor symptoms. The efficacy and safety of Esclim 25 indicate a good risk-benefit ratio.
Estrogen modulates paracellular permeability of human endothelial cells by eNOS- and iNOS-related mechanisms.
Estradiol had a biphasic effect on permeability across cultures of human umbilical vein endothelial cells (HUVEC): at nanomolar concentrations it decreased the HUVEC culture permeability, but at micromolar concentrations it increased the permeability. The objective of the present study was to test the hypothesis that the changes in permeability were mediated by nitric oxide (NO)-related mechanisms. The results revealed dual modulation of endothelial paracellular permeability by estrogen. 1) An endothelial NO synthase (eNOS)-, NO-, and cGMP-related, Ca2+-dependent decrease in permeability was activated by nanomolar concentrations of estradiol, resulting in enhanced Cl- influx, increased cell size, and increases in the resistance of the lateral intercellular space (RLIS) and in the resistance of the tight junctions (RTJ); these effects appeared to be limited by the ability of cells to generate cGMP in response to NO. 2) An inducible NO synthase (iNOS)- and NO-related, Ca2+-independent increase in permeability was activated by micromolar concentrations of estradiol, resulting in enhanced Cl- efflux, decreased cell size, and decreased RLIS and RTJ. We conclude that the net effect on transendothelial permeability across HUVEC depends on the relative contributions of each of these two systems to the total paracellular resistance.
The International Menopause Society menopause-related terminology definitions.
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An historical perspective of natural and surgical menopause.
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The North American Menopause Society 1998 Menopause Survey. Part I: Postmenopausal women's perceptions about menopause and midlife.
OBJECTIVE: To collect information relevant to the mission of The North American Menopause Society (NAMS)--i.e., increasing understanding of menopause--by assessing perceptions held by postmenopausal women in the United States aged 50 to 65 years regarding their menopause transition and early postmenopausal years. DESIGN: During the period from June to July 1998, The Gallup Organization conducted 752 telephone interviews with a randomly selected sample of postmenopausal women aged 50 to 65 years from across the United States, based on questions developed by NAMS. In Part I of this survey, women were asked about their personal experiences with menopause, their health-related lifestyle changes since premenopause, their frequency of discussing menopause, and their rating of preparedness for menopause. Part II of this survey, including use of hormone replacement therapy as well as use of healthcare services, will be reported in a future communication from NAMS. RESULTS: The majority (51%) of the postmenopausal women surveyed reported being happiest and most fulfilled between the ages of 50 to 65 years, compared with when they were in their 20s (10%), 30s (17%), or 40s (16%). Many areas of their lives had improved since menopause, including family/home life, sense of personal fulfillment, ability to focus on hobbies or other interests, relationship with spouse/partner, and friendships. A majority (51%) said their sexual relationships had remained unchanged. Approximately three-quarters of women surveyed reported making some type of health-related lifestyle change, such as stopping smoking, at menopause/midlife. Women who had undergone hysterectomy expressed more improvement than women with an intact uterus, especially in the areas of sexual relationships, spouse/partner relationships, personal fulfillment, and physical health; data are not available regarding the health state of these women before surgery or whether they experienced surgical menopause, but this improvement did not appear to be the result of hormone replacement therapy. Women tended to look to women from their own generation for menopause-related information and believed that they have prepared the younger generation for menopause better than they were prepared by their mothers' generation. Those surveyed advised younger women to engage in healthful activities and become knowledgeable so that they could make informed health decisions. CONCLUSIONS: Although the postmenopausal women surveyed had differing views of menopause as well as their perceptions of postmenopause compared with premenopause, the majority viewed menopause and midlife as the beginning of many positive changes in their lives and health. Hysterectomy was a factor associated with improved sexual relationships, spouse/partner relationships, sense of personal fulfillment, and physical health.
Myths and realities of menopause.
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The North American Menopause Society develops consensus opinions.
Considerable consultation with experts in the field has led to the conclusions reached in the article entitled "NAMS Consensus Opinion." Both published literature and clinical experience were evaluated by a panel of distinguished experts who convened to prepare their recommendations for the NAMS Board of Trustees. The article may not express the only valid approach to the topic, but readers can be assured that, like all official NAMS materials, it has been drafted and reviewed with the full benefit of the Society's considerable expertise. The Society is grateful to the panelists, and to Novartis Pharmaceuticals Corporation, whose unrestricted educational grant helped to defray costs associated with the conference. We also wish to clarify that although the term "NAMS consensus" is used, one should not assume that every single member of the Society agrees with the published findings. Such a constraint would necessarily prevent any organization from publishing its opinions. The Society hopes that the advice offered will be of assistance to the many different specialists charged with providing health care for the 4,000 women (in the U.S. alone) who are reaching menopause every day. We encourage your comments. You, our readers, will determine the way that future Society opinions will be presented.
Women and menopause: beliefs, attitudes, and behaviors. The North American Menopause Society 1997 Menopause Survey.
OBJECTIVE: The main purpose in organizing this survey was to collect information relevant to The North American Menopause Society's (NAMS) educational mission and to document women's knowledge of, and attitudes toward, menopause. DESIGN: During June-July 1997, The Gallup Organization conducted 750 telephone interviews with a randomly selected sample of women 45-60 years of age from across the United States. Women were asked about their sources of information on menopause, what changes in health they anticipated as a result of menopause, why they used hormone therapy, and their attitudes toward menopause as a natural or a medical event. RESULTS: Women are more likely to believe that depression and irritability are associated with menopause than heart disease, but only a few associate menopause with an increasing vulnerability to either memory loss or Alzheimer's disease. Relief of physical symptoms of menopause was mentioned as the reason for starting hormone therapy more often than to protect against osteoporosis (25% relative to 15%), or to prevent stroke or a heart attack (10%), or to reduce the risk of developing Alzheimer's disease (2%). The single main source of women's information on menopause was a health professional (49%). The majority of women who were already menopausal or experiencing menstrual changes expressed an attitude toward menopause that was either neutral (42%) or positive (36%). CONCLUSIONS: Women are divided in their views of menopause, some seeing it as a medical condition requiring medical treatment, whereas others see it as a natural transition to be managed by "natural" means. Providing women with accurate, up-to-date information and enhancing communication between healthcare providers and menopausal women remain the challenges for NAMS.
Pieter van Keep Memorial Lecture. Menopause--a modern perspective from a controversial history.
The major milestones in the history of menopause provide a fascinating background to understanding current attitudes and prognosticating future trends in the perception and management of this event through which all women will inevitably pass. 'Menopause' is a word of multiple meanings. Once the subject of taboo; now almost in danger of overexposure. Once neglected, now recognized by multiple groups as the entry to a 'market'. The result is a new level of confusion and even exploitation in the minds of the health profession and the public alike. A historical survey of issues relating to the menopause is therefore an ideal vehicle for providing information and perspective into this fascinating and extremely important component of women's health care. One milestone on my personal historical journey is labeled 'Pieter van Keep', a time and a place where we met, forged an instant and remarkable friendship and during the course of an extraordinary day conceptualized a menopause club, ultimately the International Menopause Society (I.M.S.), a journal to become Maturitas, and an idea for enhanced quality years for women by primary preventative health care, utilizing menopause as a positive entry point. Achievement of the dream of wide scale introduction of preventive health care services to a properly informed public is certain to be as successful in reducing morbidity to older women as was the introduction years ago of proper prenatal care in reducing death and disability related to childbirth. Where we were, where we are generally and the I.M.S. specifically, and where the I.M.S. should position itself in the future is the focus of this lecture, my personal 'swan song' to the I.M.S.
Retinoids regulate tight junctional resistance of cultured human cervical cells.
The objective of the study was to determine the effect of retinoids on paracellular resistance across the cervical epithelium and the mechanisms involved. The experimental model was cultures of human CaSki cells on filters, which retain phenotypic characteristics of the endocervical epithelium. End points for paracellular resistance were measurements of transepithelial electrical resistance and fluxes of pyranine (a trisulfonic acid that traverses the epithelium via the intercellular space). Paracellular resistance was significantly increased in cells grown in retinoid-free medium; the effect could be blocked and reversed with all-trans-retinoic acid (tRA) and with agonists of RAR and RXR receptors but only partially with retinol. The effect of tRA was dose dependent and saturable, with a 50% effective concentration of 0.8 nM. The increases in paracellular resistance induced by vitamin A deficiency required longer incubation in retinoid-free medium than decreases in resistance induced by retinoic acid. tRA had only a minimal effect on paracellular resistance in cells maintained in regular medium. Retinoid-free medium increased and tRA decreased the relative cation mobility across CaSki cultures. Also the effects of tRA were nonadditive to those of cytochalasin D (which decreases tight junctional resistance) and additive to those of ionomycin (which decreases the resistance of the lateral intercellular space), suggesting that tRA modulates tight junctional resistance. It is concluded that vitamin A determines the degree of paracellular resistance across cervical cells by a mechanism that involves modulation of tight junctional resistance.
Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry.
Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.
Direction, misdirection and misconception in menopause research and management.
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Do menopause and hormonal replacement therapy influence body cell mass and body fat mass?
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Biphasic regulation of paracellular permeability in human cervical cells by two distinct nucleotide receptors.
The effects of extracellular ATP (ATPe) were characterized in human cervical cells grown on filters. ATPe changed the transepithelial conductance (GT) in a biphasic manner with an initial acute increase of 13 +/- 3% (phase I), lasting approximately 2 min, followed by a sustained decrease of 49 +/- 17% (phase II). ATPe also effected decreases of permeabilities to pyranine and to sucrose, which correspond to the phase II decrease in GT. Both phase I and II effects appear to be mediated by apical nucleotide receptors. However, the phase I effect differed from the phase II effect as follows: 1) a higher 50% effective concentration for ATPe, 22 vs. 3 microM; 2) different nucleotide specificity; 3) lack of influence of pretreatment with pertussis toxin; 4) independence from time in culture after seeding; and 5) involvement of cytosolic calcium, rather than diacylglycerol, as intracellular messenger. These differences suggest the presence of two different types of nucleotide receptors that use different intracellular signaling systems and have opposite effects on the paracellular permeability and electrical conductance. These results suggest that ATPe could regulate cervical mucus production in vivo by regulating the paracellular permeability. Depending on the specific receptors present, ATPe could either increase or decrease mucus production.
Osmolar changes regulate the paracellular permeability of cultured human cervical epithelium.
Extracellular nucleotides induce a biphasic change in the transepithelial electrical conductance (GT) of human cervical cells grown on filters: a rapid increase (phase I) followed by a sustained decrease (phase II). To probe the involvement of the intercellular space, its magnitude was varied by manipulating cell volume through changes in extracellular osmolarity. Under baseline conditions [GT = 115 mS/cm2 (approximately 9 omega.cm2)] and during phase II, hypertonic challenges resulted in an increase in GT (0.98% .mosmol-1.l-1 and 0.73%.mosmol-1.l-1, respectively). However, a hypertonic challenge during phase I decreased GT (-0.16%.mosmol-1.l-1). Hypotonic challenges decreased GT during baseline, phase I, and phase II conditions by -1%.mosmol-1.l-1. Similar trends were observed with regard to pyranine permeability. Reduction of extracellular calcium increased GT, abrogated the phase II effect of extracellular ATP, and reversed the effect of a hypertonic challenge. The additive nature of the permeability changes in response to osmotic challenges and to ATP during phase II suggests that different sites are involved in each response, i.e., the resistance of the intercellular space changes with osmolarity and that of the tight junction during phase II.
Sex hormone modulation of flow velocity in the parametrial artery of the pregnant rat.
The objective of the study was to correlate the disparate distal/proximal state of maturation of uterine segments in the rat with the hemodynamics of the parametrial uterine artery. Flow velocity was determined by the methylene blue photometric analysis. In nonpregnant animals, the velocity in the distal (VD-->P) and proximal (VP-->D) portions of the parametrial artery were similar, but in late pregnancy, VD-->P was higher than VP-->D. The difference was associated with an increased width of the distal part of the parametrial artery. In addition, the distance from the proximal end of the parametrial artery where the D-->P and P-->D streams collided decreased in animals in late pregnancy, compared with nonpregnant animals. Treatment with estradiol and RU-486 reversed the pregnancy-related hemodynamic changes. The pregnancy-related shift in flow velocity in the parametrial artery is crucial to rat fetal survival in utero and may be a mechanism in vivo for promoting maturation of distal, compared with proximal, segments of the uterine horn.