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Objective: Hypoactive sexual desire disorder (HSDD) in women has been viewed inaccurately by some in the medical and payer community as analogous to erectile dysfunction (ED) in men. This literature review aims to highlight the distinctions between HSDD and ED.Methods: Two systematic literature searches were conducted on the epidemiology, symptomatology and biopsychosocial outcomes of HSDD and ED. Studies published since 2007 were considered for HSDD; studies published since 2012 were considered for ED.Results: HSDD in women is primarily a central nervous system condition related to neuroendocrine factors, whereby neural pathways that regulate sexual excitation and/or inhibition appear to be involved. A combination of organic and psychogenic factors often contributes to ED. HSDD and ED are associated with similar psychological and interpersonal consequences, but affect different phases of the sexual response model (desire versus arousal) and have different pathophysiologies, therefore requiring different treatment and outcome paradigms. ED is measured by objective, physiological responses (erection and sexual function), but quantitative assessments for HSDD are more difficult because loss of desire with associated distress has to be assessed. Outcome measures used to assess ED, such as the number of satisfying sexual events, are far less informative as an endpoint for randomized clinical trials of treatments for HSDD.Conclusions: HSDD and ED are distinct conditions affecting different phases of the sexual response model, and thus require clear and unique clinical characterization and adequate communication between the health care professional and patient for appropriate diagnosis, management and treatment.

Objective To evaluate the association between exposure to oral corticosteroids and future healthcare resource utilization and costs for patients with systemic lupus erythematosus. Methods Adults diagnosed with systemic lupus erythematosus (index date) between 1 January 2008 and 30 June 2013 and naive to oral corticosteroids with continuous health plan enrollment for ≥6 months pre- and ≥5 years post-index were identified from a large health plan claims database. Per-patient monthly average daily dose of oral corticosteroids (prednisone or its equivalent) was calculated for the first 2 years post-index to categorize patients into four steroid exposure cohorts: low (≤5 mg/day), medium (6–20 mg/day), high (>20 mg/day) and no steroids. Differences in healthcare resource utilization and total healthcare costs during the third year post-index across corticosteroid exposure cohorts were modeled with adjustment for baseline characteristics. Results The study included 18,618 systemic lupus erythematosus patients (163 high dose, 1127 medium dose, 6717 low dose and 10,611 no steroids). Compared to low-dose corticosteroid users, high-dose corticosteroid users were more likely to have emergency room visits (39.3% vs. 29.7%; p = 0.0085) and to be hospitalized (21.5% vs. 12.3%; p = 0.0005). After adjustment for baseline characteristics, they also had significantly greater average annual total healthcare costs (US$60,366 vs. US$18,777; p Conclusion Long-term high-dose oral corticosteroid use was associated with significantly greater future healthcare resource utilization and costs. Judicious reduction in daily steroid dose may decrease the imminent economic burden associated with high-dose steroid use in systemic lupus erythematosus.

Summary Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease-specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt-in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). ‘Child's pain’ was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by ‘emotional stress’ (2.67), ‘financial’ (2.40), ‘transportation’ (2.33), ‘sacrifice’ (2.17) and ‘medical management’ (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden.

In view of the lack of sufficient data regarding the morphology of the cystic duct and the extensive focus on the gallbladder, a preliminary examination of the cystic duct response to female sex steroid treatment was conducted to follow up a detailed ultrastructural study of the gallbladder epithelial response to a similar treatment. As observed in the gallbladder epithelium, the cystic duct epithelial cells of nulliparous Syrian hamsters demonstrate morphologic changes in response to female sex steroid treatment. Control (C) cystic duct epithelial cells are covered by short microvilli and each cell appears to exhibit a single vestigial cilium. Estrogen (E)- and estrogen + medroxyprogesterone (E + MP)-treatments induce differential duct cell morphologic changes. These changes are the result of steroid treatments in the significant decreasing sequence E > E + MP > C for nuclear volume, indentations and perinuclear lysosomal/lipofuscin bodies. Moreover E + MP-treatment results in larger cytoplasmic volume and more sloughing of apical cell excrescences than following E treatment. It is suggested that, similar to that in the gallbladder, the action of progestin is paramount in favoring cytoplasmic morphological changes in the cystic duct which, along with the alteration of mucus, cell sloughing, decreased bile acids and motility could also participate in the gallstone nucleation process as they are brought into the gallbladder with the incoming bile flow.

Ovariectomized Syrian hamsters treated by female sex steroids during a 1-month period show gallbladder surface epithelial changes in the fundic area consistent with apical bulging and decapitations of the epithelial cells. These events were detected in the infundibulum and the fundic or body regions of estrogen- and estrogen + progesterone-treated hamsters. In control hamsters, these events were restricted to the region in the vicinity of the bile duct. Following steroid treatment, intraluminal deposits detected resembled Ca-bilirubinate deposits described in previous studies while decapitations are similar to endometrial epithelium changes associated with hormonal physiological changes or treatments. Moreover some small electrondense deposits are comparable to those found in human cholesterol gallstones. This report indicates that, besides an alteration in bile composition, cell fragments originating from the surface epithelium of the bile duct and/or of the gallbladder mucosal epithelium could participate in gallstone nucleation.

To evaluate the efficacy of an interventional regime to reduce the perinatal mode of transmission of human immunodeficiency virus (HIV).Prospective.Perinatal HIV clinic at a university affiliated maternity hospital.After adequate counseling, consenting HIV positive women were offered perinatal intervention: (i) administration of 400 mg of zidovudine (AZT) per day for the last 6 weeks of the antenatal period; (ii) delivery by elective Caesarian section before rupture of membrances; (iii) oral AZT powder in the dose of 8 mg per kilogram daily to the infant for the first 6 weeks of life; and (iv) avoidance of breast milk. The infants were scheduled for regular follow-up for at least 18 months. A definitive diagnosis of infectivity in the infant was ascertained by two positive enzyme-linked immunosorbent assays (ELISA) at the age of 9 months and between 15 to 18 months.Of the 107 mother-infant pairs enrolled, 22 infants were lost to follow-up, 15 were under 18 months of age at the time of this analysis and 2 infants died without a diagnosis. Of the remaining 68 infants followed up, 4 tested HIV positive at 18 months. Of the 229 women-infant pairs who did not receive perinatal intervention, 55 infants followed up to 15-18 months were found to be infected.This interventional strategy significantly reduced the mother to child transmission of HIV. However, the results need to be substantiated by larger studies.

This report reviews previously published studies from our laboratory and shows some recent morphological data obtained with scanning and transmission electron microscopy regarding gallstone formation and alteration of the gallbladder epithelium in the Syrian hamster model. Both male and female hamsters were treated with female sex steroids (estradiol alone, estradiol and medroxyprogesterone, medroxyprogesterone alone) during one month. The results show that the Syrian hamster is a good model to study bile changes, gallbladder structure changes, including gallstone formation, and the regulation of cholesterol metabolism at the molecular level. Arguments in favor of this animal model are presented and, during gallstone formation, epithelial cell changes, anionic mucus secretion, and formation of gallbladder luminal deposits can be demonstrated. Recent molecular biology observations related to the effect of female sex steroids on liver cholesterol 7 alpha-hydroxylase (CYP7) gene suggest that progestin alone or primed by estrogen down regulates CYP7 transcription and activity. In addition, progesterone in cell culture systems has been shown to enhance intracellular accumulation of free cholesterol by increasing its uptake and synthesis and by decreasing its esterification by inhibiting the activity of acylcoenzyme A: cholesterol acyltransferase. Non-esterified cholesterol is free to migrate to the extracellular spaces and may contribute to nucleation within the bile. It is suggested that these effects of progesterone on cholesterol metabolism combined with the CYP7 gene down regulation, physical changes in the mucus and the hypomotility of the gallbladder and biliary ducts result in hypersaturation of cholesterol in the bile which favors gallstone formation.

The primary objective of this research project was to study the role of sex steroids in the pathogenesis of cholelithiasis using the Syrian hamster as a model. In addition to the morphological examination of the gallbladder epithelium, we thought it imperative to observe the changes induced in the biliary tract in response to the sex steroid treatment. This report focuses on the morphological changes induced in the liver. The hamsters were randomly divided into 4 groups, control (C), estrogen-treated (E), estrogen and medroxyprogesterone-treated (E+MP), and medroxyprogesterone-treated (MP) groups. The E group hepatocytes demonstrated proliferation of the smooth endoplasmic reticulum, lipofuscin-like granules, aggregates of glycogen rosettes, and dense bodies. Lipid droplets in the hepatocyte cytoplasm as well as the nuclei were detected in this group. E+MP combined treatment induced an exacerbation of all the changes observed in the E group, furthermore, there appeared to be a disruption of the hepatic parenchymal architecture. The MP-treated group also exhibited the architectural changes observed in the E+MP group, but also showed sinusoidal dilation. In response to MP alone, the fatty changes in the liver appeared to be accentuated. A striking feature induced in response to MP treatment, was a focal area suggestive of adenomatous changes.

Light (LM), transmission (TEM), and scanning (SEM) electron microscopy were used to characterize morphological changes induced in the gallbladder epithelium of female Syrian hamsters in response to one-month estradiol alone (E) and estradiol with medroxyprogesterone (E + MP) treatments. TEM data were correlated with the SEM observations. Compared with control (C), E- and E + MP-treated hamsters showed significant decreases in body weight, while the liver and gallbladder, and uterus weights increased. Moreover, E treatment induced some subcellular changes (microvilli, nucleus, mitochondria, RER, glycogen, abundant apical granules). The E + MP treatment appeared to exacerbate these similar changes and, in addition, induced apical excrescences and cell shedding. Both E and E + MP gallbladders showed luminal micelles, cellular debris and crystalliths associated with mucus. Simultaneously, an increased acidification of the mucoid content of the apical granules was noticed.

Scanning (SEM), and transmission (TEM) electron microscopy were used and correlated to morphologically characterize changes induced in the gallbladder epithelium of female Syrian hamster in response to treatments with estradiol (E) alone, and estradiol with medroxyprogesterone (E + MP). Compared with control (C), the E- and E + MP-treated groups demonstrated alterations in the serum lipid profile as well as significantly decreased body weights. The liver with gallbladder weights, as well as the uterus weights, were significantly increased. Two-month E and E + MP treatment groups exhibited increased number of anionically charged apical granules, and luminal mucoid elements. Contrastingly, the three-month treatment groups demonstrated larger and more gallstone-like deposits as compared to the C and two-month E and E + MP groups. This report presents a comprehensive overview of our previous and current data, including that of other investigators in relation to the various factors and parameters involved in the cholelithiatic process.

This report is a cytometric study of the female Syrian hamster gallbladder epithelium following 1-, 2-, and 3-month administration of female sex steroids. Nulliparous, multiparous, young, old and pregnant hamsters were used in this study. A 1 month treatment with estrogen alone significantly increases the nuclear volume of the gallbladder epithelial cells, while E + P treatment significantly affects the nuclear volume only after a 2 month treatment. On the other hand, E + P and P treatments significantly increase the cell volumes as compared to the E-treated groups, this effect is most striking following the 1 month period. Prolonged sex steroid treatment (2 and 3 month) does not appear to influence the gallbladder epithelial cell and nuclear volumes as dramatically as that observed following the 1 month treatment. The nulliparous, progesterone-treated hamsters appear to have a greater cytoplasmic volume than the multiparous group and this is substantiated by the bulging apices and the luminal cellular excrescences observed with scanning and transmission electron microscopy. These observations are similar to those reported in ovariectomized hamsters (Gilloteaux et al., 1992). Further, the gallbladder epithelial cells and nuclei of the older female hamsters demonstrate an accentuated response to a 1 month sex steroid treatment as compared to the younger hamsters for the same treatment duration. These results enable us to hypothesize that changes induced by a short term sex steroid treatment participate in the gallstone nucleation process, while longer duration of the treatments contribute to progressive enlargement and accumulation of gallbladder calculi.

All the intact female Syrian hamsters treated with medroxyprogesterone (MP) for a one-month period, without dietary manipulation, display gallbladder surface epithelial changes, and intraluminal deposits. These changes include excrescences in various stages, bulging, and extrusion of material from the epithelial cells. The most striking scanning electron microscopic observations are the dramatic events, comparable to apocrine-like secretory events observed in another related study using oophorectomized hamsters. Since the hamster gallbladder does not possess mucous goblet cells, it appears that this phenomenon could be a response to the MP treatment, thus providing a larger amount of mucous product than usual with cellular material, in addition to the possible alteration in the quality of the bile following this treatment. As a result of MP treatment, intraluminal deposits were also confirmed by using light and transmission electron microscopy. In control hamsters these events were not observed, however, small blebs outlining surface epithelial cells are seen. The results in this report complement the previous studies using the male and oophorectomized Syrian hamster model subjected to similar experimental conditions. © 1993 Wiley-Liss, Inc.