Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

Localized Kaposi''s sarcoma in a patient with pemphigus vulgaris

We report the case of a patient with a 13-year history of pemphigus vulgaris (PV) treated with immunosuppressive agents, prednisone and mycophenolate mofetil who had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had been previously treated with intralesional injections of steroids. The lesions were surgically removed and polymerase chain reaction (PCR) demonstrated human herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination of KS following gradual decrease of the immunosuppressive therapy. We suggest that the treatment with intralesional steroids may have influenced the local reactivation of a latent infection of the virus, determining the appearance of this localized KS.     

Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Hood versus mask nebulization in infants with evolving bronchopulmonary dysplasia in the neonatal intensive care unit.

OBJECTIVE: To compare infants' discomfort, nursing-time and caregiver preference, and assess the clinical efficiency (as a secondary outcome) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia (BPD) in the neonatal intensive care unit. STUDY DESIGN: A prospective, open, randomized, controlled crossover clinical trial. In total, 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were randomly assigned to receive their nebulized treatments either by a facemask, or by a hood for 2-3 days, and then crossover to receive the same treatments with the other technique for another 2-3 days. Infants' discomfort, nursing-time, caregiver preference and clinical efficiency were compared. RESULTS: At baseline there was no significant clinical difference between the groups. Nurse-time required for administering the hood nebulization (mean+/-s.e.m.: 1.9+/-0.1 min) was significantly shorter than the time for mask nebulization (12.0+/-0.6 min, P<0.0001). Infants' discomfort score was significantly lower (0.1+/-0.04) for hood versus mask nebulization (2.5+/-0.2, P<0.0001). Nurses and parents unequivocally preferred the hood treatment. During both mask and hood nebulization therapies (2-3 days) clinical efficiency was comparable. While both methods caused an immediate (20 min post) clinical improvement, the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization (0.62+/-0.27 versus 0.13+/-0.14, P<0.05). CONCLUSIONS: Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization.     

The Impact of Parity on Course of Labor in a Contemporary Population

Abstract: Background: Few studies have examined in depth the labor progression of multiparas to determine if there is any additional impact of being parous beyond the first birth. The objective of this study was to determine the effect of parity on labor progression in contemporary obstetric practice. Methods: Our sample consisted of all low‐risk women who delivered a term, live‐born infant from January 2002 to March 2004 at a single institution in Delaware, United States (n = 5,589). The median duration of labor by each centimeter of cervical dilation was computed for parity = 0 (n = 2,645); parity = 1 (n = 1,839); parity = 2 (n = 750); and parity = 3 + (n = 355). Results: Multiparas had a significantly faster labor progression from 4 to 10 cm (293, 300, and 313 min, respectively, for parity = 1, parity = 2, and parity = 3 +), compared with nulliparas (383 min for parity = 0), as well as a shorter second stage of labor. However, no significant differences were found in duration of the active phase or the second stage of labor among multiparas. Conclusions: Additional childbearing appears to have no effect of on the progression of labor among multiparous subgroups. The difference in duration of the active phase between nulliparas and multiparas is substantially smaller in a contemporary population. (BIRTH 33:1 March 2006)     

Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells.

Placenta is an important source of leptin during pregnancy that contributes to the high plasma leptin levels in pregnant women. Leptin and its functional receptors are synthesized in trophoblast cells that, in turn, secrete gestational hormones supporting a paracrine or autocrine role for leptin in the endocrine activity of the placenta. In the present study we examined the effect of leptin on in vitro release of gestational hormones (human chorionic gonadotropin (hCG), human placental lactogen (hPL), progesterone, estrogens and testosterone) by human term placental cells in culture. Placentas at term were obtained immediately after delivery from mothers with uncomplicated pregnancies. Progesterone, hCG, hPL, estradiol, estrone, estriol and testosterone levels were measured by different assays in culture media of cells maintained in monolayer culture after incubation for 12, 24, 48 or 72 h with leptin or placebo. Incubation with leptin did not modify hCG, hPL, progesterone, estriol and estrone secretion for any of the doses and times assayed. However, leptin led to a dose-dependent decrease in estradiol release. This effect was observed when treatment with recombinant human leptin spanned from 12 to 72 h. At this time an increase in testosterone levels was observed in leptin-treated cells versus placebo. These results indicate that leptin can be considered a gestational hormone implied in the endocrine function of the placenta, with an important role in control of the production of steroid reproductive hormones in placental cells in vitro.     

Hormone replacement therapy and bleeding disorders.

Bleeding disorders encountered during administration of hormone replacement therapy (HRT) are reviewed. The incidence of bleeding disorders is dependent on the phase of HRT and the age of the patient. In the diagnosis of these bleedings transvaginal sonography and minihysteroscopy are very important methods. Endometrial thickness can be monitored exactly by transvaginal sonography. Outpatient minihysteroscopy without anesthesia results in higher compliance to HRT after the procedure. In hormonal treatment of bleeding disorders during HRT, the sonographically supported progestogen test is very useful and can reduce endometrium thickness. Operative treatments include myoma and polyp resection as well as endometrial ablation. By these methods a high rate of bleeding-free HRT can be reached. The problem of endometrial cancer during HRT is discussed on the basis of new literature and critical statements. The review shows the importance of individual diagnostic and treatment schedules for bleeding disorders during HRT.     

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.