Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial. Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate. Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. [Transcutaneous electric stimulation of the brain: a comparative study of the effects of its combination with peridural anesthesia using bupivacaine-fentanyl during obstetrical analgesia]. Cognitive training in MS: effects and relation to brain atrophy. GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study. Ultrasound guidance improves the success of sciatic nerve block at the popliteal fossa. Short term treatment with Escherichia coli recombinant human granulocyte-macrophage-colony stimulating factor prior to chemotherapy for Hodgkin disease. Prospective randomized study of D-Trp6-LHRH versus buserelin in long desensitization protocols for medically assisted conception cycles.
Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study.
                This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales.
                Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group.
                BTA is significantly more effective in the treatment of ICD, with less adverse effects. Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors. Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia. In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 micro g (n = 25), 180 microg (n = 24), or 240 microg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation. The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH >or= 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240- microg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8-4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval. We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested. In order to test the effectiveness of Anesthelec (transcutaneous cranial electrical stimulation with Limoge currents) during labour and delivery, a randomized study was carried out in 120 primiparous women with extradural anaesthesia during active labor. Combination of transcutaneous cranial electrical stimulation with epidural bupivacaine administration has been showed to provide a 20% pain relief prolongation of the first bupivacaine injection. Statistical studies of drug requirement during labor, of cervical dilatation duration, of mode and duration of delivery and of analgesia quality showed no beneficial additive effect of electrical stimulation for obstetrical analgesia when extradural anaesthesia is performed. Cognitive disorders are common in MS patients without any generally recommended treatment. Recent brain imaging studies show considerable neuroplasticity for cognitive tasks in MS patients, but also brain atrophy already early in the disease progression. We explored the benefits of a home-based cognitive training program for memory and working memory functions in relapsing-remitting MS patients controlling for whole brain and central brain atrophy as covariates.
                Using a single-blinded controlled study design, 42 patients were randomised into a treatment group and a control group. Home based computer training focusing on memory and working memory was started at least 4 weeks after the discontinuation of methylprednisolone treatment and lasted for 6 weeks. Two weeks later the patients were re-investigated for their clinical and cognitive performance. We assessed also quality of life (QoL), depression and fatigue using self-rating scales.
                Training had no effect on the neurological status and on QoL or fatigue. However, the treatment group showed better verbal learning, long-delay verbal memory performance, and working memory performance. The impact of treatment on long-delay verbal memory performance was independent from the extent of brain atrophy, whereas for the other findings brain atrophy played a significant role.
                An intensive home-based cognitive training program is suitable to improve the cognitive performance of MS patients. The impact of brain atrophy on rehabilitation outcome may differ for cognitive functions. GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol.
                Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2.
                There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups.
                Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates. Real time ultrasound guidance is a recent development in the area of peripheral nerve blockade. There are limited data from prospective randomized trials comparing its efficacy to that of traditional nerve localization techniques. In the present study, we tested the hypothesis that ultrasound guidance improves the success rate of sciatic nerve block at the popliteal fossa when compared with a nerve stimulator-guided technique.
                After Institutional Research Ethics Board approval and informed consent, 74 patients undergoing elective major foot or ankle surgery were randomly assigned to receive a sciatic nerve block at the popliteal fossa guided by either ultrasonography (group US, transverse view, needle in plane approach above the sciatic nerve bifurcation), or nerve stimulation (group NS, single injection, 10 cm proximal to the knee crease). A standardized local anesthetic admixture (15 mL of 2% lidocaine with 1:200,000 epinephrine and 15 mL of 0.5% bupivacaine) was used. Sensory and motor function was assessed by a blinded observer at predetermined intervals for up to 1 hour. Block success was defined as a loss of sensation to pinprick within 30 minutes in the distribution of both tibial and common peroneal nerves.
                Group US had a significantly higher block success rate than group NS (89.2% vs. 60.6%, P = .005), while the procedure time was similar.
                Ultrasound guidance enhances the quality of popliteal sciatic nerve block compared with single injection, nerve stimulator-guided block using either a tibial or peroneal endpoint. Ultrasound guidance resulted in higher success, faster onset, and progression of sensorimotor block, without an increase in block procedure time, or complications. Granulocyte-macrophage-colony stimulating factor (GM-CSF) administration stimulates the proliferation of hemopoietic progenitors. Shortly (48-96 hours) after its discontinuation, feedback phenomena occur and the progenitor proliferation rate drops below baseline levels. As the quiescence of hyperplastic bone marrow suggests that hemopoietic cells may be refractory to the toxic effects of cytostatic drugs, the decision was made to test the hypothesis that GM-CSF given before chemotherapy may be myeloprotective.
                Fifty-six patients with newly diagnosed Stage II-IV Hodgkin disease, ages 18-77 years, were randomized to receive GM-CSF (5 microg/kg subcutaneously) or placebo from Day 7 to Day 4 before each chemotherapy administration (6 cycles of a hybrid of mechlorethamine, vincristine, procarbazine, and prednisone with doxorubicin, bleomycin, vinblastine, and dacarbazine). The treatment was considered a success if the delivery rate of chemotherapy was >90% after 3 cycles and >80% after 6 cycles.
                Thirty patients received GM-CSF and 26 placebo. The dose intensity (85.2% vs. 79.6%) and the overall success in terms of delivery rate (56.7% vs. 50%) were higher in the GM-CSF group, although these differences were not statistically significant. The neutrophil nadirs were higher in the GM-CSF group during the first three cycles and subsequently similar in both groups.
                No significant differences in terms of myelotoxicity or drug delivery were observed between the two treatment arms. Although the myeloprotective effect of the prechemotherapy administration of GM-CSF seems to be minimal, the data indicate a safe timing between GM-CSF discontinuation and further chemotherapy. Because cumulative myelotoxicity has been observed with other growth factors, given in the interval between the chemotherapy cycles, this may be relevant to the planning of rapid cycling.
                Copyright 2000 American Cancer Society. In a prospective, controlled, randomized study where two different agonists were used, we compared three different long desensitization protocols for induction of multiple follicular growth in medically assisted conception cycles. In protocol A, 30 patients were injected with buserelin twice a day for 15 days prior to ovarian stimulation until human chorionic gonadotrophin (HCG) administration. In protocol B, 30 patients were injected with a single dose of long acting Triptorelin (3.75 mg) 15 days before the ovarian stimulation onset. In protocol C, 30 patients were injected with the long acting Triptorelin 4 weeks before ovarian stimulation followed by daily administration of 0.1 mg of the same agonist until HCG injection. There was no difference in the ovarian response to exogenous gonadotrophin stimulation, except for the presence of premature luteinization in two patients in group B. A significantly higher number of mature oocytes was collected from patients with protocol A; however, the fertilization and cleavage rate demonstrated no significant difference among the three groups of patients. The ongoing pregnancy rate and the implantation rate per treatment cycle were very similar in the three study groups. When the convenience, cost and side-effects for the patient are being considered, protocol B should be selected as the first choice when the agonist is utilized for the purpose of inducing pituitary desensitization before and during ovarian stimulation.
A single injection of BtB was effective and safe for treating cervical dystonia. Long-term uncontrolled studies suggested that further injection cycles continue to work for most patients. 
Future research should explore technical factors such as the optimum treatment intervals and use of image or electromyographic guidance for administration. Other issues include service delivery, quality of life, long-term efficacy and safety, and the relative indications for BtA, BtB and other treatments such as deep brain stimulation