Leuprolide acetate reduces both in vivo and in vitro ovarian steroidogenesis in infertile women undergoing assisted reproduction

Despite the probable inhibitory effects of GnRH analogues on ovarian steroidogenesis in vitro, their association with assisted reproduction protocols shows favorable results. This suggests that there are important differences in the behaviors of these drugs when administered in vivo versus in vitro. To clarify these differences, this study was designed to analyze the effect of leuprolide acetate (LA) on ovarian steroidogenesis in women undergoing In Vitro Fertilization (IVF). A prospective, randomized open label study was conducted on 14 women (26-35 years): seven receiving only gonadotrophins (Group 1) and seven receiving gonadotrophin plus LA at 1mg/day (Group 2). The LA in vivo effect was determined with serum and follicular fluid (FF) samples and via luteinized granulosa cell cultivation (GCC), where cells were obtained during oocyte retrieval after ovarian hyperstimulation. In vitro analysis was performed via addition of LA to GCC only for Group 1 (without LA) at progressively higher concentrations (0, 10(-12), 10(-9) and 10(-6) M). In vivo, the main observation was a reduction in androgen production in Group 2, represented by lower androstenedione production in FF (G1 = 6479 +/- 3458; G2 = 3021 +/- 1119 ng/ml; p = 0.04) and a lower testosterone peak in GC at 96 h (G1 = 0.64 +/- 0.12 ng/ml; G2 = 0.50 +/- 0.19ng/ml; P = 0.02), but a higher fertilization rate (G1 = 67%; G2 = 83%; p = 0.009). in vitro, testosterone, estradiol and progesterone were also reduced by LA, even though this reduction occurred for progesterone only at the highest LA dosage (10(-6) M; 606.0 +/- 114.3 ng/ml versus 1524.0 +/- 246.5 ng/ml; p=0.02). Results show that LA reduces ovarian steroidogenesis in vivo by essentially inhibiting androgen synthesis; whereas, in vitro, ovarian steroidogenesis is reduced overall. (C) 2008 Elsevier Inc. All rights reserved.

Signs of Temporomandibular Disorders in Migraine Patients: A Prospective, Controlled Study

Objectives: To identify signs of temporomandibular disorders and cervical pain in individuals with episodic and chronic (transformed) migraine (CM), relative to controls without headaches. Methods: In this prospective, controlled, double-blind study, we examined 93 individuals divided in 3 groups: episodic migraine EM, (n= 31), CM chronic migraine (n= 34), and controls without migraine (n= 28). We recorded signs of temporomandibular disorders, and of pain in the neck, after the protocol of Helkimo (1974). We calculated the odds ratio (OR) and confidence intervals (CI) of symptoms as a function of headache status. Data from all groups were paired and compared using the chi(2) test. The level of significance was 5% in 2-tailed tests. Results: Relative to controls, participants with EM and CM were significantly more likely to have tenderness in the masticatory muscles [controls = 28%, migraine = 54%, (OR = 3.0, 95% CI = 1.1-8.9), CM = 73% (OR = 6.9, 95% CI = 2.3-21.2)], and in the temporomandibular joint [controls = 25%, migraine = 61%, (OR = 4.7, 95% CI = 1.5-14.5), CM = 61% (OR = 4.8, 95% CI = 1.6-14.5)]. They were numerically (but nonsignificantly) more likely to have limited lateral jaw movements (CM = 34%; EM = 26%; NP = 18%), joint sounds (CM = 44%; EM = 29%; NP = 28%), and tenderness in neck muscles (CM = 64%; EM = 51%; NP = 35%). Conclusion: In a tertiary care population, individuals with EM and CM are more likely to have tenderness at the temporomandibular joint and on the masticatory muscles, relative to controls. Studies are needed to investigate whether treatment of 1 disorder will improve the other.

Temporomandibular Disorders Are Differentially Associated With Headache Diagnoses A Controlled Study

Objectives: Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. Methods: The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Results: Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [ relative risk (RR) = 7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR = 4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR = 4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (P < 0.0001), migraine (P < 0.0001), and episodic tension-type headache (P < 0.05). TMD severity was also associated with headache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P = 0.001). Painful TMD (P = 0.0034) and grade of TMD pain (P < 0.001) were associated with headache frequency. Discussion: TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study

PURPOSE. To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP). METHODS. Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan. RESULTS. TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group. CONCLUSIONS. TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.) (Invest Ophthalmol Vis Sci. 2011;52:4485-4496) DOI:10.1167/iovs.10-6932

Hypoalgesic effect of the transcutaneous electrical nerve stimulation following inguinal herniorrhaphy: A randomized, controlled trial

We investigated the effect of transcutaneous electrical nerve stimulation (TENS) for inguinal herniorrhaphy postoperative pain control in a prospective, randomized, double-blinded, placebo-controlled study. Forty patients undergoing unilateral inguinal herniorrhaphy with an epidural anesthetic technique were randomly allocated to receive either active TENS or placebo TENS. Postoperative pain was evaluated using a standard 10-point numeric rating scale (NRS). Analgesic requirements were also recorded. TENS (100 Hz, strong but comfortable sensory intensity) was applied for 30 minutes through 4 electrodes placed around the incision twice, 2 and 4 hours after surgery. Pain was assessed before and after each application of TENS and 8 and 24 hours after surgery. In the group treated with active TENS, pain intensity was significantly lower 2 hours (P = .028), 4 hours (P = .022), 8 hours (P = .006), and 24 hours (P = .001) after the surgery when compared with the group that received placebo TENS. Active TENS also decreased analgesic requirements in the postoperative period when compared with placebo TENS (P = .001). TENS is thus beneficial for postoperative pain relief, after inguinal herniorrhaphy; it has no observable side effects, and the pain-reducing effect continued for at least 24 hours. Consequently, the routine use of TENS after inguinal herniorrhaphy is recommended. Perspective: This study presents the hypoalgesic effect of high-frequency TENS for postoperative pain after inguinal herniorrhaphy. This may reinforce findings from basic science showing an opioid-like effect provided by TENS, given that high-frequency TENS has been shown to activate delta-opioid receptors. (C) 2008 by the American Pain Society.

A randomized controlled trial of homeopathic treatment of weaned piglets in a commercial swine herd

Aim: To evaluate the zootechnic performance and occurrence of diarrhea in piglets in the week post-weaning comparing supplementation with sucrose saline which contained or did not contain added homeopathic medicine. Method. Animals were randomly divided into three groups of 24 piglets each. The control group did not receive any treatment. Another group received sucrose saline, and the third group received sucrose saline with homeopathic medicine added, in the period of zero to seven days post-weaning. The homeopathic treatment consisted of Echinacea angustifolia, Avena sativa, Ignatia amara, Calcarea carbonica, all 6cH. Piglets were weighed daily for weight gain or loss, and observed for diarrhea and feed intake. Results: Animals receiving sucrose saline alone and sucrose saline with homeopathy had less weight loss than control (p = 0.017, p = 0.0001 respectively). There was no statistical difference in relation to overall incidence of diarrhea or food consumption. These data suggest that the supplementation with sucrose saline with added homeopathic medicine in the first seven days post-weaning may be an useful option to reduce weight loss in weaned piglets. Homeopathy (2008) 97, 202-205.

Effects of gonadotropin-releasing hormone at initiation of the 5-d timed artificial insemination (AI) program and timing of induction of ovulation relative to AI on ovarian dynamics and fertility of dairy heifers

Two experiments evaluated the effects of the first GnRH injection of the 5-d timed artificial insemination (AI) program on ovarian responses and pregnancy per AT (P/AI), and the effect of timing of the final GnRH to induce ovulation relative to AT on P/AI. In experiment 1, 605 Holstein heifers were synchronized for their second insemination and assigned randomly to receive GnRH on study d 0 (n = 298) or to remain as untreated controls (n = 307). Ovaries were scanned on study d 0 and 5. All heifers received a controlled internal drug-release (CIDR) insert containing progesterone on d 0, a single injection of PGF(2 alpha),, and removal of the CIDR on d 5, and GnRH concurrent with timed AT on d 8. Blood was analyzed for progesterone at AI. Pregnancy was diagnosed on d 32 and 60 after AI. Ovulation on study d 0 was greater for GnRH than control (35.4 vs. 10.6%). Presence of a new corpus luteum (CL) at PGF(2 alpha),, injection was greater for GnRH than for control (43.1 vs. 20.8%), although the proportion of heifers with a CL at PGF(2 alpha) did not differ between treatments and averaged 87.1%. Progesterone on the day of AT was greater for GaRH than control (0.50 +/- 0.07 vs. 0.28 +/- 0.07 ng/mL). The proportion of heifers at AI with progesterone <0.5 ng/mL was less for GURH than for control (73.8 vs. 88.2%). The proportion of heifers in estrus at AI did not differ between treatments and averaged 66.8%. Pregnancy per AI was not affected by treatment at d 32 or 60 (GnRH = 52.5 and 49.8% vs. control = 54.1 and 50.0%), and pregnancy loss averaged 6.0%. Responses to GnRH were not influenced by ovarian status on study d 0. In experiment 2, 1,295 heifers were synchronized for their first insemination and assigned randomly to receive a CIDR on d 0, PGF(2 alpha) and removal of the CIDR on d 5, and either GnRH 56 h after PGF(2 alpha) and AI 16 h later (OVS56, n = 644) or GnRH concurrent with AI 72 h after PGF(2 alpha) (COS72; n = 651). Estrus at AI was greater for COS72 than for OVS56 (61.4 vs. 47.5). Treatment did not affect P/AI on d 32 in heifers displaying signs of estrus at AI, but COS72 improved P/AI compared with OVS56 (55.0 vs. 47.6%) in those not in estrus at AI. Similarly, P/AI on d 60 did not differ between treatments for heifers displaying estrus, but COS72 improved P/AI compared with OVS56 (53.0 vs. 44.7%) in those not in estrus at AI. Administration of GnRH on the first day of the 5-d timed AI program resulted in low ovulation rate and no improvement in P/AI when heifers received a single PGF(2 alpha) injection 5 d later. Moreover, extending the proestrus by delaying the finAI GnRH from 56 to 72 h concurrent with AI benefited fertility of dairy heifers that did not display signs of estrus at insemination following the 5-d timed AI protocol.

Alpha lipoic acid in burning mouth syndrome - a randomized double-blind placebo-controlled trial

The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy. The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial. Thirty-eight patients (34 women and four men, median age 62.9 years, range 36-78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle. The level of reduction on burning was significant for both treatments (paired t-test: P < 0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo (t-test: P > 0.05; r = 0.75).

Effect of Smoking on Early Bone Healing Around Oxidized Surfaces: A Prospective, Controlled Study in Human Jaws

Background: This prospective and controlled histologic study evaluates the impact of smoking on bone-to-implant contact, the bone density in the threaded area, and the bone density outside the threaded area around microimplants with anodized surface retrieved from human jaws. Methods: A total of 24 subjects (mean age 51.32 +/- 7.5 years) were divided in two groups: smokers (n = 13 subjects) and non-smokers (n = 11 subjects). Each subject received one microimplant with oxidized surface during conventional mandible or maxilla implant surgery. After 8 weeks, the microimplants and the surrounding tissue were removed and prepared for histomorphometric analysis. Results: Three microimplants placed in smokers showed no osseointegration. The newly formed bone showed early stages of maturation, mainly in the non-smokers. Marginal bone loss, gap, and fibrous tissue were present around implants retrieved from smokers. Histometric evaluation indicated that the mean bone-to-implant contact ranged between 25.97% +/- 9.02% and 40.01% +/- 12.98% for smokers and non-smokers, respectively (P <0.001). Smokers presented 28.17% +/- 10.32% of bone density in the threaded area, whereas non-smokers showed 46.34% +/- 19.12%. The mean of bone density outside the threaded area ranged between 18.76% and 25.11% for smokers and non-smokers, respectively (P>0.05). Conclusion: The present data obtained in human subjects confirm that smoking has a detrimental effect on early bone tissue response around oxidized implant surfaces. J Periodontol 2010;81:575-583.

Effectiveness of 0.50% and 0.75% chlorhexidine dentifrices in orthodontic patients: A double-blind and randomized controlled trial

Introduction: In this double-blind and randomized controlled trial, we analyzed whether a lower concentration of chlorhexidine in dentifrices could reduce the risk of tooth staining without compromising its effectiveness in controlling gingivitis, bleeding, and dental plaque. Methods: Volunteers with fixed orthodontic appliances were randomly divided into 3 groups: control, 1100 ppm F, NaF (n = 27); experimental, chlorhexidine 0.50% (n = 27); and experimental, chlorhexidine 0.75% (n = 27). At baseline, and after 6 and 12 weeks, clinical examinations were carried out. Staining, calculus, gingivitis, bleeding, and dental plaque data were analyzed with Friedman tests to evaluate intragroup changes over time. To detect intergroup differences after 12 months, the data were evaluated with Kruskal-Wallis tests. Dunn tests were used in both situations for necessary post-hoc analyses. Results: The groups were statistically similar for the stain, calculus, and plaque indexes, but there were statistically significant differences for the gingival and bleeding indexes. During the experimental periods, gingivitis and bleeding scores improved in all 3 groups. Only the 0.75% chlorhexidine dentifrice significantly increased the stain index, although most patients did not notice the stains. The intergroup comparison showed a statistically significant better performance of the experimental groups regarding the gingival and bleeding indexes. Conclusions: This study suggests that the use of dentifrices with lower concentration of chlorhexidine can reduce the risk of tooth staining without compromising its effectiveness in controlling gingivitis and bleeding in orthodontic patients. (Am J Orthod Dentofacial Orthop 2009; 136: 651-6)

Pulpotomy of human primary molars with MTA and Portland cement: a randomised controlled trial

Objective This study compared the clinical and radiographic effectiveness of mineral trioxide aggregate (MTA) and Portland cement (PC) as pulp dressing agents in carious primary teeth. Methodology Thirty carious primary mandibular molars of children aged 5-9 years old were randomly assigned to MTA or PC groups, and treated by a conventional pulpotomy technique. The teeth were restored with resin modified glass ionomer cement. Clinical and radiographic successes and failures were recorded at 6, 12, 18 and 24-month follow-up. Results All pulpotomised teeth were clinically and radiographically successful at all follow-up appointments. Six out of 15 teeth in the PC group and five out of 14 teeth in the MTA group exfoliated throughout the follow-up period. No statistically significant difference regarding dentine bridge formation was found between both groups throughout the follow-up period. As far as pulp canal obliteration is concerned, a statistically significant difference was detected at 6-month follow-up (p < 0.05), since the beginning of mineralised material deposition could be radiographically detected in 100% and 57.14% of the teeth treated with PC and MTA, respectively. Conclusions PC may serve as an effective and less expensive MTA substitute in primary molar pulpotomies. Further studies and longer follow-up assessments are needed.