The clinical pharmacology and pharmacokinetics of ulipristal acetate for the treatment of uterine fibroids.

Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA's main clinical pharmacology and pharmacokinetic (PK) properties.

ABC versus CAB for cardiopulmonary resuscitation: a prospective, randomized simulator-based trial.

Questions Under Study: After years of advocating ABC (Airway-Breathing-Circulation), current guidelines of cardiopulmonary resuscitation (CPR) recommend CAB (Circulation-Airway-Breathing). This trial compared ABC with CAB as initial approach to CPR from the arrival of rescuers until the completion of the first resuscitation cycle.

Methods: 108 teams, consisting of two physicians each, were randomized to receive a graphical display of either the ABC algorithm or the CAB algorithm.

Scientific fraud in 20 falsified anesthesia papers : detection using financial auditing methods.

Data from natural sources show counter-intuitive distribution patterns for the leading digits to the left of the decimal point and the digit 1 is observed more frequently than all other numbers. This pattern, which was first described by Newcomb and later confirmed by Benford, is used in financial and tax auditing to detect fraud. Deviations from the pattern indicate possible falsifications.

Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: a prospective randomised simulator-based trial.

Background: Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians.

A less invasive anterior intrapelvic approach for the treatment of acetabular fractures and pelvic ring injuries.

Background: The ilioinguinal approach by Letournel has fundamentally contributed to the successful treatment of acetabular fractures. Since most of the present complications arise from soft tissue structures in the inguinal part, it would be desirable to avoid the surgical dissection of this region. We have therefore developed a less invasive anterior intrapelvic approach consisting of a suprapubic access combined with the lateral window of the ilioinguinal approach.

Sodium ferric gluconate complex maintenance therapy in children on hemodialysis.

Intravenous iron therapy is recommended for children and adults who receive hemodialysis (HD) and recombinant human erythropoietin (rHuEPO). However, limited information exists on the use of any maintenance IV iron regimen in children. Therefore, we conducted a prospective, multicenter, open-label trial of maintenance therapy with sodium ferric gluconate complex (SFGC) in iron-replete pediatric HD patients receiving rHuEPO.

Sodium ferric gluconate complex therapy in anemic children on hemodialysis.

Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) frequently develop anemia. Administration of recombinant human erythropoietin (rHuEPO) is effective in managing this anemia, although the additional demand for iron often results in iron deficiency. In adult patients undergoing HD, intravenous (IV) iron administration is known to replenish iron stores more effectively than oral iron administration.

Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.

Objective: To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments.

Subjects And Methods: Between October 15 and November 6, 2001, 13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL, 10 mg) oxybutynin.

Pharmacokinetics and metabolism of transdermal oxybutynin: in vitro and in vivo performance of a novel delivery system.

Purpose: The purpose of this work was to characterize in vitro/in vivo delivery and pharmacokinetics of oxybutynin (OXY) and its active metabolite. N-desethyloxybutynin (DEO), by a novel matrix transdermal system (TDS).

Methods: Two in vivo, randomized, three-way crossover trials examined single/multiple OXY TDS doses.

Endoscopic-assisted, minimally invasive anterior pelvic ring stabilization: a new technique and case report.

This report describes the technique of endoscopic-assisted reduction and stabilization of the anterior pelvic ring with endoscopic visualization of all critical bone and soft tissue structures. Compared with the conventional ilioinguinal approach of Letournel, the endoscopic technique facilitates a reliable internal fixation of anterior pelvic ring fractures with minimal soft tissue trauma. Thus, the use of the endoscope enables us to apply the concept of minimal invasive plate osteosynthesis to the pelvis.

[Endoscopically controlled stabilization of humerus shaft fractures. The endoscope as an aid in minimally invasive osteosynthesis].

This study describes the anatomical basis of direct visualization of the radial nerve and of fracture reduction in humeral shaft nailing and reports first clinical results. Fourteen cadavers were random selected and dissected in order to determine the exact course of the radial nerve in relationship to anatomical landmarks. In individuals with a total humeral length between 25-33 cm the radial nerve was found to cross the humeral shaft exactly in the middle of the long axis of the humeral shaft.

Endoscopic access to the extremities: the principle of fascial clefts.

Technology for endoscopic surgery has developed rapidly during the last decade. Applications of endoscopic techniques to orthopaedic surgery have been made possible by the use of balloon dissectors. Balloon dissectors create an optical cavity by separating fascial layers of a constant anatomic plane called the fascial cleft.

Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers.

Purpose: To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration.

Methods: OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration.

Use of the balloon dissector in minimally invasive aesthetic and reconstructive surgery.

The use of minimally invasive surgery continues to evolve in all fields of surgery with new developments in techniques and instrumentation. One instrument that has evolved and become useful in the field of plastic surgery is the balloon dissector. The purpose of this paper is to examine the role of the balloon dissector in minimally invasive aesthetic and reconstructive plastic surgery.

Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties.

The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse; spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS), electrically-based (MES seizures in mice and rats, corneally-kindled seizures in rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic acid, quinolinic acid and strychnine). When compared to valproate, orally administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and showed a safety index one to three-fold greater.

Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats.

Background And Purpose: Cells die by one of two mechanisms, necrosis or programmed cell death. Necrosis has been implicated in stroke and occurs when the cytoplasmic membrane is compromised. Programmed cell death requires protein synthesis and often involves endonucleolytic cleavage of the cellular DNA.

Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine.

The effect of calcium channel blockers on the decrease in central tryptophan hydroxylase (TPH) activity and serotonin (5-HT) concentration induced by repeated large doses of methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA) was evaluated. Rats received four or five injections of METH (10 or 15 mg/kg) or MDMA (10 mg/kg) at 6-h intervals, and were sacrificed 18 to 20 h or 1 week after the last administration. Flunarizine (30 mg/kg) prevented the decline in cortical and neostriatal TPH activity induced by MDMA, but failed to alter the effect of METH.

[3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: in vitro characterization.

Binding of the new benzothiazepine calcium channel blocker, (+)-(2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2- (4- methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one maleate, [3H]TA-3090), was characterized and its specificity for rat myocardial benzothiazepine receptors described. Scatchard plots and nonlinear regression analysis of specific [3H]TA-3090 binding best fit a one-site binding model (Kd = 8.8 +/- 2.

Scanning microscopy of the developing vagina in postnatal gerbils.

Scanning electron microscopy of postnatally developing gerbil vagina (birth to maturity) shows that longitudinal folds form prior to transverse folds; the process of fold formation is initiated on the dorsal wall and proceeds ventrally. From days 1 to 7 postnatally, the vaginal epithelium is composed of either flat or bulging cells, depending on the vaginal region. The luminal cell surface is covered with uniform stubby microvilli and solitary cilia.

The interaction of phenylalkylamine calcium channel blockers with the 1,4-dihydropyridine binding site.

The interaction of verapamil and other phenylalkylamine calcium channel blockers with the 1,4-dihydropyridine receptor was examined. Studies characterizing the interaction and relationship between calcium channel blocking potency and binding affinity were performed in rat myocardium. The 1,4-dihydropyridines, nifedipine and nitrendipine, interacted competitively.

Studies on Ca2+ channel antagonists. 5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylpentyl isothiocyanate, a chemoaffinity ligand derived from verapamil.

Reduction of 1 (verapamil) afforded amine 2, which was converted with thiophosgene to isothiocyanate 3, a chemoaffinity ligand for Ca2+ channels. Compound 3 showed concentration-dependent negative inotropic effects in rat right myocardial ventricular strips, EC50 = (4.56 +/- 3.

Extraction, separation, and detections of 14C-diazepam and 14C-metabolites from brain tissue of mature and old rats.

A rapid method for simultaneous determination of brain concentrations of diazepam and each of its three major metabolites in brain tissue by a reverse isotope dilution procedure is presented. Radiolabeled diazepam and metabolites were extracted from brain tissue of mature and senescent rats with ethyl ether. After the ether was evaporated the benzodiazepines were separated from the residue by passing the water soluble portion through C-18 bonded-phase extraction columns.

Aging: effects on beta-carboline binding in hippocampal subfields.

The CA1 and CA4/area dentata subfields of the hippocampus in young, mature and old rats were examined for age-related change in propyl beta-carboline-3-carboxylate (PrCC) binding. 3H-PrCC bound with high affinity (Kd = 0.82 nM) to one binding site when ethyl beta-carboline-3-carboxylate was used to delineate specific binding.