Classic Benzodiazepines Modulate the Open-Close Equilibrium in α1β2γ2L γ-Aminobutyric Acid Type A Receptors

Background: Classic benzodiazepine agonists induce their clinical effects by binding to a site on [gamma]-aminobutyric acid type A (GABAA) receptors and enhancing receptor activity. There are conflicting data regarding whether the benzodiazepine site is allosterically coupled to [gamma]-aminobutyric acid binding versus the channel open-close (gating) equilibrium. The authors tested the hypothesis that benzodiazepine site ligands modulate [alpha]1[beta]2[gamma]2L GABAA receptor gating both in the absence of orthosteric agonists and when the orthosteric sites are occupied.

Methods: GABAA receptors were recombinantly expressed in Xenopus oocytes and studied using two-microelectrode voltage clamp electrophysiology. To test gating effects in the absence of orthosteric agonist, the authors used spontaneously active GABAA receptors containing a leucine-to-threonine mutation at residue 264 on the [alpha]1 subunit. To examine effects on gating when orthosteric sites were fully occupied, they activated wild-type receptors with high concentrations of a partial agonist, piperidine-4-sulfonic acid.

Results: In the absence of orthosteric agonists, the channel activity of [alpha]1L264T[beta]2[gamma]2L receptors was increased by diazepam and midazolam and reduced by the inverse benzodiazepine agonist FG7142. Flumazenil displayed very weak agonism and blocked midazolam from further activating mutant channels. In wild-type receptors activated with saturating concentrations of piperidine-4-sulfonic acid, midazolam increased maximal efficacy.     

Comparison between traditional 2-dimensional cephalometry and a 3-dimensional approach on human dry skulls.

The cephalogram is the standard used by orthodontists to assess skeletal, dental, and soft tissue relationships. This approach, however, is based on 2-dimensional (2D) views used to analyze 3-dimensional (3D) objects. The purpose of this project was to evaluate and compare a 3D imaging system and traditional 2D cephalometry for accuracy in recording the anatomical truth as defined by physical measurements with a calibrated caliper. Thirteen skeletal landmarks were located by both radiographic methods on 9 dry human skulls. Intraclass correlation (0.995), variance (0.054 mm(2)), and standard deviation (SD) (0.237 mm) were averaged over 76 measurements and derived from precision calipers to establish these physical measurements as a reliable gold standard to make comparisons of the 2D and 3D radiographic methods. The results showed great variability of the 2D from the gold standard, with the range varying from -17.68 mm (underestimation of Gn-Zyg R) to +15.52 mm (overestimation of Zyg L-Zyg R). In contrast, the 3D method (Sculptor, Glendora, Calif) indicated a range of the SD from -3.99 (underestimation) mm to +2.96 mm (overestimation). The 3D evaluation was much more precise, within approximately 1 mm of the gold standard. These results indicate that, when the actual distance is measured on a human skull in its true dimensions of 3D space, the Sculptor program, by using a 3D method, is more precise and 4 to 5 times more accurate than the 2D approach. Evaluating distances in 3D space with a 2D image grossly exaggerates the true measure and offers a distorted view of craniofacial growth. There is an inherent problem of representing a linear measure occupying a 3D space with a 2D image.     

Neurally Augmented Sexual Function in Human Females: A Preliminary Investigation

Objective. Neurally augmented sexual function (NASF) is the production of pleasurable genital stimulation and subsequent orgasm through the application of electrical energy to provide stimulation of the spinal cord or peripheral nerves. The purpose of this paper is to demonstrate the reproducibility of this phenomenon. Materials and Methods. Eleven otherwise healthy women, ages 32–60 years, were selected for this study. Through standard techniques, quadripolar (octopolar in the final patient) leads were placed in the epidural space percutaneuously. The lead was maneuvered initially to an L1–L2 position and then repositioned based on feedback from the patient. The patients were allowed to utilize the device ad libitum for up to 9 days. Results. Successful stimulation was achieved in 91% (10/11) of patients. These women described a greater frequency in sexual activity, increased lubrication, and overall satisfaction. A smaller subset had substantial improvement in sexual function as measured by orgasmic capacity. This subset consisted of women with secondary anorgasmia. A return of orgasmic capacity was found in 80% (4/5) of patients having secondary anorgasmia with an average intensity of ≥ 3/5 while using the device. Once the device was removed, the patients returned to their previous anorgasmic status. Conclusions. Pleasurable genital stimulation of the spinal cord is a consistently reproducible phenomenon. In a subset of the population studied, improvement in orgasmic function was noted. This was noted in the group with secondary orgasmic dysfunction.     

Airborne emissions at skin surfaces: a potential biological exposure index

 Dermal exposures of methanol were administered in a clinical study designed to compare several biological indicators. Four subjects were exposed in five exposure sessions of varying length. In each session, a sequence of measurements of methanol concentrations in blood, breath, and headspace samples of air at exposed and unexposed skin were collected before and after dermal exposures. Skin headspace samples, collected in gas sampling bags, were designed to reflect equilibrium skin: air partitioning. At exposed skin, headspace samples were highly elevated for at least 8 h following exposure, indicating the presence of a methanol reservoir in skin. After exposure, methanol concentrations at exposed skin showed a rapid initial decline, then a slower first-order decrease. Methanol concentrations were clearly detectable in headspace samples at unexposed skin. Substantial transfer from exposed skin occurred due to mechanical contact and washing. When transfer was restricted, surface concentrations at unexposed skin were similar to levels in breath and were strongly correlated to methanol concentrations in blood. While results are preliminary due to the small sample sizes and several unresolved experimental issues, the simple, rapid, and noninvasive skin headspace measurements appear useful as a biological exposure indicator that clearly shows the presence and site of a dermal exposure, and measurements at unexposed skin reflect concentrations in blood. Received: 14 March 1995/Accepted: 3 November 1995     

Value of spiral CT in hemodynamically stable patients following blunt chest trauma

Introduction: Features of spiral CT (SCT) — fast scanning, dynamic injection of contrast allowing optimal vessel opacification, and supplemental multiplanar imaging — promises to provide increased accuracy in the diagnosis of acute and non acute thoracic vascular disease. Recent work demonstrating the cost effective triage of hemodynamically stable patients after blunt chest trauma for angiography based on dynamic CT findings has prompted an investigation into the accuracy of SCT in this clinical setting. Methods: A retrospective review of all patients seen in the emergency department over the period of one year for aortic, thoracic, or blunt chest trauma evaluation was performed (74 patients) and all SCT scans available were reviewed and data reformatted for optimal delineation of pathology using maximum intensity projection and multiplanar reformation. The accuracy and predictive positive and negative values of SCT were calculated with respect to angiography, surgical, and/or clinical follow up evaluation. Results: Twenty three (31%) patients went directly to angiography owing to mediastinal widening on chest film and hemodynamic instability, of which four were positive and required emergent surgery. Seven hemodynamically stable patients (9%) had noncontrast SCT owing to mediastinal widening on chest film, all of which had angiography with none having great vessel trauma. Fourty four hemodynamically stable patients (60%) had contrast enhanced SCT (ceSCT), of which five (11%) were abnormal and underwent angiography, four of these were positive for aortic damage, one for a subclavian artery laceration. Of the remaining 39 patients who had normal ceSCT; five had angiography, all of which were normal. Of the remaining 34 patients that had normal ceSCT none had adverse outcome on clinical follow-up, minimum of 12 months. Conclusion: The predictive positive value for aortic trauma of ceSCT in blunt trauma is 80%, with a predictive negative value of 100%, indicating that it is feasible for SCT to be a first line exam in blunt chest trauma in the future.     

Surgical treatment of stapes fixation

The aim of surgical treatment of a fixed stapes is to restore an as effective as possible impedance transfer of the ossicular chain and acoustic impedance of the annular ligament of the footplate, when it has lost elasticity, and this in order to achieve the best possible physiological vibration of the inner ear fluids.     

“Gallstone Hip” and Other Sequelae of Retained Gallstones.

The fate of gallstones spilled during laparoscopic cholecystostomy has been thought to be relatively benign. Recent experience and a review of the recent literature shows that this is not always the case. We report three cases of complications of retained stones and analyse the literature with regard to types of complications, time to presentation, and recommendations for managing spilled gallstones. Retained gallstones have been shown to cause adhesions in the rat and inflammatory reactions in dogs with no evidence of absorption. The average time to presentation of complications arising from retained gallstones is 27.3 weeks. Complications include: Intraabdominal abscess formation with or without abdominal wall sinus tract formation, persisting abdominal wall sinus tracts from port site abscess, subhepatic inflammatory masses, cholelithoptysis, microabscesses and granuloma formation, liver abscess and “dumbell” shaped abscess with one side of the “dumbell” forming a subcutaneous abscess. We recommend the judicious use of retrieval devices during the extraction phase of the laparoscopic cholecystectomy, diligent removal of any spilled stones and awareness of delayed postoperative pain and tenderness as a harbinger of symptomatic retained gallstones. Documentation of intraoperative gallstone spillage, volume, type of gallstones, and effort to retrieve is recommended.     

Knee arthroplasty in rheumatoid arthritis: A report from the Swedish Knee Arthroplasty Register on 4, 381 primary operations 1985-1995

The Swedish Knee Arthroplasty Register has data on 4, 381 primary operations performed 1985-1995 for rheumatoid arthritis. Of these, 192 were performed with unicompartmental prostheses and 4143 with tricompartmental. 77% were women and the mean age was 66 years. There were 126 first, 20 second, and 1 third revision in tricompartmental arthroplasties, mainly for loosening, infection and patellar problems. There were 38 first, 3 second, and 1 third revision in unicompartmental arthroplasties, mainly for progression of RA and loosening .

Cumulative revision rates (Kaplan-Meier) were calculated. Tricompartmental knees had a 10-year cumulative revision rate of 5% and uni-knees 25%. Patients treated before 1990, men and patients younger than 55 had higher revision rates than patients treated after 1990, women and older patients, respectively. Cemented tibial components resulted in lower revision rates than uncemented ones. There was no significant difference in revision rates between patellar replaced and unreplaced knees or between the 9 commonest implant types.