Tri-state myoelectric control of bilateral upper extremity neuroprostheses for tetraplegic individuals

For the purpose of bimanual control of tetraplegic hands that have useful movement restored by a neuroprosthetic device, the use of myoelectric signals from bilateral sternoclei-domastoid muscles is proposed. Three state control has been proposed where each sternocleidomastoid controls its ipsilateral hand. Demonstration was made with spinal-cord-injured and nonspinal-cord-injured subjects providing three levels of activation that can be repeatably made with each of these muscles. The agonist and antagonist sternocleidomastoids during this command control were differentiated so that the desired hand will respond to a command. Neither normal head movements nor head position within its comfortable range of motion were shown to interfere with the proposed command. The provision of feedback was shown as important to provide robustness in the operation for the users selection of the right or left hand. The performance of spinal cord injured and noninjured persons using this controller was quantitatively measured through the completion of precision tracking tasks by the manipulation of on-screen virtual hands. All subjects were able to operate the controller with a degree of skill acceptable for completion of functional tasks with bilateral stimulated hand grasps. The sensitivity of the subjects performance to variation in controller parameters was also measured.     

Bioequivalence of a highly variable drug: an experience with nadolol

PURPOSE: To assess the bioequivalence of nadolol 40mg and 160mg tablets (Zenith-Goldline Pharmaceuticals) using Corgard 40mg and 160mg tablets (Bristol-Meyers Squibb) as reference products, to estimate the effect of food in the gastrointestinal tract on nadolol bioavailability, and to evaluate the effectiveness of standard pharmacokinetic metrics AUCt, AUC infinity, and Cmax in bioequivalence determinations. METHODS: Four bioequivalence studies were conducted as described in the FDA Guidance. Four additional studies of varying designs were conducted to establish bioequivalence of the 40mg tablet in terms of Cmax. RESULTS: Fasted and food-effect studies of the 160mg tablet clearly established bioequivalence and revealed an unexpected reduction in nadolol bioavailability from test and reference products in the presence of food. The food-effect study of the 40mg tablet (80mg dose) revealed a similar reduction in bioavailability from each product. Fasted studies of the 40mg tablet (80mg dose) established bioequivalence in terms of AUCt and AUC infinity. However, Cmax criteria proved extremely difficult to meet in the initial 40mg fasted study because of the large variability, leading to additional studies and ultimately requiring an unreasonable number of subjects. CONCLUSIONS: Final results clearly established bioequivalence of both strengths and characterized an unexpected food effect which did not appear to be formulation-related. However, the Cmax of nadolol is only slightly sensitive to absorption rate and the relatively large variability of Cmax reduces its effectiveness as a bioequivalence metric. Findings suggest that bioequivalence criteria for highly variable drugs should be reconsidered.     

Determination of antibiotics in different water compartments via liquid chromatography-electrospray tandem mass spectrometry

The mechanisms by which BCG exerts its antitumour activity remain unclear. Attachment of BCG to the bladder via FN has been shown to be an important step in initiating its antitumorigenic activity. The mechanism(s) by which BCG operates requires LAK cells, BCG-activated killer cells, T lymphocytes (CD4) helper cells and CD8 suppressor/cytotoxic cells) and monocytes. The optimal route of administration is intravesical. The efficacy of a BCG vaccine depends on the viability, dose and strain. Differences in efficacy and side-effects have not been shown between different strains. Low-dose regimens successfully protect from recurrences, with fewer side-effects. The initial schedule of BCG is a course of six instillations in 6 weeks; when the patient fails this course, two possibilities arise. The first is maintenance therapy; response rates improve but there is more local and systemic toxicity. The second is a further 6-week course, and this seems most useful in those with a sustained response to the initial treatment. The clinical response to BCG therapy can be monitored using cytokine measurements or p53 determinations. Toxicity remains a major problem in BCG treatment and triple antituberculosis combination therapy should be given for 3 months in those with severe systemic side-effects. The use of prophylactic isoniazid is not recommend to decrease side-effects. The clinical results of BCG have been good, with success rates of 58-100%, with a minimal follow-up of one year in prophylaxis. BCG seems superior to intravesical therapy, but at the cost of inducing more adverse effects. BCG is not indicated for low- and intermediate-risk patients, in whom chemotherapy is the first choice. BCG can also be used to eliminate tumour after an incomplete TUR, or in patients who are unfit for surgery, with a 60-70% success rate. The primary and best treatment for CIS is intravesical BCG; encouraging results have been reported, with success rate of 42-83% after a minimal follow-up of one year. Although currently BCG seems to be the choice for high-risk superficial TCC, many questions remain unanswered, especially about the mechanism(s) of action, the optimal dose and clinical schedule.     

A room-based diagnostic imaging system for measurement of patient setup

A room-based diagnostic x-ray imaging system for routine measurement of radiotherapy patient orientation has been developed. The system consists of a pair of room-mounted x-ray tubes and a portable imager consisting of an orthogonal pair of phosphor screens, a mirror/lens system, a CCD camera, and computer software for comparing images of the patient to reference images. Orthogonal pairs of images can be acquired quickly and with relatively little exposure, allowing correction of patient setup on a daily basis. This could limit patient setup error to the uncertainty in the measurement and repositioning processes, a potentially significant improvement over the present standard.     

Direct percutaneous transluminal coronary angioplasty in acute myocardial infarction. Predictors of short-term outcome and the impact of coronary stenting. Study Group of The Arbeitsgemeinschaft Leitender Kardiologischer Krankenhaus?rzte (ALKK)

BACKGROUND: Direct percutaneous transluminal coronary angioplasty (PTCA) is widely accepted in the treatment of acute myocardial infarction since excellent results had been reported from several small randomized trials. Less favourable results were observed in large-scale registries. In particular, the use of stents in acute myocardial infarction has become common practice without documented evidence of clinical efficacy. METHODS: Data were analysed from a registry of all consecutive percutaneous transluminal coronary angioplasty procedures from 62 centres in Germany, including 2331 direct percutaneous transluminal coronary angioplasty in acute myocardial infarction from July 1994 to April 1997. RESULTS: The overall angiographic success rate of percutaneous transluminal coronary angioplasty, defined as complete antegrade perfusion of the infarct vessel, was 87%. In-hospital mortality was 11.2%. The most important predictor of death was the presence of cardiogenic shock in 15% of patients, of whom 52% died. Mortality in patients without shock was 3.9%. Failed percutaneous transluminal coronary angioplasty was associated with a mortality of 36%. Further independent predictors of death were older age, multivessel disease, and anterior myocardial infarction. Stents were used in 4.1% of the procedures in 1994, increasing to 53% in 1997. However, this was not accompanied by improved clinical outcome. Mortality with coronary stenting was 9.9% vs 11.6% without stents (ns). CONCLUSIONS: Direct percutaneous transluminal coronary angioplasty is a valuable treatment strategy in acute myocardial infarction, although the results are less exceptional than reported from some highly specialized centres. Failed percutaneous transluminal coronary angioplasty seems to be harmful, thus outweighing much of the benefit from successful procedures. Stents did not improve the clinical outcome significantly, despite technically successful placement in 98%. Mortality from cardiogenic shock continues to be excessively high despite direct PTCA.     

Direct exposure to gallium arsenide upregulates costimulatory activity of murine macrophages

Gallium arsenide (GaAs) is an intermetallic semiconductor compound used in the electronics industry. Acute exposure of animals to GaAs systemically suppresses several immune functions while paradoxically causing inflammation at the exposure site. We investigated the effect of GaAs on costimulatory activity of murine peritoneal macrophages, 5 days after ip exposure. Costimulation by macrophages was determined by activation of CD4(+) helper T cell hybridomas to secrete interleukin-2 in the presence of immobilized monoclonal anti-CD3 antibody. Both peritoneal exudate cells (PEC) and resident peritoneal cells exposed to GaAs provided greater costimulation to the T cells than vehicle control cells. Resident peritoneal cells exposed to GaAs were also more efficient than latex bead-exposed cells, indicating that phagocytosis alone did not cause the GaAs effect. Double immunofluorescence staining and flow cytometric analysis revealed that GaAs-exposed PEC had increased cell surface expression of costimulatory B7-1 and B7-2 molecules and intracellular adhesion molecule-1 (ICAM-1) compared to controls. In addition to these molecules, resident peritoneal macrophages exposed to GaAs also expressed significantly higher levels of heat-stable antigen (HSA). Monoclonal antibodies specific for these costimulatory molecules significantly inhibited T cell activation, demonstrating that the molecules on GaAs-exposed cells were functional. In contrast, GaAs did not upregulate costimulatory molecules on splenic macrophages. These findings suggest that direct GaAs exposure improves macrophage costimulatory activity, possibly by activating the cells, which may contribute to respiratory inflammation caused by inhalation of GaAs particles.     

Transplant medications

This article discusses the medications used most commonly to keep the lung transplant patient free of rejection and infection. Medications used in the treatment of rejection are categorized by their use; therefore, the most common three- and four-drug regimens used for induction, maintenance, and treatment of rejection are discussed. The most commonly used antibacterial, antiviral, and antifungal drugs also are identified. Tables listing the characteristics of the medications are included to make it easier for the reader to quickly identify the indications, mechanisms of action, major adverse reactions, and nursing implications of these medications.     

Two-stage designs for the logistic regression model in single-agent bioassays

In this paper we focus on the use of a two-stage procedure for logistic regression that emphasizes predicting response through the use of the Q-optimality criterion. The use of D-optimality in the first stage is primarily to allow best possible parameter estimates as one enters the second stage. However, it is important to understand that there are many ways to formulate the two-stage procedure. It may involve any optimality criterion in either stage. In fact, theoretically, one need not stop at two stages. It was our intention in this paper to demonstrate the potential in the two-stage procedure in cases in which good initial parameter estimates are not available. Those investigators who are interested in the software for the two-stage procedure described here should contact Dr. William R. Myers.     

Lung capillary albumin leak in oxygen toxicity. A quantitative immunocytochemical study

Uterine leiomyomas or fibroids are common among women of reproductive age, but their biology is poorly understood. The PTH-related protein (PTHrP) has been identified in a number of sites throughout the reproductive tract. We, therefore, examined whether fibroids express PTHrP mRNA and compared their level of expression with that in normal myometrium. Total RNA prepared from fibroid tissue and corresponding normal myometrium from seven patients was examined by RNase protection analysis. In all cases, fibroid and myometrial tissue expressed PTHrP, and in six of seven cases, PTHrP expression was higher in fibroids than in normal myometrium. Cultured fibroid cells from four patients also expressed higher levels of PTHrP mRNA than corresponding cultured normal myometrial cells. Tissue extracts from eight patients and conditioned medium from cultured cells from nine patients were examined for PTHrP immunoreactivity using a two-site immunoradiometric assay. In tissue extracts and conditioned medium, the mean PTHrP concentration was significantly higher in fibroids than normal myometrium. Immunohistochemical staining of fibroid and myometrial tissue was positive for PTHrP. Finally, PTHrP-(1-34) induced a dose-dependent increase in cAMP in fibroid and myometrial cells in vitro. These findings suggest that PTHrP may have an autocrine/paracrine function in regulating myometrial physiology and may play a role in regulating fibroid growth or differentiation.