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Biomedical subjects

R Acharya

Publications and source records attributed to R Acharya.

35 records · Page 2Linked to original sources

Pilot study of controlled-release pilocarpine in normal subjects.

OBJECTIVES: Current systemic treatments with sialogogues for patients with xerostomia are limited because of minimal efficacy, short duration of activity, or problems with side effects. The purpose of this pilot study was an initial assessment of safety, efficacy, duration of action, multiple dose tolerance, and side effects of a controlled-release formulation of pilocarpine hydrochloride. STUDY DESIGN: Eight healthy hospitalized subjects were given 15 mg of a controlled-release pilocarpine formulation every 12 hours for three doses. Saliva and blood samples were collected at assigned intervals. Repeated measures analysis and paired t tests were used for statistical analyses. RESULTS: A significant (p < 0.05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours. Mean plasma pilocarpine concentration reached a maximum of 8.2 ng/ml at approximately 1 hour after the first dose, 11.5 ng/ml after the third dose, and declined to near baseline (0.06 ng/ml) 24 hours after the final dose. None of the participants showed evidence of adverse effects including complaints of sweating or gastrointestinal discomfort. CONCLUSIONS: A controlled-release formulation of pilocarpine may overcome the therapeutic weaknesses of current pilocarpine preparations by prolonging salivary secretion and reducing undesirable side effects.

Adult↗

Posterior occipitoaxial fusion for atlantoaxial dislocation associated with occipitalized atlas.

Between 1989 and 1994, 50 patients suffering from congenital atlantoaxial dislocation with either an assimilated atlas or a thin or deficient posterior arch of the atlas were treated with occipitocervical fusion using the technique described by Jain and colleagues in 1993 with a few modifications. An artificial bridge created from the occipital bone along the margin of the foramen magnum was fused to the axis using sublaminar wiring and interposed strut and lateral onlay bone grafts. Ten patients (20%) also underwent atlantoaxial lateral joint fusion by intraarticular instillation of bone chips. In 22 patients (44%) with irreducible dislocation, posterior fusion was preceded by transoral odontoidectomy. In seven patients (14%) with ventral compression, who showed marked clinical improvement on traction despite radiological evidence of persisting atlantoaxial dislocation, occipitocervical fusion was performed without ventral decompression. Seven patients (14%) underwent a single-stage transoral odontoidectomy and posterior fusion. There was no perioperative mortality and the osseous fusion rate was 88%. Of the 43 patients available at follow-up examination (range 3-12 months), 31 patients (72.09%) improved, seven (16.28%) remained the same, and five (11.6%) deteriorated in comparison with their preoperative status. Hence, this technique achieves a stable occipitocervical arthrodesis without supplemental external orthoses and facilitates early postoperative mobilization.

Adolescent↗

Algorithm for the automated alignment of radiographs for image subtraction.

The results of this study indicate that automated alignment of pairs of radiographs produces subtractions that are indistinguishable in quality from subtractions aligned manually by an experienced aligner. In developing the algorithm for automated alignment, care was taken that the criteria used for establishing a window appropriate for testing the quality of alignment were the same for both alignment techniques.

Algorithms↗

Methods used in the structure determination of foot-and-mouth disease virus.

The structure of foot-and-mouth disease virus (FMDV) strain O1 BFS 1860 has been determined to 2.9 A resolution using the molecular-replacement method [Acharya, Fry, Stuart, Fox, Rowlands & Brown (1989). Nature (London), 337, 709-716]. Crystals of the virus with average dimensions 0.12 x 0.06 x 0.12 mm belong to space group I23, a = 345 A with 1/12 of the icosahedral particle per asymmetric unit giving fivefold noncrystallographic redundancy. Oscillation diffraction photographs were collected at the SERC Synchrotron Radiation Source at Daresbury in accordance with strict disease security regulations. The ambiguity in particle orientation was resolved using a self-rotation function and starting estimates of the phases to 8 A were derived from the known structures of two picornaviruses similarly oriented in the I23 unit cell. The phases were refined and extended using iterative averaging and solvent flattening with the implementation of a simple automatic envelope-determination procedure to increase the phasing power available.

Aphthovirus↗

Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus.

Changes resulting in altered antigenic properties of viruses nearly always occur on their surface and have been attributed to the substitution of residues directly involved in binding antibody. To investigate the mechanism of antigenic variation in foot-and-mouth disease virus (FMDV), variants that escape neutralization by a monoclonal antibody have been compared crystallographically and serologically with parental virus. FMDVs form one of the four genera of the Picornaviridae. The unenveloped icosahedral shell comprises 60 copies each of four structural proteins VP1-4. Representatives from each of the genera have similar overall structure, but differences in the external features. For example, human rhinovirus has a pronounced 'canyon' that is proposed to contain the cell attachment site, whereas elements of the attachment site for FMDV, which involves the G-H loop (residues 134-160) and C-terminus (200-213) of VP1, are exposed on the surface. Moreover, this G-H loop, which is a major antigenic site of FMDV, forms a prominent, highly accessible protrusion, a feature not seen in other picornaviruses. It is this loop that is perturbed in the variant viruses that we have studied. The amino acid mutations characterizing the variants are not at positions directly involved in antibody binding, but result in far-reaching perturbations of the surface structure of the virus. Thus, this virus seems to use a novel escape mechanism whereby an induced conformational change in a major antigenic loop destroys the integrity of the epitope.

Antibodies, Monoclonal↗

The structure of foot-and-mouth disease virus: implications for its physical and biological properties.

The structure of foot-and-mouth disease virus has been solved at a resolution of 2.9 A by X-ray diffraction techniques. The overall structural organisation of the particle is similar to that seen in other picornaviruses but there are several unique features. Many of these help to explain its characteristic physical and biological properties. In particular the canyon or pit found at the surface of other picornaviruses is lacking, which has important implications for cell attachment and the process of infection. Also there are 60 large disordered protrusions at the surface corresponding to the major antigenic site. This disorder is of particular interest in relation to the striking ability of linear synthetic peptides to induce protective immunity against foot-and-mouth disease.

Animals↗

The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution.

The structure of foot-and-mouth disease virus has been determined at close to atomic resolution by X-ray diffraction without experimental phase information. The virus shows similarities with other picornaviruses but also several unique features. The canyon or pit found in other picornaviruses is absent; this has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface.

Algorithms↗

Visualization and interactive exploration of multidimensional confocal images.

A confocal image analysis system is developed for automatic extraction of surface representation of biological structures. A visualization system is also developed to manipulate these surface representations and to obtain morphometrical parameters and provides a powerful tool for biomedical research such as microstructural characterization, morphogenesis, cell differentiation, tissue organization, and embryo development.

3T3 Cells↗

Biomedical imaging modalities: a tutorial.

The introduction of advanced imaging technologies has improved significantly the quality of medical care available to patients. Non-invasive imaging modalities allow a physician to make increasingly accurate diagnoses and render precise and measured modes of treatment. Current uses of imaging technologies include laboratory medicine, surgery, radiation therapy, nuclear medicine, and diagnostic radiology. This paper provides an overview of most of the popular imaging modalities currently in clinical use. It is hoped that a general understanding of the modality from which an image is derived will help researchers in the subsequent analysis of the image data.

Angiography, Digital Subtraction↗

Segmentation of multidimensional cardiac images.

One of the initial steps in the analysis of three-dimensional (3D)/four-dimensional (4D) images is Segmentation, which entails partitioning the images into relevant subsets such as object and background. In this paper, we present a multidimensional segmentation algorithm to extract object surfaces from Multidimensional Cardiac Computed Tomography (CT) scans. We propose the Generalized Morphological operators for segmentation in multidimensions. A priori knowledge of the approximate location of the object surface is communicated to the algorithm via the definition of the Search Space. The algorithm uses this definition of the Search Space to obtain the Surface Candidate elements. The search space specification reduces the computational cost and increases the reliability of the detected features.

Algorithms↗

Surface matching of multimodality image volumes by a fuzzy elastic registration technique.

Multimodality image registration is useful in diagnostic imaging and treatment planning for radiation therapy. In this paper, we present a technique which registers the surfaces of two volumes acquired by different medical imaging modalities. We represent the image volumes in terms of their surface elements known as tiles. We identify the fuzzy variables, assign fuzzy membership functions to them and generate a fuzzy rule database. The fuzzy algorithm reduces the discrepancy between the two set of tiles until the surfaces are matched. In order to study the efficacy of our approach, we severely warp a simulated image and register it with its original. We register CT and MR volumes of humanoid phantom images. Finally, we present the results at the end of the article.

Algorithms↗