Biomedical subjects

Vibha Anand

Publications and source records attributed to Vibha Anand.

6 recordsLinked to original sources

PubMed2004

Child Health Improvement through Computer Automation: the CHICA system.

Clinical guidelines are prevalent but frequently not used. Computer reminder systems can improve adherence to guidelines but have not been widely adopted. We present a computer-based decision support system that combines these elements: 1) pediatric preventive care guidelines encoded in Arden Syntax; 2) a dynamic, scannable paper user interface; and 3) a HL7-compliant interface to existing electronic medical record systems. The result is a system that both delivers "just in time" patient-relevant guidelines to physicians during the clinical encounter and accurately captures structured data from all who interact with the system. The system performs these tasks while remaining sensitive to the workflow constraints of a busy outpatient pediatric practice.

Algorithms↗

PubMed2003

Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus.

Choroideremia (CHM) is an X-linked retinal degenerative disease resulting from a lack of functional Rab Escort Protein-1 (REP-1). As a first step in developing gene-based therapies for this disease, we evaluated the feasibility of delivering functional REP-1 to defective lymphocytes and fibroblasts isolated from individuals with CHM. A recombinant adenovirus delivering the full-length human cDNA encoding REP-1 under the control of a cytomegalovirus promoter was generated. Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Using adaptive turnaround documents to electronically acquire structured data in clinical settings.

We developed adaptive turnaround documents (ATDs) to address longstanding challenges inherent in acquiring structured data at the point of care. These computer-generated paper forms both request and receive patient tailored information specifically for electronic storage. In our pilot, we evaluated the usability, accuracy, and user acceptance of an ATD designed to enrich a pediatric preventative care decision support system. The system had an overall digit recognition rate of 98.6% (95% CI: 98.3 to 98.9) and a marksense accuracy of 99.2% (95% CI: 99.1 to 99.3). More importantly, the system reliably extracted all data from 56.6% (95% CI: 53.3 to 59.9) of our pilot forms without the need for a verification step. These results translate to a minimal workflow burden to end users. This suggests that ATDs can serve as an inexpensive, workflow-sensitive means of structured data acquisition in the clinical setting.

Ambulatory Care Information Systems↗

PubMed2002

A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus.

The immune response after ocular exposure to foreign antigens varies substantially from that of a typical systemic response. Anterior chamber associated immune deviation (ACAID) has been well documented. The immune response of the subretinal space has not been studied in as much detail. Here, we characterized the immune response of the subretinal space when it encounters the antigens AdV-GFP and AAV-GFP (recombinant adenovirus or adeno-associated virus, respectively), each delivering the reporter gene encoding green fluorescent protein (GFP). Results indicate that the subretinal space possesses an immune-deviant property similar to ACAID. AdV-elicited immune responses following subretinal injections are significantly reduced compared with systemic responses elicited by intradermal injections of the same virus. Furthermore, subretinal AdV administration results in transduction of retinal pigment epithelial cells (RPE), which are the potential antigen presenting cells of the retina. This subsequently generates a population of immunosuppressive Th2-type, cytokine-secreting, splenic T cells. This response may be advantageous to the development of ocular gene therapy.

Adenoviridae↗

PubMed2002

Beta-cyclodextrin tetradecasulfate, a novel cyclic oligosaccharide, inhibits thrombus and neointimal formation after coronary vascular injury.

BACKGROUND: Neointimal formation is a major cause of restenosis after interventional vascular procedures. Beta-cyclodextrin tetradecasulfate (beta-CDT) has been shown to inhibit fibroblast growth factor activity and we hypothesized that beta-CDT would reduce intimal formation. DESIGN: Three studies were performed: (1) pharmacokinetics of oral and intravenous beta-CDT and determination of optimal dose, (2) determination of efficacy of oral and intravenous beta-CDT in reducing neointimal formation after balloon-overstretch injury and (3) determination of the effect of beta-CDT on cellular proliferation, factor Xa activity, activated clotting time, activated partial thromboplastin time and thrombus formation. METHODS: Pharmacokinetics were determined in eight domestic swine following administration of oral beta-CDT and intravenous beta-CDT at three doses each. In the efficacy study, balloon-overstretch injury of 37 pigs (69 arteries) was performed and randomized into three groups (n = 23 arteries/group): control, oral administration of 300 mg beta-CDT/kg per day or intravenous infusion of 100 mg beta-CDT/kg per day. Animals were sacrificed 14 days later. Cellular proliferation and mural thrombus were determined in six arteries/group at 5 days and endothelial coverage was evaluated at 5 and 14 days. RESULTS: Oral and intravenous beta-CDT reduced the intimal hyperplasia area normalized to injury index by 24 and 48%, respectively: control, 3.03 +/- 0.75 mm2, oral, 2.31 +/- 0.83 mm2 (P = 0.004) and intravenous, 1.67 +/- 0.73 mm2 (P = 0.0000002). beta-CDT reduced cellular proliferation (control, 55 +/- 18%, oral, 35 +/- 7%, P = 0.03 and intravenous, 30 +/- 12%, P = 0.01) and mural thrombus formation (control, 0.84 +/- 0.4 mm2, oral, 0.44 +/- 0.14 mm2, P = 0.04, intravenous, 0.42 +/- 0.09 mm2, P = 0.03). Endothelial coverage was increased in the experimental groups (P = 0.008, oral versus control, P < 0.0001, intravenous versus control). Factor Xa activity was inhibited 9-10 fold following intravenous administration while oral administration demonstrated no effect. CONCLUSIONS: Both oral and intravenous formation of beta-CDT reduced intimal hyperplasia with the greatest reduction in the intravenous group. We postulate that beta-CDT was effective by the combination of increasing endothelial coverage, reducing mural thrombus formation, inhibiting factor Xa activity and reducing cellular proliferation.

Animals↗

PubMedDate not supplied

Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI.

BACKGROUND: Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4-sulfatase (4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats. METHODS: AAV.f4S, containing the feline 4S cDNA, was delivered unilaterally to eyes of affected cats by subretinal or intravitreal injection. Contralateral eyes received AAV with the green fluorescent protein (GFP) reporter gene as control. At 2-11 months post-injection, the cats were sacrificed and the treatment effects were evaluated histologically. RESULTS: By ophthalmoscopy and histological analyses, GFP was evident as early as 4 weeks and persisted through the latest time point (11 months). Untreated and AAV.GFP-treated diseased retinas contained massively hypertrophied RPE cells secondary to accumulation of dilated lysosomal inclusions containing dermatan sulfate. MPS VI eyes treated subretinally with AAV.f4S had minimal RPE cell inclusions and, consequently, were not hypertrophied. CONCLUSIONS: AAV-mediated subretinal delivery of f4S provided correction of the disease phenotype in RPE cells of feline MPS VI, supporting the utility of AAV as a vector for the treatment of RPE-specific as well as lysosomal storage diseases.

Animals↗